Heart FailurePhase 1NCT03801967
A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 in Japanese Healthy Participants With Single and Multiple Ascending Dose Administration
A Phase 1 study testing AZD9977 in people with Heart Failure, run by AstraZeneca at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- What is being tested?
- AZD9977
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 24 Jan 2019to 2 May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- AZD9977, Placebo
- Keywords
- Mineralocorticoid receptor, Heart failure with preserved ejection fraction, Safety, Pharmacokinetics, Single Ascending Dose, Multiple Ascending Dose
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9977Drug
Randomized participants will receive oral dose of AZD9977.
PlaceboDrug
Randomized participants will receive oral dose of matching placebo.
| Study group | Role | What they receive |
|---|---|---|
| AZD9977 | Experimental | 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. Receives: Drug: AZD9977 |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: At week 5 (Visit 2)
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.
Measured: At week 5 (Visit 2)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: At Visit 2 (Week 5)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: At Visit 2 (Week 5)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
Measured: From screening (Day -28) till follow-up visit (Up to 6 weeks)
Secondary outcomes (21)
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2019
- Study start24 Jan 2019
- Primary completion2 May 2019
- Study completion2 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Multiple ascending dose, placebo-controlled, single blind sequential group design
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Pablo Forte Soto, MD, MSc, PhD, Principal investigator, Dr
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03801967
- Sponsor's protocol ID
- D6401C00005
- Status last verified
- May 2019
- First submitted
- 12 Dec 2018
- Last updated
- 10 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03801967
- Acronym / sponsor ID
- D6401C00005
- Conditions
- Heart Failure
- Keywords
- Mineralocorticoid receptor, Heart failure with preserved ejection fraction, Safety, Pharmacokinetics, Single Ascending Dose, Multiple Ascending Dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 24 Jan 2019 (actual)
- Primary completion
- 2 May 2019 (actual)
- Study completion
- 2 May 2019 (actual)
- First posted
- 14 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Multiple ascending dose, placebo-controlled, single blind sequential group design
| Arm | Type | Receives |
|---|---|---|
| AZD9977 | Experimental | Drug: AZD9977Each 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. |
| Placebo | Placebo comparator | Drug: PlaceboEach 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD9977Randomized participants will receive oral dose of AZD9977. | Drug | AZD9977 |
| PlaceboRandomized participants will receive oral dose of matching placebo. | Drug | Placebo |
Primary outcome
Number of participants with adverse events (AEs)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: At week 5 (Visit 2)
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)
Time frame: At week 5 (Visit 2)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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)
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: At Visit 2 (Week 5)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: At Visit 2 (Week 5)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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
Time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)
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.
21 secondary outcomes
Plasma PK analysis: Area under curve (AUC)
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
Plasma PK analysis: Maximum observed plasma concentration (Cmax)
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
Plasma PK analysis: Time to reach peak or maximum observed concentration following drug administration (tmax)
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
Plasma PK analysis: Observed concentration at the end of the dosing interval following drug administration (Cmin)
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
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)
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
Plasma PK analysis: Terminal half-life, estimated as (ln2)/λz (t½λz)
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
Plasma PK analysis: Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUClast)
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
Plasma PK analysis: Area under the plasma concentration-time curve in the dosing interval (AUCτ)
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
Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
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
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)
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
Plasma PK analysis: Mean Residence Time (MRT)
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
Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL) by λz (Vz/F)
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
Plasma PK analysis: Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUC/D)
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
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)
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
Plasma PK analysis: Area under the plasma concentration-time curve in the dosing interval divided by the dose administered (AUCτ/D)
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
Plasma PK analysis: Observed maximum plasma concentration divided by the dose administered (Cmax/D)
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
Plasma PK analysis: Accumulation ratio for AUCτ, estimated by dividing AUCτ from the last dosing day by AUCτ on Day 1 (Rac AUCτ)
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
Plasma PK analysis: Accumulation ratio for Cmax (Rac Cmax)
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
Plasma PK analysis: Temporal change, estimated by dividing AUCτ from the last dosing day by AUC on Day 1 (TCP)
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
Urine PK analysis: Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)]
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
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)%]
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pablo Forte Soto, MD, MSc, PhD principal investigator
Dr
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD9977 in people with Heart Failure, run by AstraZeneca at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) (time frame: From screening (Day -28) till follow-up visit (Up to 6 weeks)). The study lists 46 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2019.