A Study to Evaluate Effect of AZD6234 as an Adjunct to Incretin-based Therapies in Adult Participants With Obesity or Overweight With Weight-related Comorbidity With or Without Type 2 Diabetes Mellitus

Phase 3RecruitingNCT07776509

AstraZeneca500 enrolled

Overview

The study will evaluate how well AZD6234 works and how safe it is in adults with excess weight or obesity. Efficacy of AZD6234 will be compared to placebo in percent body weight change from baseline at 68 weeks of treatment.

This is a Phase III, global, randomised, parallel-group, double-blind, multicentre study to assess the efficacy and safety of AZD6234 as an adjunct to incretin-based therapies, compared with placebo in adults with obesity or overweight with at least one weight-related comorbidity and with or without Type 2 Diabetes Mellitus (T2DM). Eligible participants will be randomised to either receive AZD6234 or matching placebo respectively. Study treatment (AZD6234 or placebo) will be added on to the participant's stable dose of background incretin-based therapies.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

500

Conditions

Obesity or Overweight Weight-Related Comorbidity With/Without Diabetes Mellitus, Type 2

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males \& females (inclusive of all gender identities) age ≥18 years * BMI ≥ 30 kg/m2 OR BMI ≥ 27 kg/m2 with at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, heart failure, chronic kidney disease, metabolic dysfunction associated steatotic liver disease, osteoarthritis of the knee, or stress urinary incontinence * For participants with T2DM only: * Diagnosed with T2DM ≥ 90 days prior to Screening * HbA1c value at Screening of ≥6.0% (42 mmol/mol) and ≤9.0% (75 mmol/mol) managed with diet and exercise alone or with a stable dose of any oral glycaemic-lowering agent and/or incretin-based medication * Receiving a stable dose of incretin- based medications at a dose level that is sufficient for chronic weight management for at least 3 months prior to Screening and Randomisation. * Stable body weight (≤ 3% body weight change) for at least 3 months prior to Randomisation * History of at least one self-reported unsuccessful attempt to lose body weight in their lifetime Exclusion Criteria: * Obesity primarily caused by other endocrine disorders * Type 1 diabetes mellitus * Significant hepatobiliary disease and/or any of the following results at Screening: * ALT ≥ 3.0 × ULN * AST ≥ 3.0 × ULN * TBL \> 1.5 × ULN (except for cases of known Gilbert's Syndrome) * Use of insulin therapy for T2DM within 3 months prior to screening

Outcomes

Primary Outcomes

Percent change in body weight from baseline at 68 weeks of treatment

To evaluate the effect of AZD6234 as compared to placebo as an adjunct to incretin-based therapies in percent body weight change

Time frame: 68 weeks

Secondary Outcomes

Percent change in body weight from baseline at 68 weeks of treatment

To evaluate the effect of AZD6234 as compared to placebo as an adjunct to incretin-based therapies in percent body weight change in the T2DM and non-T2DM sub-populations separately

Time frame: 68 weeks

Absolute change in weight (kg) from baseline at 68 weeks of treatment

To evaluate the effect of AZD6234 as compared to placebo as an adjunct to incretin-based therapies on the absolute change in weight in the full population and in the T2DM and non-T2DM sub-populations separately

Time frame: 68 weeks

Achievement of at least 5% body weight loss from baseline at 68 weeks of treatment

To evaluate the effect of AZD6234 as compared to placebo as an adjunct to incretin-based therapies in body weight loss of at least 5% in the full population and in the T2DM and non T2DM sub-populations separately

Time frame: 68 weeks

Achievement of at least 10% body weight loss from baseline at 68 weeks of treatment

To evaluate the effect of AZD6234 as compared to placebo as an adjunct to incretin-based therapies in body weight loss of at least 10% in the full population and in the T2DM and non T2DM sub-populations separately

Time frame: 68 weeks

Change in waist circumference (cm) from baseline at 68 weeks of treatment

To evaluate whether AZD6234 as an adjunct to incretin-based therapies on the waist circumference in the full population and in the T2DM and non-T2DM sub-populations separately

Time frame: 68 weeks

Percent change in triglycerides from baseline at 68 weeks of treatment

To evaluate the effect of AZD6234 as compared to placebo as an adjunct to incretin-based therapies on triglycerides percent change

Time frame: 68 weeks

Change in systolic blood pressure (mmHg) from baseline at 68 weeks of treatment

To evaluate the effect of AZD6234 as compared to placebo as an adjunct to incretin-based therapies on the systolic blood pressure change

Time frame: 68 weeks

Change in HbA1c from baseline at 68 weeks of treatment

For participants with T2DM only: to evaluate the effect of AZD6234 as an adjunct to incretin-based therapies on HbA1c change in the T2DM sub population only

Time frame: 68 weeks

A Study to Evaluate Effect of AZD6234 as an Adjunct to Incretin-based Therapies in Adult Participants With Obesity or Overweight With Weight-related Comorbidity With or Without Type 2 Diabetes Mellitus

Overview

Conditions

Interventions

Eligibility

Locations (96)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts