Back to resultsA Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 in Japanese Healthy Participants With Single and Multiple Ascending Dose Administration
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
AZD9977
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Mineralocorticoid receptor, Heart failure with preserved ejection fraction, Safety, Pharmacokinetics, Single Ascending Dose, Multiple Ascending Dose
Eligibility Criteria
Inclusion Criteria:
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Agree to use the methods of contraception
- Healthy male Japanese participants aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture. A Japanese participant is defined as having both parents and 4 grandparents who are ethnically Japanese. This includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan.
- Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a participant decline to participate in the genetic and/or biomarker component of the study, there will be no penalty or loss of benefit to the participant. The participant will not be excluded from other aspects of the study described in this protocol.
Exclusion Criteria:
- History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
- History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs. 3. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
4. Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results at the Screening Visit and/or admission.
4.1. Serum potassium > 5.0 mmol/L 4.2. Hemoglobin A1c (HbA1c) > 5.7% 5. Any positive result on Screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
6. Abnormal vital signs, after 10 minutes supine rest at the Screening Visit and/or admission 7. Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiography (ECG) and any clinically important abnormalities in the 12 Lead ECG as judged by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or LV hypertrophy at the Screening Visit and/or admission.
8. Known or suspected history of drug abuse in the last 12 months before the Screening Visit as judged by the Investigator.
9. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months.
10. History of alcohol abuse in the last 12 months before the Screening Visit or current excessive intake of alcohol as judged by the Investigator.
11. Positive screen for drugs of abuse, alcohol or cotinine (nicotine) at Screening or admission.
12. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977.
13. Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate,) as judged by the Investigator.
14. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
15. Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega-dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
16. Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
17. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit, whichever is the longest. Participants consented and screened, but not randomized in this study or a previous Phase I study, are not excluded.
18. Participants who have previously received AZD9977. 19. Involvement of any Astra Zeneca or Clinical Unit employee or their close relatives.
20. Judgment by the Investigator that the participant should not participate in the study if they have any ongoing or recent (i.e., during the Screening Period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
21. Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
22. Previous bone marrow transplant. 23. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD9977
Placebo
Arm Description
Each participant will receive AZD9977 at the selected dose level on Day 1 and from Day 3 to 9, with single dose on Day 1 and Day 9 and twice a day (BID) dosing on Day 3 to Day 8. No dose will be given on Day 2.
Each participant will receive placebo at the selected dose level on Day 1 and from Day 3 to 9, with single dose on Day 1 and Day 9 and twice a day (BID) dosing on Day 3 to Day 8. No dose will be given on Day 2.
Outcomes
Primary Outcome Measures
Number of participants with adverse events (AEs)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Serious AEs will be recorded from the time of screening.
Number of participants with abnormal blood pressure (BP)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Blood pressure includes both systolic and diastolic BP.
Number of participants with abnormal supine pulse
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal findings in 12-lead safety Electrocardiogram (ECG)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal findings in 12-lead safety Digital Electrocardiogram (dECG)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal findings in Real-Time ECG (Cardiac Telemetry)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal physical examination findings
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. The complete physical examinations will include an assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
Number of participants with abnormal laboratory assessments: Hematology - absolute count of Basophils, Eosinophils, Monocytes, Neutrophils, Lymphocytes and Reticulocytes; Platelets and White blood cell (WBC) count
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assesments: Hematology - Mean corpuscular volume (MCV)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Hematology-Hematocrit (HCT)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Hematology - Hemoglobin (Hb)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Hematology - Red blood cell (RBC) count
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assesments: Heamtology - Mean corpuscular hemoglobin (MCH)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assssments : Hematology - Mean corpuscular hemoglobin concentration (MCHC)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Albumin
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Urea
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - C-reactive protein (CRP)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Alkaline phosphatase
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Alanine aminotransferase
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Aspartate aminotransferase
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Creatinine kinase
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Creatinine
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Uric acid
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Glucose (fasting)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Gamma glutamyl transpeptidase
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Phosphate
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Total Bilirubin and Unconjugated bilirubin
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Potassium
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Sodium
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Cholesterol
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Luteinizing hormone
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Triglycerides
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Sex hormone binding globulin
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Follicle-stimulating hormone
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Testosterone
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Aldosterone
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Hemoglobin A1c
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Electrolytes
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Electrolyte Measurements includes Bicarbonate, Calcium, Chloride, Potassium, Sodium
Number of participants with abnormal laboratory assessments: Clinical Chemistry - High-sensitive-CRP
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: High-sensitivity Troponin T
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: N-terminal pro-brain Natriuretic Peptide
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal urine volume
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Urinalysis - Glucose
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Urinalysis - Protein
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Number of participants with abnormal laboratory assessments: Urinalysis - Blood
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Microscopy should be done (if positive for protein or blood): red blood cells (RBC), white blood cells (WBC), Casts (Cellular, Granular, Hyaline)
Number of participants with abnorml laboratory assessments: Urinalysis - Urinary Electrolytes
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Urinary Electrolytes: Calcium, Potassium, Chloride, Sodium, Creatinine and Uric acid.
