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

December 11, 2020 updated by: AstraZeneca

A Phase I Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD6615 After Single Dosing to Healthy Subjects

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study part is planned to consist of 3 cohorts of Non-Asian subjects (Part 1) and 2 cohorts of Japanese subjects (Part 2). Part 2 will be initiated no earlier than after completion of the last Safety Review Committee (SRC) review in Part 1. Healthy male and/or female subjects aged 20 to 60 years will be included in both Parts 1 and 2 of the study. Female subjects must be of non-childbearing potential. Study Part 1 is planned to be conducted in 24 subjects but may be conducted in up to 40 subjects. Study Part 2 is planned to be conducted in 16 subjects but may be conducted in up to 32 subjects.

Within each cohort of Parts 1 and 2, 6 subjects will be randomized to receive AZD6615 and 2 subjects will be randomized to receive placebo. Dosing and food intake should be supervised and documented by study staff when subjects are in the clinic.

The study will comprise of:

  • A Screening Period of maximum 28 days.
  • A Dosing Session during which subjects will be resident at the Clinical Unit from the day before IMP administration (Day -1) until at least 78 hours after Investigational medicinal product (IMP) administration; discharged on Day 4.
  • A Follow-Up Period of 12 weeks that will consist of 6 Follow-Up Visits, for which the subjects will return to the Clinical Unit at 2, 4, 6, 8, 10, and 12 weeks post-dose.

Within each cohort, site personnel remain blinded until the SRC meeting.

Following review of the data, the SRC may also decide to adjust the following for subsequent cohorts:

  • The time window between the sentinel dose group and the main dose group in Part 1.
  • The length of the stay at the study site, the timing and number of assessments and/or samples.
  • The length of the follow-up period.
  • The length of the data collection period for the SRC review.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Glendale, California, United States, 91206
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21225
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provision of signed and dated, written informed consent prior to any study specific procedures.
  2. 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.
  3. Provision of signed, written and dated informed consent for optional genetic research.

4: 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.

5. 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.

6. Males should avoid fathering a child by either true abstinence or a highly effective contraception form of birth control during the study.

Exclusion Criteria:

  1. 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.
  2. History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
  3. Subjects with known autoimmune disease or on treatment with immune-modulatory drugs.
  4. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the administration of investigational medicinal product.
  5. 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).
  6. Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.
  7. 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.
  8. 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.
  9. History of alcohol abuse and/or severe allergy/hypersensitivity.
  10. Previous bone marrow transplant.
  11. Males who are unwilling to use an acceptable method of birth control during the entire study period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 - Part 1
On Day 1, randomized subjects (healthy non-Asian subjects) will receive dose 1 of AZD6615 (6 subjects) or matching placebo (2 subjects).
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Study drug
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Control
Experimental: Cohort 2 - Part 1
On Day 1, randomized subjects (healthy non-Asian subjects) will receive dose 2 of AZD6615 (6 subjects) or matching placebo (2 subjects).
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Study drug
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Control
Experimental: Cohort 3 - Part 1
On Day 1, randomized subjects (healthy non-Asian subjects) will receive dose 3 of AZD6615 (6 subjects) or matching placebo (2 subjects).
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Study drug
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Control
Experimental: Cohort 1 - Part 2
On Day 1, randomized subjects (healthy Japanese subjects) will receive dose 1 of AZD6615 (6 subjects) or matching placebo (2 subjects).
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Study drug
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Control
Experimental: Cohort 2 - Part 2
On Day 1, randomized subjects (healthy Japanese subjects) will receive dose 2 of AZD6615 (6 subjects) or matching placebo (2 subjects).
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Study drug
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Names:
  • Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Time Frame: From screening to 12 weeks of follow-up
To assess the safety and tolerability of AZD6615 following the administration of SAD
From screening to 12 weeks of follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma PK analysis: Maximum observed concentration (Cmax)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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-time curve from time zero to 24 hours after dosing (AUC0-24)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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 concentration-time curve from time zero extrapolated to infinity (AUC)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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: Apparent volume of distribution (Vz/F)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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: Apparent total body clearance (CL/F)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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-time curve from time zero extrapolated to infinity divided by the dose administered (AUC/D)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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-time curve from time zero to 24 hours after dosing divided by the dose administered (AUC0-24/D)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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-time curve from time zero to time of last quantifiable analyte concentration divided by the dose administered (AUClast/D)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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: Mean Residence Time from time 0 to infinity (MRT)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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: Observed maximum concentration divided by the dose administered (Cmax/D)
Time Frame: 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
To characterize the PK of AZD6615 after single dosing
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
PD analysis: Levels of dyslipidemia related biomarkers
Time Frame: At screening, on Days -1, Days 1 to 4 (Pre-dose and at 24, 48 and 72 hours post-dose), Weeks 2 to 10 (at 2, 4, 6 and 8 weeks post-dose) and on Week 12 post-dose
This study will also investigate the PD of AZD6615 by investigating the effect of AZD6615 on levels of dyslipidemia related biomarkers
At screening, on Days -1, Days 1 to 4 (Pre-dose and at 24, 48 and 72 hours post-dose), Weeks 2 to 10 (at 2, 4, 6 and 8 weeks post-dose) and on Week 12 post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: David Han, MD, California Clinical Trials Medical Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 24, 2019

Primary Completion (Actual)

February 10, 2020

Study Completion (Actual)

February 10, 2020

Study Registration Dates

First Submitted

July 15, 2019

First Submitted That Met QC Criteria

August 12, 2019

First Posted (Actual)

August 13, 2019

Study Record Updates

Last Update Posted (Actual)

December 14, 2020

Last Update Submitted That Met QC Criteria

December 11, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • D7991C00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing 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

IPD Sharing 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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