A Single Ascending Oral Dose Study of SDI-118 in Healthy Male Subjects Including an Assessment of Receptor Occupancy and Food Effect
Primary Purpose
Cognitive Disorders
Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
SDI-118
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cognitive Disorders
Eligibility Criteria
Inclusion Criteria:
- Healthy male subjects, 18 to 50 years of age, inclusive.
- Non-smokers or abstinence from tobacco for at least 3 months prior to screening.
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive, with a minimum weight of 50 kg and maximum of 100 kg.
- Venous access sufficient to allow blood sampling as per the protocol.
- Agree to abstain from alcohol intake 24h before each administration of study drug, during the in-patient period of the study and 24 hours prior to all other out-patient clinic visits.
- Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site.
- In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the clinical study protocol restrictions and requirements.
- Subjects and their partners of childbearing potential must be willing to use 2 methods of contraception, one of which must be a barrier method, for the duration of the study and up to 90 days after the last dose.
Specifically, Part B/PET related inclusion criteria:
- Adequate arterial circulation in both hands (Allen's test).
- MRI scan without clinically significant abnormalities.
Specifically, Part C/FE related inclusion criteria:
- Subjects are not vegetarian and willing to eat a standardized high fat breakfast including butter and bacon.
Exclusion Criteria:
- History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal (GI), hepatic, or renal disorder.
- Positive Hepatitis B surface antigen (HBs Ag), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
- Use of any medications (prescription or over-the-counter (OTC)), vitamin, mineral, herbal, and dietary supplements (including grapefruit products) within 7 days of study drug administration, or less than 5 half-lives (whichever is longer).
- Have an estimated Glomerular Filtration Rate (eGFR) <80 mL/min/1.73m2.
Any of the following findings in the resting ECG:
- QTcF> 450 or < 300 msec at screening or baseline visit,
- Notable resting bradycardia (HR < 40 bpm) or tachycardia (HR > 100 bpm) at screening or baseline visit,
- Personal or family history of congenital long QT syndrome or sudden death,
- Screening or baseline ECG with QRS and/or T wave judged to be unfavourable for a consistently accurate QT measurement (e.g. neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves),
- Evidence of atrial fibrillation, atrial flutter, Left Bundle Branch Block (LBBB), Wolf-Parkinson-White Syndrome, or cardiac pacemaker at screening or baseline visit (note: a first degree heart block with PR not exceeding 250 msec can be allowed).
Specifically, Part B/PET related exclusion criteria:
- Previous inclusion in a research study and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden (a significant radiation burden being defined as International Commission on Radiological Protection (ICRP) category IIb or above: no more than 1 mSv in addition to the natural background radiation in the previous 12 months including the dose from the study).
- Subject who fulfils any of the MRI contraindications on the standard radiography screening questionnaire (including the presence of ferromagnetic metal in the body or heart pacemaker).
- History of or suffers from claustrophobia or feels that they will be unable to lie still on their back in the PET camera for a period of 2 hours.
- Any known allergy to local anaesthetics or heparin.
Sites / Locations
- Centre for Clinical Pharmacology, UZ Leuven
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
SDI-118 Dose 1
SDI-118 Dose 2
SDI-118 Dose 3
SDI-118 Dose 4
SDI-118 Dose 5
SDI-118 Dose 6
SDI-118 Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of participants with Adverse Events (AEs)
Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant administered a study drug and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical product whether or not considered related to the medical product. An AE is considered "serious" if, in the view of either the investigator or sponsor, the event: results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires hospitalization or prolongation to hospitalization, or other medically important event.
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values (hematology/chemistry/urinalysis)
Number of participants with vital sign abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant vital sign values
Number of participants with temperature abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant temperature values
Number of participants with routine 12 lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant ECG values.
Number of participants with routine physical examination abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant changes in physical examination.
Number of participants with routine neurological examination abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant changes in neurological examination.
Number of participants with abnormalities on Profile of Mood States (Brief) and/or Adverse Events (AEs)
Number of participants with potentially clinically significant changes in Profile of Mood States (Brief) values.
Number of participants with abnormalities on Bond-Lader-VAS and/or Adverse Events (AEs)
Number of participants with potentially clinically significant changes in Bond-Lader VAS values.
Secondary Outcome Measures
Full Information
NCT ID
NCT05486195
First Posted
August 2, 2022
Last Updated
August 2, 2022
Sponsor
AbbVie
Collaborators
Syndesi Therapeutics, KU Leuven
1. Study Identification
Unique Protocol Identification Number
NCT05486195
Brief Title
A Single Ascending Oral Dose Study of SDI-118 in Healthy Male Subjects Including an Assessment of Receptor Occupancy and Food Effect
Official Title
A First-in-Human, Randomized, Placebo-controlled, Single Ascending Oral Dose Study of SDI-118 in Healthy Male Subjects Including Receptor Occupancy Measurements After Single Dose of SDI-118 and an Assessment of Food Effect
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
March 14, 2019 (Actual)
Primary Completion Date
July 29, 2019 (Actual)
Study Completion Date
March 11, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Syndesi Therapeutics, KU Leuven
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a First-in-Human, Randomized, Placebo-controlled, Single Ascending Oral Dose Study of SDI-118 in Healthy Male Subjects including Receptor Occupancy Measurements after Single Dose of SDI-118 and an Assessment of Food Effect.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognitive Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SDI-118 Dose 1
Arm Type
Experimental
Arm Title
SDI-118 Dose 2
Arm Type
Experimental
Arm Title
SDI-118 Dose 3
Arm Type
Experimental
Arm Title
SDI-118 Dose 4
Arm Type
Experimental
Arm Title
SDI-118 Dose 5
Arm Type
Experimental
Arm Title
SDI-118 Dose 6
Arm Type
Experimental
Arm Title
SDI-118 Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
SDI-118
Intervention Description
SDI-118 Powder in Capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching Placebo
Primary Outcome Measure Information:
Title
Number of participants with Adverse Events (AEs)
Description
Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant administered a study drug and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical product whether or not considered related to the medical product. An AE is considered "serious" if, in the view of either the investigator or sponsor, the event: results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires hospitalization or prolongation to hospitalization, or other medically important event.