Secondary Outcome Measures
Plasma PK analysis: Area under curve (AUC)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Maximum observed plasma concentration (Cmax)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Time to reach peak or maximum observed concentration following drug administration (tmax)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Observed concentration at the end of the dosing interval following drug administration (Cmin)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve following drug administration (λz)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Terminal half-life, estimated as (ln2)/λz (t½λz)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUClast)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Area under the plasma concentration-time curve in the dosing interval (AUCτ)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Renal clearance, estimated by dividing Amount of analyte excreted into the urine(0-t) [Ae(0-t)] by AUC(0-t) where the time interval for both parameters are the same (CLr)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Mean Residence Time (MRT)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL) by λz (Vz/F)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUC/D)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration divided by the dose administered (AUClast/D)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Area under the plasma concentration-time curve in the dosing interval divided by the dose administered (AUCτ/D)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Observed maximum plasma concentration divided by the dose administered (Cmax/D)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Accumulation ratio for AUCτ, estimated by dividing AUCτ from the last dosing day by AUCτ on Day 1 (Rac AUCτ)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Accumulation ratio for Cmax (Rac Cmax)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Plasma PK analysis: Temporal change, estimated by dividing AUCτ from the last dosing day by AUC on Day 1 (TCP)
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Urine PK analysis: Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)]
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Urine PK analysis: Percentage Fraction of dose excreted in urine from time t1 to t2, estimated by dividing Ae(t1-t2) by dose * 100 [fe(t1-t2)%]
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Full Information
NCT ID
NCT03801967
First Posted
December 12, 2018
Last Updated
May 9, 2019
Sponsor
AstraZeneca
Collaborators
Parexel
1. Study Identification
Unique Protocol Identification Number
NCT03801967
Brief Title
A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 in Japanese Healthy Participants With Single and Multiple Ascending Dose Administration
Official Title
A Phase I, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 Following Single and Multiple Ascending Dose Administration in Japanese Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
January 24, 2019 (Actual)
Primary Completion Date
May 2, 2019 (Actual)
Study Completion Date
May 2, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Parexel
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
AZD9977 is an oral, selective mineralocorticoid receptor (MR) modulator. AZD9977 is a partial antagonist and partial agonist in reporter gene assays and has a different interaction pattern with the MR compared to eplerenone. This study will assess the safety, tolerability and pharmacokinetics (PK) of AZD9977, following oral administration of single and multiple ascending dose of AZD9977.
Detailed Description
This will be a Phase I, randomized, single-blind, placebo-controlled, single and multiple ascending dose sequential-group design study. The study will be conducted in healthy Japanese participants and performed at a single study center. Fourth-five healthy Japanese participants are planned to be included in the study and up to 5 additional participants may be enrolled into the study if replacement participants are needed.
Three cohorts consisting of 9 participants each will participate in the study. Depending on the findings, up to 2 additional cohorts may be added if the Safety Review Committee (SRC) considers it necessary to repeat a dose level or if additional dose steps are required.
Within each cohort, 6 participants will be randomized to receive AZD9977 and 3 participants randomized to receive placebo.
Each participant will receive AZD9977 at the selected dose level or placebo on Day 1 and from Day 3 to 9, with single dose on Day 1 and Day 9 and twice a day (BID) dosing on Day 3 to Day 8. No dose will be given on Day 2.
