Healthy VolunteersPhase 1NCT03450759
A Single Oral Dose Study to Evaluate Four Different Formulations of AZD9977 and the Effect of Food in Healthy Male Subjects
A Phase 1 study testing AZD9977 Oral suspension (reference), AZD9977 capsule and AZD9977 ER capsule (fastvrate) in people with Healthy Volunteers, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
This study will evaluate pharmacokinetics (PK) of four different formulations with different release profiles of AZD9977 (PART A) in the fasted state, and one of the formulation will be selected for further development (Part B). In Part B, the influence of food on the PK of AZD9977 will be evaluated 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
- Healthy Volunteers
- What is being tested?
- AZD9977 Oral suspension (reference), AZD9977 capsule and AZD9977 ER capsule (fastvrate)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Mar 2018to 6 Jun 2018
- 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.
- Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture.
- 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 research. If a subject decline to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
- Subject judged likely to complete and agree to eat a specified high-fat, high-calorie standardized FDA breakfast.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the 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 (GI), 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: Serum potassium > 5.0 mmol/L
- Any clinically significant abnormal findings in vital signs as specified below and as judged by the PI at screening and on admission: Systolic blood pressure (SBP) < 90 mmHg or > 140 mmHg; Diastolic blood pressure (DBP) < 50 mmHg or > 90 mmHg; Heart rate (HR) < 45 or > 90 beats per minute (bpm)
- Any clinically significant abnormalities on 12-lead ECG, as judged by the PI.
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- 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 last 12 months, 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 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. 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, cotinine or alcohol at screening or on each 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 IMP.
- 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 IMP 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 last 12 months 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.
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.
- Subjects with any special dietary restrictions such as subjects that are lactose intolerant or are vegetarians/vegans.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomized, Four-way Cross-over, Single Oral Dose Study Comparing the Pharmacokinetics of Four Different Formulations of AZD9977 (Part A) and Influence of Food (Part B) in Healthy Male Subjects
This study will evaluate pharmacokinetics (PK) of four different formulations with different release profiles of AZD9977 (PART A) in the fasted state, and one of the formulation will be selected for further development (Part B). In Part B, the influence of food on the PK of AZD9977 will be evaluated
Read the detailed description
This study is a randomized, open-label, single-center study conducted on 12 healthy male subjects. This consists of three periods:
- Screening period (only prior to Day-1)
- Residential/treatment period (Part A and Part B)
- Follow-up period (5 to 7 days after-final dose)
The study is divided into 2 parts: Part A and B. The subjects will participate in both Part A and Part B. Part A will be a 4-way cross-over study to compare the PK of 3 different solid formulations with different release rates with an oral suspension of AZD9977 in fasting conditions. Subjects in Part A will receive the following treatments on Days 1, 3, 5 and 7:
- AZD9977 oral suspension 15 mg/mL (15 mg/mL = 195 mg) (reference)
- AZD9977 capsule, 65 mg (3 x 65 mg = 195 mg)
- AZD9977 extended release (ER) capsule, 65 mg, fast (3 x 65 mg = 195 mg)
- AZD9977 ER capsule, 65 mg, intermediate release (Int) (3 x 65 mg = 195 mg) Subjects will be resident from 1 day before Part A until at least 36 hours post last dosing in Part A. Subjects will return to the unit for Part B after completion of Part A. There will be a washout period of at least 2 days between the doses for a subject. Based on the results in Part A, one of the solid formulations will be selected and evaluated in fed conditions on Day of Part B. Subjects will return to the unit for a final study visit 5 to 7 days post- dose in Part B. Each subject will be involved in the study for approximately 9 weeks.
- Conditions
- Healthy Volunteers
- Being tested
- AZD9977 Oral suspension (reference), AZD9977 capsule, AZD9977 ER capsule (fastvrate), AZD9977 ER capsule (Int. rate)
- Keywords
- Heart failure., Mineralocorticoid receptor modulator., Heart failure with preserved ejection fraction (HFpEF).
