Back to resultsA Dose-escalating Clinical Trial With KH176
Primary Purpose
MELAS, LHON, Leigh Syndrome
Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
KH176
placebo
Sponsored by
About this trial
This is an interventional treatment trial for MELAS
Eligibility Criteria
Inclusion Criteria:
- Healthy as assessed by medical history, physical examination, Vital Signs, Clinical Laboratory, ECG
Exclusion Criteria:
- Allergies,
- Concomitant medication,
- concomitant disease,
- relevant surgery,
- recent blood donation
Sites / Locations
- Drug Research Unit Ghent
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Single Escalating
Multiple Escalating
Arm Description
2 alternating groups receiving escalating single doses of active/placebo
3 multiple escalating groups, receiving active/placebo
Outcomes
Primary Outcome Measures
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Pharmacodynamics of KH176
Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD
Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
MAD: Change From Baseline in ECG Results by Time Point: QTcF
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part.
QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Phospholipidosis
Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Terminal Elimination Half-life (T1/2) of KH183: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Maximum Concentration (Cmax) of KH176: SAD Group
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.
Maximum Concentration (Cmax) of KH176: MAD
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.
Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.
Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
KH176: Percentage of Administered Dose Excreted in Urine: SAD
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
KH183: Percentage of Administered Dose Excreted in Urine: SAD
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
KH176: Percentage of Administered Dose Excreted in Urine: MAD
Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
KH183: Percentage of Administered Dose Excreted in Urine: MAD
Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD
Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Secondary Outcome Measures
Full Information
NCT ID
NCT02544217
First Posted
April 19, 2015
Last Updated
October 15, 2021
Sponsor
Khondrion BV
Collaborators
Drug Research Unit Ghent, Belgium
1. Study Identification
Unique Protocol Identification Number
NCT02544217
Brief Title
A Dose-escalating Clinical Trial With KH176
Official Title
A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Khondrion BV
Collaborators
Drug Research Unit Ghent, Belgium
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Mitochondrial Diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), Leigh's Disease and Leber's Hereditary Optic Neuropathy (LHON). KH176 is a potent intracellular redox modulating agent targeting the reactive oxygen species which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. After demonstrating a favourable safety profile in the pre-clinical testing, the safety, tolerability and pharmacokinetic and pharmacodynamic characteristics of the compound will now be evaluated in healthy male subjects in this trial
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MELAS, LHON, Leigh Syndrome, Mitochondrial Disease, Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Escalating
Arm Type
Experimental
Arm Description
2 alternating groups receiving escalating single doses of active/placebo
Arm Title
Multiple Escalating
Arm Type
Experimental
Arm Description
3 multiple escalating groups, receiving active/placebo
Intervention Type
Drug
Intervention Name(s)
KH176
Intervention Type
Drug
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Time Frame
Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up
Title
Pharmacodynamics of KH176
Description
Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group
Time Frame
Day 1, day 7
Title
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Time Frame
4 months
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)
Time Frame
Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group
Description
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD
Description
Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Title
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part.
QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Time Frame
Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
Description
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h, FU (7 days post-dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
Description
Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
Description
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time Frame
Baseline, Day 3, Day 8, FU (one week after last dosing)
Title
Phospholipidosis
Description
Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD
Time Frame
Day 1, Day 7
Title
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Time Frame
Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Title
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.
Time Frame
Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Title
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Time Frame
Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Title
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Time Frame
Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Title
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time Frame
Pre-dose, Day 1, Day 7
Title
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time Frame
Pre-dose, Day 1, Day 7
Title
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time Frame
Pre-dose, Day 1, Day 7
Title
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Description
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time Frame
Pre-dose, Day1, Day 7
Title
Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD
Description
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Terminal Elimination Half-life (T1/2) of KH183: SAD
Description
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Maximum Concentration (Cmax) of KH176: SAD Group
Description
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD
Description
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group
Description
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.
Time Frame
Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Maximum Concentration (Cmax) of KH176: MAD
Description
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time Frame
pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD
Description
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD
Description
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group
Description
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time Frame
pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group
Description
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.
Time Frame
Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group
Description
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.
Time Frame
Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group
Description
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.
Time Frame
Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group
Description
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group
Description
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:
Description
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time Frame
Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group
Description
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time Frame
Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Title
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD
Description
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD
Description
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time Frame
Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Title
KH176: Percentage of Administered Dose Excreted in Urine: SAD
Description
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
24 hours post-dose
Title
KH183: Percentage of Administered Dose Excreted in Urine: SAD
Description
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
24 hours post-dose
Title
KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD
Description
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time Frame
24 hours post-dose
Title
KH176: Percentage of Administered Dose Excreted in Urine: MAD
Description
Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time Frame
Day 7 post dose
Title
KH183: Percentage of Administered Dose Excreted in Urine: MAD
Description
Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time Frame
Post dose Day 7
Title
KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD
Description
Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time Frame
Day 7 Post dose
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy as assessed by medical history, physical examination, Vital Signs, Clinical Laboratory, ECG
Exclusion Criteria:
Allergies,
Concomitant medication,
concomitant disease,
relevant surgery,
recent blood donation
Facility Information:
Facility Name
Drug Research Unit Ghent
City
Ghent
Country
Belgium
12. IPD Sharing Statement
Citations:
PubMed Identifier
29037240
Citation
Koene S, Spaans E, Van Bortel L, Van Lancker G, Delafontaine B, Badilini F, Beyrath J, Smeitink J. KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers. Orphanet J Rare Dis. 2017 Oct 16;12(1):163. doi: 10.1186/s13023-017-0715-0.
Results Reference
derived
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A Dose-escalating Clinical Trial With KH176
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