A Study to Assess Safety, Tolerability, and Pharmacokinetics of AZD0186

NCT05694741 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: D8740C00001
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the safety, tolerability, and pharmacokinetics of AZD0186 following single ascending doses (SAD) via oral administration in healthy adult participants.

Conditions

Type 2 Diabetes

Keywords

Type 2 Diabetes; Hyperglycemia; Glucagon-like peptide-1 receptor agonists

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs), and Serious Adverse Events (SAEs)

  The safety and tolerability of AZD0186 following oral single ascending doses in healthy subjects (Part 1 and Part 4), in healthy Japanese subjects (Part 2), and in healthy Chinese subjects (Part 3) will be assessed.

  Up to the Follow-up Visit (approximately 6 weeks)

Secondary Outcomes (3)

• Area under plasma concentration-time curve from zero to infinity (AUCinf)

  Day 1 to Day 3

• Area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUClast)

  Day 1 to Day 3

• Maximum observed concentration (Cmax)

  Day 1 to Day 3

Study Arms (4)

Cohort 1 (healthy volunteers)

EXPERIMENTAL

The planned number of cohorts is up to 6 cohorts; additional cohorts may be included if it is considered necessary to repeat a dose level or if additional dose steps are required for safety purposes. Six subjects will receive AZD0186, and two subjects will receive placebo.

Drug: AZD0186; Drug: Placebo

Cohort 2 (healthy Japanese volunteers)

EXPERIMENTAL

The planned number of Japanese cohorts is 1, but more than 1 cohort may be included if the SRC considers it necessary to repeat a dose level or if additional dose steps are required. No sentinel dosing will be performed for the Japanese cohort.

Drug: AZD0186; Drug: Placebo

Cohort 3 (healthy Chinese volunteers)

EXPERIMENTAL

The planned number of Chinese cohorts is 1, but more than 1 cohort may be included if it is considered necessary to repeat a dose level or if additional dose steps are required. No sentinel dosing will be performed for the Chinese cohort.

Drug: AZD0186; Drug: Placebo

Cohort 4 (healthy volunteers - food effect)

EXPERIMENTAL

One of the Part 1 cohorts (planned for Cohort 6, can be updated pending emerging data) will continue into the food-effect part after a washout period. This part will be initiated after SRC review of all available data from preceding cohorts in this study.

Drug: AZD0186; Drug: Placebo

Interventions

AZD0186 DRUG

Subjects will receive AZD0186 orally.

Cohort 1 (healthy volunteers); Cohort 2 (healthy Japanese volunteers); Cohort 3 (healthy Chinese volunteers); Cohort 4 (healthy volunteers - food effect)

Placebo DRUG

Subjects will receive placebo orally.

Cohort 1 (healthy volunteers); Cohort 2 (healthy Japanese volunteers); Cohort 3 (healthy Chinese volunteers); Cohort 4 (healthy volunteers - food effect)

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 female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
• 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-childbearing potential, confirmed at the Screening Visit.
• Have a BMI between:
• Part 1: 18 to 32 kg/m2 inclusive,
• Part 2 and Part 3: 18 to 32 kg/m2 inclusive,
• and weigh at least 50 kg (males and females).
• Provision of signed, written, and dated informed consent for optional genetic/biomarker research.
• For the healthy Japanese cohort (Part 2): healthy subjects are to be Japanese (eg, natives of Japan or Japanese Americans), defined as having both parents and 4 grandparents who are Japanese.
• For the healthy Chinese cohort (Part 3): healthy male and female (of non-childbearing potential) healthy Chinese subjects for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years.

You may not qualify if:

• History of any clinically important disease or disorder which may either put the healthy subject at risk because of participation in the study,or influence the results or the healthy 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.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
• Presence of any retinal (including intraretinal) abnormality detected by ophthalmological examination including indirect ophthalmoscopy, fundoscopy or OCT.
• Presence of any factors that predispose to retinal detachment including lattice degeneration, retinal hole, or high myopia (-10 diopters or higher) found on ophthalmological examination.
• History of retinal detachment in either eye.
• History of treated or untreated retinal holes.
• Any clinically important abnormalities across the ophthalmological examinations.
• Any laboratory values with the following deviations:
• Alanine aminotransferase \> ULN
• Aspartate aminotransferase \> ULN
• eGFR \< 90 mL/minute/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula)
• White blood cell count \< LLN
• Hemoglobin \< LLN
• Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

Related Links

• D8740C00001\_Redacted\_CSR Synopsis
• D8740C00001\_link to the results already presented on AZCT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Esther Yoon, MD

  PAREXEL Early Phase Clinical Unit-Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Masking Details: Sponsor-open
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-control

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 23, 2023
• Study Start: December 20, 2022
• Primary Completion: May 10, 2023
• Study Completion: May 10, 2023
• Last Updated: December 13, 2024

Record last verified: 2024-12

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 refer 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 (1)