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9977 Oral suspension (reference)Drug
Randomized subjects will receive single oral dose of AZD9977 oral suspension 15 mg/mL on Days 1, 3, 5 and 7 in Part A.
AZD9977 capsuleDrug
Randomized subjects will receive single oral dose of AZD9977 capsule 65 mg on Days 1, 3, 5 and 7 in Part A.
AZD9977 ER capsule (fastvrate)Drug
Randomized subjects will receive single oral dose of AZD9977 ER capsule (fast rate) 65 mg on Days 1, 3, 5 and 7 in Part A.
AZD9977 ER capsule (Int. rate)Drug
Randomized subjects will receive single oral dose of AZD9977 ER capsule (Int rate) 65 mg on Days 1, 3, 5 and 7 in Part A.
| Study group | Role | What they receive |
|---|---|---|
| Treatment sequence 1 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence:
AZD9977 oral suspension (reference) AZD9977 capsule AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) Receives: Drug: AZD9977 Oral suspension (reference); Drug: AZD9977 capsule; Drug: AZD9977 ER capsule (fastvrate); Drug: AZD9977 ER capsule (Int. rate) |
| Treatment sequence 2 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence:
AZD9977 capsule AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) AZD9977 oral suspension (reference) Receives: Drug: AZD9977 Oral suspension (reference); Drug: AZD9977 capsule; Drug: AZD9977 ER capsule (fastvrate); Drug: AZD9977 ER capsule (Int. rate) |
| Treatment sequence 3 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence:
AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) AZD9977 Oral suspension (reference) AZD9977 capsule Receives: Drug: AZD9977 Oral suspension (reference); Drug: AZD9977 capsule; Drug: AZD9977 ER capsule (fastvrate); Drug: AZD9977 ER capsule (Int. rate) |
| Treatment sequence 4 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence:
AZD9977 ER capsule (Int. rate) AZD9977 Oral suspension (reference) AZD9977 capsule AZD9977 ER capsule (fast rate) Receives: Drug: AZD9977 Oral suspension (reference); Drug: AZD9977 capsule; Drug: AZD9977 ER capsule (fastvrate); Drug: AZD9977 ER capsule (Int. rate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under plasma concentration-time curve from time zero to infinity (AUC)
To assess Frel by assessments of PK parameters AUC after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast)
To assess Frel by assessments of PK parameters AUClast after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under the plasma concentration-time curve from time zero to time 24 hours (AUC[0-24])
To assess Frel by assessments of PK parameters AUC[0-24] after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Maximum observed plasma concentration (Cmax )
To assess Frel by assessments of PK parameters Cmax after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Area under plasma concentration-time curve from time zero to infinity (AUC)
To assess AUC after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
To assess AUClast after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Maximum observed plasma concentration (Cmax)
To assess Cmax after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Area under the plasma concentration-time curve from time zero to time 24 hours (AUC[0-24])
To assess AUC(0-24) after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7
The Effect of food on the PK of one of the solid formultaion evaluated in Part A under fasting and fed conditions in Part B
To evaluate the influence of food by comparing AUC and Cmax under fasting and fed conditions for one of the solid formulations evaluated in Part A.
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Secondary outcomes (34)
Plasma PK parameter: Plasma concentration 24 hours post-dose (C4)
To assess C24 after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A and Part B - Day 1 (24 hours post-dose)
Plasma PK parameter: Time to reach maximum observed plasma concentration (tmax)
To assess tmax after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz )
To assess t½λz after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)
To assess MRT after administration of single oral dose of AZD9977 capsule, ER (fast rate and Int. rate) capsules and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Terminal elimination rate constant (λz)
To assess λz after administration of single oral dose of AZD9977 capsule, ER (fast rate and Int. rate) capsules and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Apparent total body clearance of drug from plasma after extravascular administration AZD9977 (CL/F)
To assess CL/F after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Apparent volume of distribution during the terminal phase after extravascular administration AZD9977 (Vz/F)
To assess Vz/F after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Number of subjects with adverse events (AEs) due to AZD9977
To assess AEs as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). AEs will be collected from the start of screening throughout the treatment period up to and including the follow-up visit. Serious AEs will be recorded from the time of informed consent.
