Heart FailurePhase 1NCT03804645
A Study to Assess the Reaction of Body for Four Different Formulations of AZD9977 (Part A) and Influence of Food and Lower Dose of a Selected Formulation (Part B) in Healthy Male Subjects
A Phase 1 study testing Treatment A, Treatment B and Treatment C 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?
- Treatment A, Treatment B and Treatment C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Feb 2019to 16 Apr 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 subjects aged 18 to 50 years, inclusive, with suitable veins for cannulation or repeated venipuncture at screening.
- 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 at screening.
- Subject judged at screening likely to complete and agree to eat a specified high fat standardized Food and Drug Administration (FDA) breakfast.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the principal investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer'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.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI, including:
- 4.1. Serum potassium > 5.0 mmol/L.
- Any clinically significant abnormal findings in vital signs, as judged by the PI, including:
Show all 22Show fewer
- 5.1. Systolic BP < 90 mmHg or > 140 mmHg. 5.2. Diastolic BP < 50 mmHg or > 90 mmHg. 5.3. Pulse rate < 45 or > 90 beats per minute.
- Any clinically significant abnormalities on 12-lead echocardiogram (ECG), as judged by the PI.
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- Known or suspected history of drug abuse in the 12 months prior to screening, as judged by the PI.
- 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 AZD9977 in this study. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest. Note: subjects consented and screened, but not randomized in this study or a previous Phase 1 study, are not excluded.
- Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977.
- Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening.
- Positive screen for drugs of abuse, alcohol or cotinine at screening or on admission to the study center.
- Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of AZD9977.
- Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of AZD9977 or longer if the medication has a long half life.
- Known or suspected history of alcohol or drug abuse or excessive intake of alcohol in the 12 months prior to screening as judged by the PI.
- Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
- Subjects who have previously received AZD9977.
- Judgment by the PI that the subject 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.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomized, Four-way Crossover Single Oral Dose Study Comparing the Pharmacokinetics of Four Different Formulations of AZD9977 (Part A) and Influence of Food and Lower Dose of a Selected Formulation (Part B) in Healthy Male Subjects
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 pharmacokinetics (PK) of four different Formulations of AZD9977 (Part A) and influence of food and lower dose of a selected formulation (Part B) in healthy male subjects.
Read the detailed description
This study will be a randomized, open-label, single-centre crossover study in healthy male subjects. The study is divided into 2 parts, Part A and Part B. The subjects will participate in both Part A and Part B.
Part A will be a 4-way cross-over study comparing the PK of AZD9977 as a reference capsule and 2 different capsule formulations and a tablet formulation under fasting conditions.
- Treatment A: Reference, AZD9977 capsule
- Treatment B: AZD9977 HDL capsule
- Treatment C: AZD9977 ODL capsule
- Treatment D: AZD9977 tablet In Part B, based on the interim results in Part A, 1 of the formulations will be selected and evaluated at the 300 mg dose level under fed conditions. The same formulation will also be evaluated under fasting conditions at a lower dose level (50 mg). The first dose tested in Part B will be the 50 mg (fasted) dose, followed by the 300 mg (fed) dose.
In Part A, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1) with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 4). Subjects will return to the unit for Part B at least 48 hours (and up to 5 weeks) after completion of Part A.
In Part B, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1) with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 2).
Subjects will return to the unit for a final study visit 5-7 days post-last-dose for a Follow up Visit.
Each subject will be involved in the study for approximately 12 weeks (including approximately 4 to 5 weeks for the interim analysis).
Twelve subjects will initially be randomized to ensure at least 8 and 6 evaluable subjects at the end of the last treatment period for Part A and Part B respectively.
- Conditions
- Heart Failure
- Being tested
- Treatment A, Treatment B, Treatment C, Treatment D
- Keywords
- Mineralocorticoid receptor, Heart failure with preserved ejection fraction, Safety, Pharmacokinetics, Influence of Food, Bioavailability
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment ADrug
Also called AZD9977 capsule, reference
Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.
Treatment BDrug
Also called AZD9977 HDL capsule
Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.
Treatment CDrug
Also called AZD9977 ODL capsule
Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.
Treatment DDrug
Also called AZD9977 tablet
Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. Receives: Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D |
| Cohort 2 | Experimental | In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. Receives: Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D |
| Cohort 3 | Experimental | In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. Receives: Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D |
| Cohort 4 | Experimental | In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. Receives: Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D |
| Cohort 5 | Experimental | In Part B, each subject will receive one formulation from Part A chosen for further development, dose under fed conditions, followed by dose under fasted condition. Receives: Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration-time curve from time zero to infinity (AUC)
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the influence of food by comparing AUC and Cmax under fasting and fed conditions for 1 of the formulations evaluated in Part A.
Measured: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Measured: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Area under the plasma concentration-time curve from time zero to 24 hours [AUC(0-24)]
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Measured: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Maximum observed plasma concentration (Cmax)
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the influence of food by comparing AUC and Cmax under fasting and fed conditions for 1 of the formulations evaluated in Part A.