The study will comprise of:
A Screening Period of maximum 28 days;
A Treatment Period during which participants will be resident at the Clinical Unit from the day before Investigational Medicinal Product (IMP) administration (Day -1) until at least 48 hours after IMP administration; discharged on Day 11, and
A Follow-up Visit within 5 to 7 days after the last IMP dose. Each participant will be involved in the study for approximately 6 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Mineralocorticoid receptor, Heart failure with preserved ejection fraction, Safety, Pharmacokinetics, Single Ascending Dose, Multiple Ascending Dose
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Multiple ascending dose, placebo-controlled, single blind sequential group design
Masking
Participant
Masking Description
This study is single-blind (in which the study center staff have to remain blinded during the clinical conduct of a given cohort) with regard to treatment (AZD9977 or placebo) at each dose level. AZD9977 and placebo will be matched for formulation, appearance, and amount.
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD9977
Arm Type
Experimental
Arm Description
Each participant will receive AZD9977 at the selected dose level on Day 1 and from Day 3 to 9, with single dose on Day 1 and Day 9 and twice a day (BID) dosing on Day 3 to Day 8. No dose will be given on Day 2.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Each participant will receive placebo at the selected dose level on Day 1 and from Day 3 to 9, with single dose on Day 1 and Day 9 and twice a day (BID) dosing on Day 3 to Day 8. No dose will be given on Day 2.
Intervention Type
Drug
Intervention Name(s)
AZD9977
Intervention Description
Randomized participants will receive oral dose of AZD9977.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Randomized participants will receive oral dose of matching placebo.
Primary Outcome Measure Information:
Title
Number of participants with adverse events (AEs)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Serious AEs will be recorded from the time of screening.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal blood pressure (BP)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Blood pressure includes both systolic and diastolic BP.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal supine pulse
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal findings in 12-lead safety Electrocardiogram (ECG)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal findings in 12-lead safety Digital Electrocardiogram (dECG)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
At week 5 (Visit 2)
Title
Number of participants with abnormal findings in Real-Time ECG (Cardiac Telemetry)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
At week 5 (Visit 2)
Title
Number of participants with abnormal physical examination findings
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. The complete physical examinations will include an assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Hematology - absolute count of Basophils, Eosinophils, Monocytes, Neutrophils, Lymphocytes and Reticulocytes; Platelets and White blood cell (WBC) count
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assesments: Hematology - Mean corpuscular volume (MCV)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Hematology-Hematocrit (HCT)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Hematology - Hemoglobin (Hb)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Hematology - Red blood cell (RBC) count
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assesments: Heamtology - Mean corpuscular hemoglobin (MCH)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assssments : Hematology - Mean corpuscular hemoglobin concentration (MCHC)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Albumin
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Urea
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - C-reactive protein (CRP)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Alkaline phosphatase
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Alanine aminotransferase
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Aspartate aminotransferase
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Creatinine kinase
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Creatinine
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Uric acid
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Glucose (fasting)
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Gamma glutamyl transpeptidase
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Phosphate
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Total Bilirubin and Unconjugated bilirubin
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Potassium
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Sodium
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Cholesterol
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Luteinizing hormone
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Triglycerides
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Sex hormone binding globulin
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Follicle-stimulating hormone
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Testosterone
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Aldosterone
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Hemoglobin A1c
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - Electrolytes
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Electrolyte Measurements includes Bicarbonate, Calcium, Chloride, Potassium, Sodium
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Clinical Chemistry - High-sensitive-CRP
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
At Visit 2 (Week 5)
Title
Number of participants with abnormal laboratory assessments: High-sensitivity Troponin T
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: N-terminal pro-brain Natriuretic Peptide
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal urine volume
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
At Visit 2 (Week 5)
Title
Number of participants with abnormal laboratory assessments: Urinalysis - Glucose
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Urinalysis - Protein
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnormal laboratory assessments: Urinalysis - Blood
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Microscopy should be done (if positive for protein or blood): red blood cells (RBC), white blood cells (WBC), Casts (Cellular, Granular, Hyaline)
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Title
Number of participants with abnorml laboratory assessments: Urinalysis - Urinary Electrolytes
Description
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Urinary Electrolytes: Calcium, Potassium, Chloride, Sodium, Creatinine and Uric acid.