Measured: From screening up to follow-up (5 to 7 days after final dose)
Vital sign: Blood pressure [BP]
To assess supine position systolic and diastolic BP as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). Both SBP and DBP will be collected after the subject has rested in the supine position for at least 5 minutes.
Measured: From screening up to follow-up (5 to 7 days after final dose)
Vital sign: Pulse rate
To assess supine position pulse rate as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). Pulse rate will be collected after the subject has rested in the supine position for at least 5 minutes.
Measured: From screening up to follow-up (5 to 7 days after final dose)
Number of participants with abnormal findings in Resting 12-lead Electrocardiogram (ECG)
To assess any clinically significant abnormalities in the cardiovascular system functioning using a 10-second 12-lead ECG as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). The specific type and nature of the abnormality will be documented in ClinBase. Clinically significant findings will also be documented on the AE page of the CRF if applicable.
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Number of participants with abnormal physical examination findings
To assess any clinically significant abnormal physical examination findings as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). Brief physical examination includes assessment of the general appearance, skin, abdomen, cardiovascular system and respiratory. Full physical examination includes assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Blood cells count
To assess red blood cells ( RBC) and white blood cells (WBC) countas a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Hemoglobin (Hb)
To assess Hb as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Hematocrit (HCT) and Reticulocyte absolute count
To assess HCT (RBC) and reticulocyte absolute count (immature RBCs) as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Mean corpuscular volume (MCV)
To assess MCV as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
To assess MCH as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
To assess MCHC as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Differential count
To assess differential WBC count (absolute count of neutrophils, lymphocytes, monocyets, eosinophils and basophils) as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Platelets
To assess platelets count as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - sodium, potassium, calcium and phosphate
To assess serum sodium, potassium, calcium and phosphate level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Urea and Uric acid
To assess serum urea and uric acid level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Creatinine
To assess serum creatinine level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Albumin
To assess serum albumin level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Glucose (fasting)
To assess serum fasting glucose level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - C-reactive protein (CRP)
To assess serum CRP level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Liver enzymes
To assess serum Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Bilirubin
To assess serum bilirubin (total and unconjugated) level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - High-sensitivity troponin T
To assess serum high-sensitivity troponin T level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Creatine kinase
To assess serum creatine kinase level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - N-terminal-pro-brain natriuretic peptide (NT-proBNP)
To assess serum NT-proBNP level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Clinical Urinalysis - Glucose
To assess urine glucose level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Clinical Urinalysis - Protein
To assess urine protein level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). If urinalysis is positive for protein, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Clinical Urinalysis - Blood
To assess presence of blood in urine as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]).
Measured: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2018
- Study start28 Mar 2018
- Primary completion6 Jun 2018
- Study completion6 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies 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
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03450759
- Sponsor's protocol ID
- D6401C00002
- Status last verified
- Jun 2018
- First submitted
- 15 Feb 2018
- Last updated
- 15 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, Four-way Cross-over, Single Oral Dose Study Comparing the Pharmacokinetics of Four Different Formulations of AZD9977 (Part A) and Influence of Food (Part B) in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT03450759
- Acronym / sponsor ID
- D6401C00002
- Conditions
- Healthy Volunteers
- Keywords
- Heart failure., Mineralocorticoid receptor modulator., Heart failure with preserved ejection fraction (HFpEF).
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 28 Mar 2018 (actual)
- Primary completion
- 6 Jun 2018 (actual)
- Study completion
- 6 Jun 2018 (actual)
- First posted
- 1 Mar 2018 (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.