Measured: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Observed AZD9977 concentration at 24 hours (C24)
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Measured: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Area under plasma concentration-time curve from time zero to infinity divided by dose (AUC/D)
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Measured: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration divided by dose (AUClast/D)
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
Measured: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Area under the plasma concentration-time curve from time zero to 24 hours divided by dose [AUC(0-24)/D]
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
Measured: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Maximum observed plasma concentration divided by dose (Cmax/D)
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
Measured: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Observed AZD9977 concentration at 24 hours divided by dose (C24/D)
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
Measured: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
Secondary outcomes (34)
Number of subjects with Adverse events (AEs)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal blood pressure (BP)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects. Blood pressure includes both systolic and diastolic BP.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal pulse rate
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal findings in Real-Time Electrocardiogram (Cardiac Telemetry)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From Day-1 to follow-up (Week 12)
Number of subjects with abnormal findings in 12-lead safety Electrocardiogram (ECG)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal findings in physical examination
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects. The complete physical examinations will include the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: absolute count of Basophils, Eosinophils, Monocytes, Neutrophils, Lymphocytes and Reticulocytes; Platelets and White blood cell (WBC) count
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Red blood cell (RBC) count
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Hemoglobin (Hb)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Hematocrit (HCT)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Mean corpuscular volume (MCV)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Mean corpuscular hemoglobin (MCH)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Mean corpuscular hemoglobin concentration (MCHC)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry-Sodium
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry-Potassium
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Urea
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Creatinine
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Albumin
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Calcium
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Phosphate
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Glucose (fasting)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- C-reactive protein (CRP)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Alkaline phosphatase (ALP)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Alanine aminotransferase (ALT)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Aspartate aminotransferase (AST)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Gamma glutamyl transpeptidase (GGT)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Total Bilirubin (TBL)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Unconjugated bilirubin
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- High-sensitivity troponin T (hsTnT)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Creatine kinase
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- N-terminal-pro-brain natriuretic peptide (NT-proBNP)
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Urinalysis-Glucose
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects.
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Urinalysis-Blood
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects. Microscopy will also be assessed if positive for blood): RBC count, WBC count, Casts (Cellular, Granular, Hyaline)
Measured: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Urinalysis-Protein
To assess the safety and tolerability of AZD9977 following oral administration in healthy male subjects. Microscopy will also be assessed if positive for protein): RBC count, WBC count, Casts (Cellular, Granular, Hyaline)
Measured: From screening (Day -28) to follow-up (Week 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2019
- Study start5 Feb 2019
- Primary completion16 Apr 2019
- Study completion16 Apr 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
- Crossover
- Model description
- open-label, randomized, four-way crossover single oral dose
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pablo Forte Soto, MD, MSc, PhD, Principal investigator, Dr.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03804645
- Sponsor's protocol ID
- D6401C00006
- Status last verified
- Apr 2021
- First submitted
- 14 Jan 2019
- Last updated
- 19 Apr 2021
- 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 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, Four-way Crossover Single Oral Dose Study Comparing the Pharmacokinetics of Four Different Formulations of AZD9977 (Part A) and Influence of Food and Lower Dose of a Selected Formulation (Part B) in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT03804645
- Acronym / sponsor ID
- D6401C00006
- Conditions
- Heart Failure
- Keywords
- Mineralocorticoid receptor, Heart failure with preserved ejection fraction, Safety, Pharmacokinetics, Influence of Food, Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 5 Feb 2019 (actual)
- Primary completion
- 16 Apr 2019 (actual)
- Study completion
- 16 Apr 2019 (actual)
- First posted
- 15 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 pharmacokinetics (PK) of four different Formulations of AZD9977 (Part A) and influence of food and lower dose of a selected formulation (Part B) in healthy male subjects.
Detailed description
This study will be a randomized, open-label, single-centre crossover study in healthy male subjects. The study is divided into 2 parts, Part A and Part B. The subjects will participate in both Part A and Part B.
Part A will be a 4-way cross-over study comparing the PK of AZD9977 as a reference capsule and 2 different capsule formulations and a tablet formulation under fasting conditions.
- Treatment A: Reference, AZD9977 capsule
- Treatment B: AZD9977 HDL capsule
- Treatment C: AZD9977 ODL capsule
- Treatment D: AZD9977 tablet In Part B, based on the interim results in Part A, 1 of the formulations will be selected and evaluated at the 300 mg dose level under fed conditions. The same formulation will also be evaluated under fasting conditions at a lower dose level (50 mg). The first dose tested in Part B will be the 50 mg (fasted) dose, followed by the 300 mg (fed) dose.
In Part A, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1) with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 4). Subjects will return to the unit for Part B at least 48 hours (and up to 5 weeks) after completion of Part A.
In Part B, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1) with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 2).
Subjects will return to the unit for a final study visit 5-7 days post-last-dose for a Follow up Visit.
Each subject will be involved in the study for approximately 12 weeks (including approximately 4 to 5 weeks for the interim analysis).
