A Study to Assess the Drug Absorption Into the Blood After Administration of 3 Doses of AZD5718

NCT04087187 | Completed Phase 1 DMC

• 1 other identifier: D7550C00009
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted to evaluate the AZD5718 pharmacokinetic (PK) doses in order to determine exposure in a new dose range and compare with previous results. This study will include 14 subjects in a single site in United Kingdom. Each subject will be involved in the study for 6 to 7 weeks.

Conditions

Coronary Artery Disease

Keywords

Pharmacokinetics

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetic parameter: Area under plasma concentration time curve from zero to infinity (AUC)

  To evaluate the pharmacokinetics and exposure of 3 different doses of AZD5718

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

• Pharmacokinetic parameter: Area under the plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)

  To evaluate the pharmacokinetics and exposure of 3 different doses of AZD5718

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

• Pharmacokinetic parameter: Maximum observed plasma concentration (Cmax)

  To evaluate the pharmacokinetics and exposure of 3 different doses of AZD5718

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

• Pharmacokinetic parameter: Drug concentration 24 hours after dosing (C24)

  To evaluate the pharmacokinetics and exposure of 3 different doses of AZD5718

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

• Pharmacokinetic parameter: Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t1/2λz)

  To evaluate the pharmacokinetics and exposure of 3 different doses of AZD5718

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

• Pharmacokinetic parameter: Time to reach maximum observed plasma concentration (tmax)

  To evaluate the pharmacokinetics and exposure of 3 different doses of AZD5718

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

• Pharmacokinetic parameter: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)

  To evaluate the pharmacokinetics and exposure of 3 different doses of AZD5718

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

Secondary Outcomes (3)

• Number of subjects with advers event

  Upto 7 weeks

• Pharmacokinetic parameter: AUC

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

• Pharmacokinetic parameter: Cmax

  Day 1: Pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours post dose, Day 2: 24 and 36 hours post dose and Day 3: 48 hours post dose

Study Arms (6)

Arm1: AZD5718 Dose A + AZD5718 Dose B + AZD5718 Dose C

EXPERIMENTAL

Subjects will receive one tablet once daily (QD) of each treatment according to treatment arm. Treatment A: AZD5718 Dose A, Treatment B: AZD5718 Dose B, Treatment C: AZD5718 Dose C, with a minimum washout period of 4 days between each dose administration.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Arm2: AZD5718 Dose A + AZD5718 Dose C + AZD5718 Dose B

EXPERIMENTAL

Subjects will receive one tablet once daily (QD) of each treatment according to treatment arm. Treatment A: AZD5718 Dose A, Treatment C: AZD5718 Dose C, Treatment B: AZD5718 Dose B, with a minimum washout period of 4 days between each dose administration.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Arm3: AZD5718 Dose B + AZD5718 Dose A + AZD5718 Dose C

EXPERIMENTAL

Subjects will receive one tablet once daily (QD) of each treatment according to treatment arm. Treatment B: AZD5718 Dose B, Treatment A: AZD5718 Dose A, Treatment C: AZD5718 Dose C, with a minimum washout period of 4 days between each dose administration.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Arm4: AZD5718 Dose B + AZD5718 Dose C + AZD5718 Dose A

EXPERIMENTAL

Subjects will receive one tablet once daily (QD) of each treatment according to treatment arm. Treatment B: AZD5718 Dose B, Treatment C: AZD5718 Dose C, Treatment A: AZD5718 Dose A, with a minimum washout period of 4 days between each dose administration.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Arm5: AZD5718 Dose C + AZD5718 Dose A + AZD5718 Dose B

EXPERIMENTAL

Subjects will receive one tablet once daily (QD) of each treatment according to treatment arm. Treatment C: AZD5718 Dose C, Treatment A: AZD5718 Dose A, Treatment B: AZD5718 Dose B, with a minimum washout period of 4 days between each dose administration.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Arm6: AZD5718 Dose C + AZD5718 Dose B + AZD5718 Dose A