This study will evaluate pharmacokinetics (PK) of four different formulations with different release profiles of AZD9977 (PART A) in the fasted state, and one of the formulation will be selected for further development (Part B). In Part B, the influence of food on the PK of AZD9977 will be evaluated
Detailed description
This study is a randomized, open-label, single-center study conducted on 12 healthy male subjects. This consists of three periods:
- Screening period (only prior to Day-1)
- Residential/treatment period (Part A and Part B)
- Follow-up period (5 to 7 days after-final dose)
The study is divided into 2 parts: Part A and B. The subjects will participate in both Part A and Part B. Part A will be a 4-way cross-over study to compare the PK of 3 different solid formulations with different release rates with an oral suspension of AZD9977 in fasting conditions. Subjects in Part A will receive the following treatments on Days 1, 3, 5 and 7:
- AZD9977 oral suspension 15 mg/mL (15 mg/mL = 195 mg) (reference)
- AZD9977 capsule, 65 mg (3 x 65 mg = 195 mg)
- AZD9977 extended release (ER) capsule, 65 mg, fast (3 x 65 mg = 195 mg)
- AZD9977 ER capsule, 65 mg, intermediate release (Int) (3 x 65 mg = 195 mg) Subjects will be resident from 1 day before Part A until at least 36 hours post last dosing in Part A. Subjects will return to the unit for Part B after completion of Part A. There will be a washout period of at least 2 days between the doses for a subject. Based on the results in Part A, one of the solid formulations will be selected and evaluated in fed conditions on Day of Part B. Subjects will return to the unit for a final study visit 5 to 7 days post- dose in Part B. Each subject will be involved in the study for approximately 9 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment sequence 1 | Experimental | Drug: AZD9977 Oral suspension (reference), Drug: AZD9977 capsule, Drug: AZD9977 ER capsule (fastvrate), Drug: AZD9977 ER capsule (Int. rate)In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 oral suspension (reference) AZD9977 capsule AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) |
| Treatment sequence 2 | Experimental | Drug: AZD9977 Oral suspension (reference), Drug: AZD9977 capsule, Drug: AZD9977 ER capsule (fastvrate), Drug: AZD9977 ER capsule (Int. rate)In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 capsule AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) AZD9977 oral suspension (reference) |
| Treatment sequence 3 | Experimental | Drug: AZD9977 Oral suspension (reference), Drug: AZD9977 capsule, Drug: AZD9977 ER capsule (fastvrate), Drug: AZD9977 ER capsule (Int. rate)In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) AZD9977 Oral suspension (reference) AZD9977 capsule |
| Treatment sequence 4 | Experimental | Drug: AZD9977 Oral suspension (reference), Drug: AZD9977 capsule, Drug: AZD9977 ER capsule (fastvrate), Drug: AZD9977 ER capsule (Int. rate)In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 ER capsule (Int. rate) AZD9977 Oral suspension (reference) AZD9977 capsule AZD9977 ER capsule (fast rate) |
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.
- Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture.
- 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 research. If a subject decline to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
- Subject judged likely to complete and agree to eat a specified high-fat, high-calorie standardized FDA breakfast.