Twelve subjects will initially be randomized to ensure at least 8 and 6 evaluable subjects at the end of the last treatment period for Part A and Part B respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- open-label, randomized, four-way crossover single oral dose
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Treatment A, Drug: Treatment B, Drug: Treatment C, Drug: Treatment DIn Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. |
| Cohort 2 | Experimental | Drug: Treatment A, Drug: Treatment B, Drug: Treatment C, Drug: Treatment DIn Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. |
| Cohort 3 | Experimental | Drug: Treatment A, Drug: Treatment B, Drug: Treatment C, Drug: Treatment DIn Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. |
| Cohort 4 | Experimental | Drug: Treatment A, Drug: Treatment B, Drug: Treatment C, Drug: Treatment DIn Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours. |
| Cohort 5 | Experimental | Drug: Treatment A, Drug: Treatment B, Drug: Treatment C, Drug: Treatment DIn Part B, each subject will receive one formulation from Part A chosen for further development, dose under fed conditions, followed by dose under fasted condition. |
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 subjects aged 18 to 50 years, inclusive, with suitable veins for cannulation or repeated venipuncture at screening.
- 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 at screening.
- Subject judged at screening likely to complete and agree to eat a specified high fat standardized Food and Drug Administration (FDA) breakfast.
Key exclusion criteria (22 listed)
- History of any clinically significant disease or disorder which, in the opinion of the principal investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer'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.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI, including:
- 4.1. Serum potassium > 5.0 mmol/L.
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 |
|---|---|---|
| Treatment AAlso: AZD9977 capsule, referenceEach subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
| Treatment BAlso: AZD9977 HDL capsuleEach subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
| Treatment CAlso: AZD9977 ODL capsuleEach subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
| Treatment DAlso: AZD9977 tabletEach subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
Primary outcome
Area under plasma concentration-time curve from time zero to infinity (AUC)
Time frame: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the influence of food by comparing AUC and Cmax under fasting and fed conditions for 1 of the formulations evaluated in Part A.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
Time frame: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Area under the plasma concentration-time curve from time zero to 24 hours [AUC(0-24)]
Time frame: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Maximum observed plasma concentration (Cmax)
Time frame: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the influence of food by comparing AUC and Cmax under fasting and fed conditions for 1 of the formulations evaluated in Part A.
Observed AZD9977 concentration at 24 hours (C24)
Time frame: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To determine the relative bioavailability (Frel) and compare the plasma concentration time profile of 3 different formulations versus a reference capsule formulation of AZD9977 and to evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Area under plasma concentration-time curve from time zero to infinity divided by dose (AUC/D)
Time frame: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration divided by dose (AUClast/D)
Time frame: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
Area under the plasma concentration-time curve from time zero to 24 hours divided by dose [AUC(0-24)/D]
Time frame: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
Maximum observed plasma concentration divided by dose (Cmax/D)
Time frame: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
Observed AZD9977 concentration at 24 hours divided by dose (C24/D)
Time frame: At Dosing Session, For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment
To evaluate the PK of a lower dose of 1 of the formulations evaluated in Part A
34 secondary outcomes
Number of subjects with Adverse events (AEs)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal blood pressure (BP)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal pulse rate
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal findings in Real-Time Electrocardiogram (Cardiac Telemetry)
Time frame: From Day-1 to follow-up (Week 12)
Number of subjects with abnormal findings in 12-lead safety Electrocardiogram (ECG)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal findings in physical examination
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: absolute count of Basophils, Eosinophils, Monocytes, Neutrophils, Lymphocytes and Reticulocytes; Platelets and White blood cell (WBC) count
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Red blood cell (RBC) count
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Hemoglobin (Hb)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Hematocrit (HCT)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Mean corpuscular volume (MCV)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Mean corpuscular hemoglobin (MCH)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Hematology- Mean corpuscular hemoglobin concentration (MCHC)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry-Sodium
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry-Potassium
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Urea
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Creatinine
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Albumin
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Calcium
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Phosphate
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Glucose (fasting)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- C-reactive protein (CRP)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Alkaline phosphatase (ALP)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Alanine aminotransferase (ALT)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Aspartate aminotransferase (AST)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Gamma glutamyl transpeptidase (GGT)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Total Bilirubin (TBL)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Unconjugated bilirubin
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- High-sensitivity troponin T (hsTnT)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- Creatine kinase
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Serum Clinical Chemistry- N-terminal-pro-brain natriuretic peptide (NT-proBNP)
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Urinalysis-Glucose
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Urinalysis-Blood
Time frame: From screening (Day -28) to follow-up (Week 12)
Number of subjects with abnormal laboratory assessments: Urinalysis-Protein
Time frame: From screening (Day -28) to follow-up (Week 12)
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 19 Apr 2021.
- Study Information posted to AstraZeneca Cinical Trials WebisteLink provided by the sponsor.
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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 Treatment A, Treatment B and Treatment C 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 22 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 19 Apr 2021. 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. 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?
Area under plasma concentration-time curve from time zero to infinity (AUC) (time frame: At Dosing Session, For Part A (Days 1-3, 3-5, 5-7, 7-9) and For Part B (Days 1-2, 3-4): Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post dose of each treatment). The study lists 10 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 19 Apr 2021.