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

NCT02712372 | Terminated Phase 1

• 1 other identifier: D6580C00001
• Study Type: interventional
• Target: 104
• Locations: 0 countries
• Sites: N/A

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

Conditions

Cardiovascular Disease

Keywords

AZD4831 oral suspension; Healthy male subjects; Safety; Tolerability; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (13)

• Frequencies of adverse events

  To assess the safety and tolerability of single and multiple doses of AZD4831

  From screening up to 10 days post final dose

• Supine blood pressure (Part 1)

  To assess change from baseline in supine blood pressure

  From screening up to 48 hours post dose

• Supine pulse rate (Part 1)

  To assess change from baseline in supine pulse rate

  From screening up to 48 hours post dose

• Supine body temperature (Part 2)

  To assess change from baseline in supine body temperature

  From screening up to pre-dose Day 12

• 12-lead electrocardiogram

  To assess 12-lead electrocardiogram

  From screening up to 10 days post final dose

• 12-lead electrocardiogram (cardiac telemetry)

  12-lead electrocardiogram (cardiac telemetry)

  From Day-1 up to 24 hours post final dose

• Physical examination

  To assess subject through a physical examination, including assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.

  From screening up to 10 days post final dose

• To assess the subject through hematology laboratory assessment

  To assess a subject through hematology laboratory assessment

  From screening up to 10 days post final dose

• Percentage of adverse events

  To assess the safety and tolerability of single and multiple doses of AZD4831

  From screening to 10 days post final dose

• Supine blood pressure (Part 2)

  To assess change from baseline in supine blood pressure

  From screening up to 10 days post final dose

• Supine pulse rate (Part 2)

  To assess change from baseline in supine pulse rate

  From screening up to 10 days post final dose

• Chemistry evaluations

  including high-sensitivity C-reactive protein {hs-CRP} and thyroid panel

  From screening up to 10 days post final dose

• To assess the subject through urinalysis laboratory assessment

  To assess a subject through urinalysis laboratory assessment

  From screening up to 10 days post final dose

Secondary Outcomes (22)

• Observed maximum plasma concentration, taken directly from the individual concentration-time curve (Cmax)

  From pre-dose up to 48 hours post dose

• Time to reach maximum plasma concentration, taken directly from the individual concentration-time curve (tmax)

  From pre-dose up to 48 hours post dose

• Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz)

  From pre-dose up to 48 hours post dose

• Terminal half-life, estimated as (ln2)/λz (t1/2λz)

  From pre-dose up to 48 hours post dose

• Area under the plasma concentration-curve over 24 hours (AUCτ)

  From pre-dose up to 48 hours post dose

Study Arms (10)

Part 1, Dose Level 1

EXPERIMENTAL

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.

Drug: AZD4831

Part 1, Dose Level 2

EXPERIMENTAL

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.

Drug: AZD4831

Part 1, Dose Level 3

EXPERIMENTAL

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.

Drug: AZD4831

Part 1, Dose Level 4

EXPERIMENTAL

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.

Drug: AZD4831

Part 1, Dose Level 5

EXPERIMENTAL

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.

Drug: AZD4831

Part 1, Dose Level 6

EXPERIMENTAL

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.

Drug: AZD4831

Part 2, Dose Level 1

EXPERIMENTAL

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

Drug: AZD4831

Part 2, Dose Level 2

EXPERIMENTAL

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

Drug: AZD4831

Part 2, Dose Level 3

EXPERIMENTAL

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

Drug: AZD4831

AZD4831 Placebo

PLACEBO COMPARATOR

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

Drug: AZD4831 placebo

Interventions

AZD4831 DRUG

AZD4831 1-50 mg/g oral suspension

Part 1, Dose Level 1; Part 1, Dose Level 2; Part 1, Dose Level 3; Part 1, Dose Level 4; Part 1, Dose Level 5; Part 1, Dose Level 6; Part 2, Dose Level 1; Part 2, Dose Level 2; Part 2, Dose Level 3

AZD4831 placebo DRUG

AZD4831 placebo oral suspension

AZD4831 Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

AZD4831

Study Officials

• Rainard Fuhr, Dr. med.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: March 18, 2016
• Study Start: June 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: January 6, 2017

Record last verified: 2017-01