Time Frame
21 Days
Title
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Description
Number of participants with potentially clinically significant laboratory values (hematology/chemistry/urinalysis)
Time Frame
21 Days
Title
Number of participants with vital sign abnormalities and/or adverse events (AEs)
Description
Number of participants with potentially clinically significant vital sign values
Time Frame
21 Days
Title
Number of participants with temperature abnormalities and/or adverse events (AEs)
Description
Number of participants with potentially clinically significant temperature values
Time Frame
21 Days
Title
Number of participants with routine 12 lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Description
Number of participants with potentially clinically significant ECG values.
Time Frame
21 Days
Title
Number of participants with routine physical examination abnormalities and/or Adverse Events (AEs)
Description
Number of participants with potentially clinically significant changes in physical examination.
Time Frame
21 Days
Title
Number of participants with routine neurological examination abnormalities and/or Adverse Events (AEs)
Description
Number of participants with potentially clinically significant changes in neurological examination.
Time Frame
21 Days
Title
Number of participants with abnormalities on Profile of Mood States (Brief) and/or Adverse Events (AEs)
Description
Number of participants with potentially clinically significant changes in Profile of Mood States (Brief) values.
Time Frame
21 Days
Title
Number of participants with abnormalities on Bond-Lader-VAS and/or Adverse Events (AEs)
Description
Number of participants with potentially clinically significant changes in Bond-Lader VAS values.
Time Frame
21 Days
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy male subjects, 18 to 50 years of age, inclusive.
Non-smokers or abstinence from tobacco for at least 3 months prior to screening.
Body mass index (BMI) between 18 and 30 kg/m2, inclusive, with a minimum weight of 50 kg and maximum of 100 kg.
Venous access sufficient to allow blood sampling as per the protocol.
Agree to abstain from alcohol intake 24h before each administration of study drug, during the in-patient period of the study and 24 hours prior to all other out-patient clinic visits.
Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site.
In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the clinical study protocol restrictions and requirements.
Subjects and their partners of childbearing potential must be willing to use 2 methods of contraception, one of which must be a barrier method, for the duration of the study and up to 90 days after the last dose.
Specifically, Part B/PET related inclusion criteria:
Adequate arterial circulation in both hands (Allen's test).
MRI scan without clinically significant abnormalities.
Specifically, Part C/FE related inclusion criteria:
Subjects are not vegetarian and willing to eat a standardized high fat breakfast including butter and bacon.
Exclusion Criteria:
History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal (GI), hepatic, or renal disorder.
Positive Hepatitis B surface antigen (HBs Ag), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
Use of any medications (prescription or over-the-counter (OTC)), vitamin, mineral, herbal, and dietary supplements (including grapefruit products) within 7 days of study drug administration, or less than 5 half-lives (whichever is longer).
Have an estimated Glomerular Filtration Rate (eGFR) <80 mL/min/1.73m2.
Any of the following findings in the resting ECG:
QTcF> 450 or < 300 msec at screening or baseline visit,
Notable resting bradycardia (HR < 40 bpm) or tachycardia (HR > 100 bpm) at screening or baseline visit,
Personal or family history of congenital long QT syndrome or sudden death,
Screening or baseline ECG with QRS and/or T wave judged to be unfavourable for a consistently accurate QT measurement (e.g. neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves),
Evidence of atrial fibrillation, atrial flutter, Left Bundle Branch Block (LBBB), Wolf-Parkinson-White Syndrome, or cardiac pacemaker at screening or baseline visit (note: a first degree heart block with PR not exceeding 250 msec can be allowed).
Specifically, Part B/PET related exclusion criteria:
Previous inclusion in a research study and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden (a significant radiation burden being defined as International Commission on Radiological Protection (ICRP) category IIb or above: no more than 1 mSv in addition to the natural background radiation in the previous 12 months including the dose from the study).
Subject who fulfils any of the MRI contraindications on the standard radiography screening questionnaire (including the presence of ferromagnetic metal in the body or heart pacemaker).
History of or suffers from claustrophobia or feels that they will be unable to lie still on their back in the PET camera for a period of 2 hours.
Any known allergy to local anaesthetics or heparin.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan deHoon, MD
Organizational Affiliation
UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Clinical Pharmacology, UZ Leuven
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Single Ascending Oral Dose Study of SDI-118 in Healthy Male Subjects Including an Assessment of Receptor Occupancy and Food Effect
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