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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04055168
Recruitment Status : Terminated (It was decided to not run the Japanese cohorts in the study.)
First Posted : August 13, 2019
Last Update Posted : December 14, 2020
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Dyslipidemia Drug: AZD6615 Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Phase I Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD6615 After Single Dosing to Healthy Subjects
Actual Study Start Date : July 24, 2019
Actual Primary Completion Date : February 10, 2020
Actual Study Completion Date : February 10, 2020

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).
Drug: AZD6615
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: Study drug

Drug: Placebo
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: 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).
Drug: AZD6615
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: Study drug

Drug: Placebo
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: 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).
Drug: AZD6615
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: Study drug

Drug: Placebo
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: 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).
Drug: AZD6615
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: Study drug

Drug: Placebo
Placebo (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: 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).
Drug: AZD6615
AZD6615 (dose 1, dose 2, or dose 3) will be administered as a single dose to the randomized subjects.
Other Name: Study drug

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04055168


Locations
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United States, California
Research Site
Glendale, California, United States, 91206
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
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Principal Investigator: David Han, MD California Clinical Trials Medical Group
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04055168    
Other Study ID Numbers: D7991C00001
First Posted: August 13, 2019    Key Record Dates
Last Update Posted: December 14, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Dyslipidemia
Single Ascending Dose
Safety
Tolerability
Additional relevant MeSH terms:
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Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases