A Single Oral Dose Study to Evaluate Four Different Formulations of AZD9977 and the Effect of Food in Healthy Male Subjects

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: AZD9977 ER capsule (Int. rate); Drug: AZD9977 capsule; Drug: AZD9977 ER capsule (fastvrate); Drug: AZD9977 Oral suspension (reference)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03450759

D6401C00002

Details and patient eligibility

About

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

Full 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.

Enrollment: 13 patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Provision of signed and dated, written informed consent prior to any study specific procedures.
2. Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture.
3. 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.
4. 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.
5. Subject judged likely to complete and agree to eat a specified high-fat, high-calorie standardized FDA breakfast.

Exclusion criteria

1. 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.
2. 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.
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
4. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI including: Serum potassium > 5.0 mmol/L
5. 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)
6. Any clinically significant abnormalities on 12-lead ECG, as judged by the PI.
7. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
8. Known or suspected history of drug abuse in the last 12 months, as judged by the PI.
9. 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.
10. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
11. 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.
12. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.
13. Positive screen for drugs of abuse, cotinine or alcohol at screening or on each admission to the study center.
14. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
15. Use of any prescribed or 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.
16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol in the last 12 months as judged by the PI.
17. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives
18. Subjects who have previously received AZD9977.
19. 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.
20. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
21. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.
22. Subjects with any special dietary restrictions such as subjects that are lactose intolerant or are vegetarians/vegans.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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13 participants in 4 patient groups

Treatment sequence 1

Experimental group

Description:

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:

Drug: AZD9977 ER capsule (Int. rate)

Drug: AZD9977 ER capsule (fastvrate)

Drug: AZD9977 Oral suspension (reference)

Drug: AZD9977 capsule

Treatment sequence 2

Experimental group

Description:

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:

Drug: AZD9977 ER capsule (Int. rate)

Drug: AZD9977 ER capsule (fastvrate)

Drug: AZD9977 Oral suspension (reference)

Drug: AZD9977 capsule

Treatment sequence 3

Experimental group

Description:

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:

Drug: AZD9977 ER capsule (Int. rate)

Drug: AZD9977 ER capsule (fastvrate)

Drug: AZD9977 Oral suspension (reference)

Drug: AZD9977 capsule

Treatment sequence 4

Experimental group

Description:

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)

Treatment:

Drug: AZD9977 ER capsule (Int. rate)

Drug: AZD9977 ER capsule (fastvrate)

Drug: AZD9977 Oral suspension (reference)

Drug: AZD9977 capsule