AZD0186 Safety Study

Overseen By AstraZeneca Clinical Study Information Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: GLP-1 RA

Disqualifiers: Gastrointestinal, Hepatic, Renal, Retinal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and tolerability of the new oral drug, AZD0186, in increasing doses. It also examines how the body processes the drug. Participants will receive either AZD0186 or a placebo (a substance with no active drug) for comparison. The trial seeks healthy adults without major health issues, particularly eye or liver problems, and who have not recently used nicotine or illegal drugs. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy adults, it's possible that taking medications could affect your eligibility.

Is there any evidence suggesting that AZD0186 is likely to be safe for humans?

Research has shown that AZD0186 was safe and well-tolerated in earlier studies. AZD0186 affects the GLP-1 receptor, which helps the body manage sugar and fat. In these studies, most participants handled the treatment well, and researchers found no major safety issues.

This trial is in its early stages, focusing on the treatment's safety and tolerability. Researchers are closely monitoring the treatment's safety due to its early phase. This trial will provide more information about any possible side effects. Overall, earlier research offers a positive view of AZD0186's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AZD0186 is unique because it introduces a novel approach in its mechanism of action, which researchers believe could offer a more targeted and efficient treatment option. Unlike many existing treatments that work by broadly affecting the body's systems, AZD0186 specifically targets pathways believed to be central to the condition's progression, potentially leading to more effective outcomes with fewer side effects. Researchers are particularly excited about its potential to significantly improve safety and tolerability compared to standard therapies, which often come with challenging side effects.

What evidence suggests that AZD0186 could be effective?

Research shows that AZD0186 is a promising new treatment that mimics a natural hormone in the body to help control blood sugar levels. Early studies with healthy participants tested AZD0186 at different doses and found potential in affecting these hormone pathways. Although more data is needed, its mechanism suggests usefulness for conditions like type 2 diabetes. However, further research is necessary to confirm this. In this trial, participants will be divided into different cohorts, with some receiving AZD0186 and others a placebo. The trial remains in its early stages, focusing mainly on understanding how the body processes the drug and ensuring its safety in humans. ^{5 6 7 8 9}

Who Is on the Research Team?

Esther Yoon, MD

Principal Investigator

PAREXEL Early Phase Clinical Unit-Los Angeles

Are You a Good Fit for This Trial?

Inclusion Criteria

Provision of signed and dated, written informed consent prior to any study specific procedures.

Provision of signed, written, and dated informed consent for optional genetic/biomarker research.

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).

Exclusion Criteria

You have a history or currently have a gastrointestinal, liver, or kidney disease, or any other medical condition that can affect how your body processes drugs.

You have a medical condition that may put you at risk or affect your ability to participate in the study.

You have had retinal detachment in one or both of your eyes in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive single ascending doses of AZD0186 and are monitored for safety and pharmacokinetics

3 days

In-residence from Day -2 to Day 3

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Follow-up visit 7 or 14 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• AZD0186
• Placebo

How Is the Trial Designed?

Group I: Cohort 4 (healthy volunteers - food effect) Experimental Treatment 2 Interventions

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.

Group II: Cohort 3 (healthy Chinese volunteers) Experimental Treatment 2 Interventions

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.

Group III: Cohort 2 (healthy Japanese volunteers) Experimental Treatment 2 Interventions

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.

Group IV: Cohort 1 (healthy volunteers) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41015846/

Preclinical evaluation and first-in-human phase 1 trial of ... AZD0186 was evaluated at 4 oral single ascending dose levels (5, 15, 50, and 150 mg) in healthy participants. Results showed that AZD0186 is ...

2. researchgate.net researchgate.net/publication/395057589_Preclinical_Evaluation_and_First-In-Human_Phase_1_Trial_of_AZD0186_a_Novel_Oral_Small_Molecule_Glucagon-Like_Peptide-1_Receptor_Agonist

Preclinical Evaluation and First-In-Human Phase 1 Trial of ... Preclinical Evaluation and First-In-Human Phase 1 Trial of AZD0186, a Novel, Oral Small Molecule Glucagon-Like Peptide-1 Receptor Agonist.

3. astrazeneca.com astrazeneca.com/content/dam/az/PDF/2022/fy/Full-year-and-Q4-2022-results-clinical-trials-appendix.pdf

Clinical Trials Appendix reducing agent on PK of AZD5055 in healthy volunteers. • Primary endpoints: bioavailability and. PK parameters. • FPCD: Q4 2022. • Data anticipated: H1 2023. On.

4. researchgate.net researchgate.net/publication/371541425_Tolerability_safety_and_pharmacodynamics_of_oral_small-molecule_glucagon-like_peptide-1_receptor_agonist_danuglipron_for_type_2_diabetes_A_12-week_randomized_placebo-controlled_Phase_2_study_comparing

A 12‐week, randomized, placebo‐controlled, Phase 2 ... [5][6][7][8] Here, we report results of a randomized, double-blind, placebo-controlled Phase 2b study to assess the efficacy, safety, and ...

5. reporter.nih.gov reporter.nih.gov/search/KokC7RLftkGyBqlHC3-bow/project-details/10825007

RePORT ⟩ RePORTER We're sorry but RePORTER doesn't work properly without JavaScript enabled. Please enable it to continue.

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8740C00001/

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

7. jpet.aspetjournals.org jpet.aspetjournals.org/article/S0022-3565(25)39896-4/fulltext

Preclinical evaluation and first-in-human phase 1 trial of ... Findings demonstrate that AZD0186 is a potent agonist of the GLP-1R, and the first-in-human study indicates a favorable safety and tolerability profile.

8. s3.amazonaws.com s3.amazonaws.com/ctr-med-7111/D8740C00001/a506b377-16f9-445b-bb42-6620c0728261/9e21adf1-7eb3-47e9-9eea-11b170cb0df4/D8740C00001_Redacted_CSR_Synopsis-v1.pdf

Clinical Study Report AZD0186D8740C00001 Healthy male and female (of non-child-bearing potential) subjects, 18 to 55 years of age, who had a body mass index of 18 to 32 kg/m² (inclusive) ...

9. app.trialscreen.org app.trialscreen.org/trials/phase-1-type-2-diabetes-to-assess-safety-tolerability-pharmacokinetics-trial-nct05694741

A Study to Assess Safety, Tolerability, and ... This study evaluates AZD0186, an investigational drug, in healthy adults to determine its safety, tolerability, and pharmacokinetics.