A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD6615 in Healthy Subjects

NCT04055168 | Terminated Phase 1 FDA Drug

• 1 other identifier: D7991C00001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This study will be a randomized, single-blind, placebo-controlled, single-ascending dose (SAD), sequential group study. It is a SAD study in healthy Non-Asian subjects (Part 1) and healthy Japanese subjects (Part 2) to assess the safety and tolerability of AZD6615 and to characterize the pharmacokinetics (PK) of AZD6615.

Conditions

Dyslipidemia

Keywords

Dyslipidemia; Single Ascending Dose; Safety; Tolerability

Outcome Measures

Primary Outcomes (1)

• Number of subjects with adverse events (AEs) and serious adverse events (SAEs)

  To assess the safety and tolerability of AZD6615 following the administration of SAD

  From screening to 12 weeks of follow-up

Secondary Outcomes (15)

• Plasma PK analysis: Maximum observed concentration (Cmax)

  Days 1 to 4: Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose

• Plasma PK analysis: Time to reach maximum observed concentration (tmax)

  Days 1 to 4: Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose

• Plasma PK analysis: Terminal half-life (t½λz)

  Days 1 to 4: Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose

• Plama PK analysis: Terminal elimination rate constant (λz)

  Days 1 to 4: Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose

• Plasma PK analysis: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast)

  Days 1 to 4: Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose

Study Arms (5)

Cohort 1 - Part 1

EXPERIMENTAL

On Day 1, randomized subjects (healthy non-Asian subjects) will receive dose 1 of AZD6615 (6 subjects) or matching placebo (2 subjects).

Drug: AZD6615; Drug: Placebo

Cohort 2 - Part 1

EXPERIMENTAL

On Day 1, randomized subjects (healthy non-Asian subjects) will receive dose 2 of AZD6615 (6 subjects) or matching placebo (2 subjects).

Drug: AZD6615; Drug: Placebo

Cohort 3 - Part 1

EXPERIMENTAL

On Day 1, randomized subjects (healthy non-Asian subjects) will receive dose 3 of AZD6615 (6 subjects) or matching placebo (2 subjects).

Drug: AZD6615; Drug: Placebo

Cohort 1 - Part 2

EXPERIMENTAL

On Day 1, randomized subjects (healthy Japanese subjects) will receive dose 1 of AZD6615 (6 subjects) or matching placebo (2 subjects).

Drug: AZD6615; Drug: Placebo

Cohort 2 - Part 2

EXPERIMENTAL

On Day 1, randomized subjects (healthy Japanese subjects) will receive dose 2 of AZD6615 (6 subjects) or matching placebo (2 subjects).

Drug: AZD6615; Drug: Placebo

Interventions

AZD6615 DRUG

AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.

Also known as: Study drug

Cohort 1 - Part 1; Cohort 1 - Part 2; Cohort 2 - Part 1; Cohort 2 - Part 2; Cohort 3 - Part 1

Placebo DRUG

Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.

Also known as: Control

Cohort 1 - Part 1; Cohort 1 - Part 2; Cohort 2 - Part 1; Cohort 2 - Part 2; Cohort 3 - Part 1

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of non-child-bearing potential.
• Provision of signed, written and dated informed consent for optional genetic research.
• : In Part 1: Healthy male and/or female Non-Asian subjects aged 20 - 60 years (inclusive at Screening Visit) with suitable veins for cannulation or repeated venipuncture. In Part 2: Healthy male and/or female Japanese subjects aged 20 - 60 years (inclusive at Screening Visit) with suitable veins for cannulation or repeated venipuncture.
• \. Have a body mass index between 18 and 30 kg/m\^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive at the Screening Visit and Day -1.
• \. Males should avoid fathering a child by either true abstinence or a highly effective contraception form of birth control during the study.

You may not qualify if:

• History of any clinically important 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, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
• Subjects with known autoimmune disease or on treatment with immune-modulatory drugs.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the administration of investigational medicinal product.
• Any laboratory values with the following deviations at the Screening Visit and/or Day -1, test may be repeated once for each visit at the discretion of the Investigator if out of range: (Alanine aminotransferase \> upper limit of normal \[ULN\], Aspartate aminotransferase \> ULN, Creatinine \> ULN, White blood cell count \< 3.5 x 10\^9/L, Hb \< lower limit of normal \[LLN\], Platelet count \<LLN).
• Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.
• Abnormal vital signs, any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-Lead ECG as considered by the Investigator, that may interfere with the interpretation of QTc interval changes.
• Known or suspected history of drug abuse, current smoker or those who have smoked or used nicotine products within the previous 3 months before the Screening Visit.
• History of alcohol abuse and/or severe allergy/hypersensitivity.
• Previous bone marrow transplant.
• Males who are unwilling to use an acceptable method of birth control during the entire study period.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (2)

Research Site

Glendale, California, 91206, United States

Location

Research Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• Makhmudova U, Steinhagen-Thiessen E, Volpe M, Landmesser U. Advances in nucleic acid-targeted therapies for cardiovascular disease prevention. Cardiovasc Res. 2024 Sep 2;120(10):1107-1125. doi: 10.1093/cvr/cvae136.

  PMID: 38970537 DERIVED

MeSH Terms

Conditions

Dyslipidemias

Interventions

Drug Evaluation

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• David Han, MD

  California Clinical Trials Medical Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 15, 2019
• First Posted: August 13, 2019
• Study Start: July 24, 2019
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: December 14, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (2)