Time Frame
From screening (Day -28) till follow-up visit (Up to 6 weeks)
Secondary Outcome Measure Information:
Title
Plasma PK analysis: Area under curve (AUC)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Maximum observed plasma concentration (Cmax)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Time to reach peak or maximum observed concentration following drug administration (tmax)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Observed concentration at the end of the dosing interval following drug administration (Cmin)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve following drug administration (λz)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Terminal half-life, estimated as (ln2)/λz (t½λz)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUClast)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Area under the plasma concentration-time curve in the dosing interval (AUCτ)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Renal clearance, estimated by dividing Amount of analyte excreted into the urine(0-t) [Ae(0-t)] by AUC(0-t) where the time interval for both parameters are the same (CLr)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Mean Residence Time (MRT)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL) by λz (Vz/F)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUC/D)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration divided by the dose administered (AUClast/D)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Area under the plasma concentration-time curve in the dosing interval divided by the dose administered (AUCτ/D)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Observed maximum plasma concentration divided by the dose administered (Cmax/D)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Accumulation ratio for AUCτ, estimated by dividing AUCτ from the last dosing day by AUCτ on Day 1 (Rac AUCτ)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Accumulation ratio for Cmax (Rac Cmax)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Plasma PK analysis: Temporal change, estimated by dividing AUCτ from the last dosing day by AUC on Day 1 (TCP)
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Urine PK analysis: Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)]
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
Title
Urine PK analysis: Percentage Fraction of dose excreted in urine from time t1 to t2, estimated by dividing Ae(t1-t2) by dose * 100 [fe(t1-t2)%]
Description
To characterize the single and multiple dose PK of AZD9977 and assess the time required to reach steady state, the degree of accumulation and the time dependency of the PK in healthy Japanese participants.
Time Frame
Day 1-2: Pre-dose and 0-4, 4-8, 8-12 and 12-24 hours post-dose and Day 9: Pre-dose and 0-4, 4-8 and 8-12 hours post-dose
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Provision of signed and dated, written informed consent prior to any study specific procedures.
Agree to use the methods of contraception
Healthy male Japanese participants aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture. A Japanese participant is defined as having both parents and 4 grandparents who are ethnically Japanese. This includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan.
Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a participant decline to participate in the genetic and/or biomarker component of the study, there will be no penalty or loss of benefit to the participant. The participant will not be excluded from other aspects of the study described in this protocol.
Exclusion Criteria:
History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs. 3. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
4. Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results at the Screening Visit and/or admission.
4.1. Serum potassium > 5.0 mmol/L 4.2. Hemoglobin A1c (HbA1c) > 5.7% 5. Any positive result on Screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
6. Abnormal vital signs, after 10 minutes supine rest at the Screening Visit and/or admission 7. Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiography (ECG) and any clinically important abnormalities in the 12 Lead ECG as judged by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or LV hypertrophy at the Screening Visit and/or admission.
8. Known or suspected history of drug abuse in the last 12 months before the Screening Visit as judged by the Investigator.
9. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months.
10. History of alcohol abuse in the last 12 months before the Screening Visit or current excessive intake of alcohol as judged by the Investigator.
11. Positive screen for drugs of abuse, alcohol or cotinine (nicotine) at Screening or admission.
12. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977.
13. Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate,) as judged by the Investigator.
14. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
15. Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega-dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
16. Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
17. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit, whichever is the longest. Participants consented and screened, but not randomized in this study or a previous Phase I study, are not excluded.
18. Participants who have previously received AZD9977. 19. Involvement of any Astra Zeneca or Clinical Unit employee or their close relatives.
20. Judgment by the Investigator that the participant should not participate in the study if they have any ongoing or recent (i.e., during the Screening Period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
21. Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
22. Previous bone marrow transplant. 23. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pablo Forte Soto, MD, MSc, PhD
Organizational Affiliation
Dr
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Harrow
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 in Japanese Healthy Participants With Single and Multiple Ascending Dose Administration
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