A Study to Assess the Safety and Tolerability of Single and Multiple Doses of AZD4831 in Healthy Male Subjects

NCT ID: NCT02712372

Last Updated: 2017-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2016-10-31

Brief Summary

This is a Phase I, first-in-human (FIH) study to assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamics (PD) of AZD4831 after single and multiple ascending doses in healthy male subjects

Detailed Description

This is a Phase I, FIH, randomized, single-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamics (PD) of AZD4831 after single (Part 1) and multiple (Part 2) ascending doses in healthy male subjects. The study will be conducted at a single study center with a planned number of subjects of up to 125 healthy males, aged 18 to 50 years.

Conditions

Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Part 1, Dose Level 1

Part 1: Part 1A: Single dose administered in the morning on Day 1 under fasted conditions. Part 1B: Single dose administered in the morning of Day 1 under fed conditions.

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 1, Dose Level 2

Part 1: Part 1A: Single dose administered in the morning on Day 1 under fasted conditions. Part 1B: Single dose administered in the morning of Day 1 under fed conditions.

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 1, Dose Level 3

Part 1: Part 1A: Single dose administered in the morning on Day 1 under fasted conditions. Part 1B: Single dose administered in the morning of Day 1 under fed conditions.

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 1, Dose Level 4

Part 1: Part 1A: Single dose administered in the morning on Day 1 under fasted conditions. Part 1B: Single dose administered in the morning of Day 1 under fed conditions.

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 1, Dose Level 5

Part 1: Part 1A: Single dose administered in the morning on Day 1 under fasted conditions. Part 1B: Single dose administered in the morning of Day 1 under fed conditions.

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 1, Dose Level 6

Part 1: Part 1A: Single dose administered in the morning on Day 1 under fasted conditions. Part 1B: Single dose administered in the morning of Day 1 under fed conditions.

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 2, Dose Level 1

Part 2: Single dose administered in the morning on Day 1 and multiple doses administered once daily, in the morning, Days 3 to 12

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 2, Dose Level 2

Part 2: Single dose administered in the morning on Day 1 and multiple doses administered once daily, in the morning, Days 3 to 12

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

Part 2, Dose Level 3

Part 2: Single dose administered in the morning on Day 1 and multiple doses administered once daily, in the morning, Days 3 to 12

Group Type: EXPERIMENTAL

AZD4831

Intervention Type: DRUG

AZD4831 1-50 mg/g oral suspension

AZD4831 Placebo

Part 1: Part 1A: Single dose administered in the morning on Day 1 under fasted conditions. Part 1B: Single dose administered in the morning of Day 1 under fed conditions.

Part 2: Single dose administered in the morning on Day 1 and multiple doses administered once daily, in the morning, Days 3 to 12

Group Type: PLACEBO_COMPARATOR

AZD4831 placebo

Intervention Type: DRUG

AZD4831 placebo oral suspension

Interventions

AZD4831

AZD4831 1-50 mg/g oral suspension

Intervention Type: DRUG

AZD4831 placebo

AZD4831 placebo oral suspension

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Provision of signed and dated, written informed consent before any study specific procedures.
• Healthy male subjects aged 18 - 50 years, inclusive, with suitable veins for cannulation or repeated venipuncture.
• Have a body mass index (BMI) between 18 and 29.9 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg inclusive.
• Provision of signed, written and dated informed consent for optional genetic/biomarker research.
• Subjects must be able to read, speak and understand the German language.

Exclusion Criteria

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject'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.
• Presence of infection(s) (particularly fungal infection), as judged by the investigator.
• History or current thyroid disease.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), anti-hepatitis B core (anti-HBc) antibodies, hepatitis C antibody and human immunodeficiency virus (HIV).
• Abnormal vital signs
• Any clinically significant abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or LV hypertrophy.
• Prolonged QTcF > 450 ms or shortened QTcF < 340 ms or family history of long QT syndrome.
• PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation)
• PR (PQ) interval prolongation (> 200 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation
• Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS > 110 ms. Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of, for example, ventricular hypertrophy or pre-excitation.
• ECG findings suggesting a metabolic or other non-cardiac condition that may confound interpretation of serial changes (such as hypokalemia).
• Known or suspected history of drug abuse, as judged by the investigator.
• Current smokers or those who have smoked or used nicotine products within the previous 3 months.
• History of alcohol abuse or excessive intake of alcohol, as judged by the investigator.
• Positive screen for drugs of abuse, cotinine (nicotine) or alcohol at screening or admission to the unit before the first administration of IMP.
• History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831.
• Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the investigator.
• Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks before 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 before the first administration of IMP or longer if the medication has a long half-life.
• Plasma donation within 1 month of screening or any blood donation/blood loss > 500 mL during the 3 months before screening.
• 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.
• Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
• Involvement of any Astra Zeneca, PAREXEL or study site employee or their close relatives.
• Judgment by the investigator 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.
• Subjects who are vegans or have medical dietary restrictions.
• Subjects who cannot communicate reliably with the investigator.

Exclusion from the genetic research:

• Previous bone marrow transplant.
• Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainard Fuhr, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

PAREXEL Early Phase Clinical Unit Berlin, On the premises of Klinikum Westend, Haus 31, Spandauer Damm 130, 14050 Berlin, Germany

Other Identifiers

D6580C00001

Identifier Type: -

Identifier Source: org_study_id