EXPERIMENTAL

Subjects will receive one tablet once daily (QD) of each treatment according to treatment arm. Treatment C: AZD5718 Dose C, Treatment B: AZD5718 Dose B, Treatment A: AZD5718 Dose A, with a minimum washout period of 4 days between each dose administration.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Interventions

Treatment A DRUG

Subject will be given AZD5718 Dose A tablet once daily

Arm1: AZD5718 Dose A + AZD5718 Dose B + AZD5718 Dose C; Arm2: AZD5718 Dose A + AZD5718 Dose C + AZD5718 Dose B; Arm3: AZD5718 Dose B + AZD5718 Dose A + AZD5718 Dose C; Arm4: AZD5718 Dose B + AZD5718 Dose C + AZD5718 Dose A; Arm5: AZD5718 Dose C + AZD5718 Dose A + AZD5718 Dose B; Arm6: AZD5718 Dose C + AZD5718 Dose B + AZD5718 Dose A

Treatment B DRUG

Subjects will be given AZD5718 Dose B tablet once daily

Arm1: AZD5718 Dose A + AZD5718 Dose B + AZD5718 Dose C; Arm2: AZD5718 Dose A + AZD5718 Dose C + AZD5718 Dose B; Arm3: AZD5718 Dose B + AZD5718 Dose A + AZD5718 Dose C; Arm4: AZD5718 Dose B + AZD5718 Dose C + AZD5718 Dose A; Arm5: AZD5718 Dose C + AZD5718 Dose A + AZD5718 Dose B; Arm6: AZD5718 Dose C + AZD5718 Dose B + AZD5718 Dose A

Treatment C DRUG

Subjects will be given AZD5718 Dose C tablet once daily

Arm1: AZD5718 Dose A + AZD5718 Dose B + AZD5718 Dose C; Arm2: AZD5718 Dose A + AZD5718 Dose C + AZD5718 Dose B; Arm3: AZD5718 Dose B + AZD5718 Dose A + AZD5718 Dose C; Arm4: AZD5718 Dose B + AZD5718 Dose C + AZD5718 Dose A; Arm5: AZD5718 Dose C + AZD5718 Dose A + AZD5718 Dose B; Arm6: AZD5718 Dose C + AZD5718 Dose B + AZD5718 Dose A

Eligibility Criteria

• Age: 18 Years - 55 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.
• Healthy male and/or female subjects aged 18 to 55 years (inclusive at Screening Visit) with suitable veins for cannulation or repeated venipuncture.
• Males must be willing to use appropriate contraception methods.
• Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit (Day -1) must not be lactating and must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria
• Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer'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.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at the Screening Visit and/or admission to the Clinical Unit (Day -1), as judged by the Investigator including:
• Alanine aminotransferase (ALT) \>1.5 x upper limit of normal (ULN).
• Aspartate aminotransferase (AST) \>1.5 x ULN.
• Bilirubin (total) \>1.5 x ULN.
• Gamma glutamyl transpeptidase (GGT) \>1.5 x ULN.
• Any clinically significant abnormal findings in vital signs at the Screening Visit and/or admission to the Clinical Unit (Day -1), as judged by the Investigator.
• Any clinically significant abnormalities on 12 lead ECG at the Screening Visit, as judged by the Investigator.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Known or suspected history of drug abuse, as judged by the Investigator.
• Known or suspected Gilbert's syndrome.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the Investigator.
• Plasma donation within 1 month of the Screening Visit or any blood donation/loss more than 500 mL during the 3 months prior to the Screening Visit.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

London, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The following treatments will be given in crossover design: * Treatment A: AZD5718 Dose A tablet * Treatment B: AZD5718 Dose B tablet * Treatment C: AZD5718 Dose C tablet There will be 6 arms consisting of all possible treatment sequences. The treatment sequence per arm will be: Arm1: ABC Arm2: ACB Arm3: BAC Arm4: BCA Arm5: CAB Arm6: CBA

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: September 12, 2019
• Study Start: September 20, 2019
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2019
• Last Updated: November 15, 2019

Record last verified: 2019-11

Locations

GB (1)