Key exclusion criteria (22 listed)
- History of any clinically significant disease or disorder which, in the opinion of the 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 (GI), 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: Serum potassium > 5.0 mmol/L
- Any clinically significant abnormal findings in vital signs as specified below and as judged by the PI at screening and on admission: Systolic blood pressure (SBP) < 90 mmHg or > 140 mmHg; Diastolic blood pressure (DBP) < 50 mmHg or > 90 mmHg; Heart rate (HR) < 45 or > 90 beats per minute (bpm)
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 |
|---|---|---|
| AZD9977 Oral suspension (reference)Randomized subjects will receive single oral dose of AZD9977 oral suspension 15 mg/mL on Days 1, 3, 5 and 7 in Part A. | Drug | Treatment sequence 1, Treatment sequence 2, Treatment sequence 3, Treatment sequence 4 |
| AZD9977 capsuleRandomized subjects will receive single oral dose of AZD9977 capsule 65 mg on Days 1, 3, 5 and 7 in Part A. | Drug | Treatment sequence 1, Treatment sequence 2, Treatment sequence 3, Treatment sequence 4 |
| AZD9977 ER capsule (fastvrate)Randomized subjects will receive single oral dose of AZD9977 ER capsule (fast rate) 65 mg on Days 1, 3, 5 and 7 in Part A. | Drug | Treatment sequence 1, Treatment sequence 2, Treatment sequence 3, Treatment sequence 4 |
| AZD9977 ER capsule (Int. rate)Randomized subjects will receive single oral dose of AZD9977 ER capsule (Int rate) 65 mg on Days 1, 3, 5 and 7 in Part A. | Drug | Treatment sequence 1, Treatment sequence 2, Treatment sequence 3, Treatment sequence 4 |
Primary outcome
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under plasma concentration-time curve from time zero to infinity (AUC)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To assess Frel by assessments of PK parameters AUC after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To assess Frel by assessments of PK parameters AUClast after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under the plasma concentration-time curve from time zero to time 24 hours (AUC[0-24])
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To assess Frel by assessments of PK parameters AUC[0-24] after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Maximum observed plasma concentration (Cmax )
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To assess Frel by assessments of PK parameters Cmax after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference).
Plasma PK parameter: Area under plasma concentration-time curve from time zero to infinity (AUC)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To assess AUC after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Plasma PK parameter: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To assess AUClast after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Plasma PK parameter: Maximum observed plasma concentration (Cmax)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To assess Cmax after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
Plasma PK parameter: Area under the plasma concentration-time curve from time zero to time 24 hours (AUC[0-24])
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7
To assess AUC(0-24) after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference).
The Effect of food on the PK of one of the solid formultaion evaluated in Part A under fasting and fed conditions in Part B
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
To evaluate the influence of food by comparing AUC and Cmax under fasting and fed conditions for one of the solid formulations evaluated in Part A.
34 secondary outcomes
Plasma PK parameter: Plasma concentration 24 hours post-dose (C4)
Time frame: Dosing sessions: Part A and Part B - Day 1 (24 hours post-dose)
Plasma PK parameter: Time to reach maximum observed plasma concentration (tmax)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz )
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Terminal elimination rate constant (λz)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Apparent total body clearance of drug from plasma after extravascular administration AZD9977 (CL/F)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Plasma PK parameter: Apparent volume of distribution during the terminal phase after extravascular administration AZD9977 (Vz/F)
Time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1
Number of subjects with adverse events (AEs) due to AZD9977
Time frame: From screening up to follow-up (5 to 7 days after final dose)
Vital sign: Blood pressure [BP]
Time frame: From screening up to follow-up (5 to 7 days after final dose)
Vital sign: Pulse rate
Time frame: From screening up to follow-up (5 to 7 days after final dose)
Number of participants with abnormal findings in Resting 12-lead Electrocardiogram (ECG)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Number of participants with abnormal physical examination findings
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Blood cells count
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Hemoglobin (Hb)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Hematocrit (HCT) and Reticulocyte absolute count
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Mean corpuscular volume (MCV)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Differential count
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Hematology - Platelets
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - sodium, potassium, calcium and phosphate
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Urea and Uric acid
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Creatinine
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Albumin
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Glucose (fasting)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - C-reactive protein (CRP)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Liver enzymes
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Bilirubin
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - High-sensitivity troponin T
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - Creatine kinase
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Serum Clinical chemistry - N-terminal-pro-brain natriuretic peptide (NT-proBNP)
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Clinical Urinalysis - Glucose
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Clinical Urinalysis - Protein
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose)
Laboratory assessments: Clinical Urinalysis - Blood
Time frame: At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final 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 15 Jun 2018.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Oral suspension (reference), AZD9977 capsule and AZD9977 ER capsule (fastvrate) in people with Healthy Volunteers, 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 15 Jun 2018. 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?
Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under plasma concentration-time curve from time zero to infinity (AUC) (time frame: Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1). The study lists 9 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 15 Jun 2018.