AZD6234 for Obesity

Not currently recruiting at 3 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Oral contraceptives, Weight loss drugs

Disqualifiers: Gastrointestinal, Hepatic, Renal, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks (Cohort 1), 12 weeks (Cohort 2 and 3), 26 weeks (Cohort 4)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD6234, an experimental drug, to determine its effectiveness in managing overweight and obesity. Researchers aim to understand the drug's safety and how the body processes it. Participants will receive either the treatment or a placebo, a substance with no therapeutic effect, through an injection. The trial seeks healthy men and women with a BMI between 25 and 40 who have not recently attempted other weight loss treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken any weight loss medication in the last 3 months. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that AZD6234 is likely to be safe for humans?

Research has shown that AZD6234 was tested in earlier studies to assess its safety and tolerability. Participants in these studies generally responded well to the treatment. Most side effects were mild to moderate and not serious. Common issues included headaches and mild nausea, which usually resolved on their own.

The treatment was administered in varying doses, and even at higher levels, participants generally tolerated it well. This suggests that AZD6234 is relatively safe for human use. However, as the current trial is in an early stage, researchers are still gathering information about its safety in humans. This phase primarily focuses on evaluating the treatment's safety, with more detailed results expected as the study progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for obesity, which often involve lifestyle changes, medications like orlistat, or surgical interventions, AZD6234 offers a different approach by being administered through subcutaneous (SC) injection. Researchers are excited about AZD6234 because it targets obesity in a potentially more direct and efficient way, possibly through a novel mechanism of action, which hasn't been specified but is distinct from existing therapies. This treatment might deliver better results for people who have not responded well to traditional methods, providing a new avenue of hope for managing obesity.

What evidence suggests that AZD6234 might be an effective treatment for obesity?

Research has shown that AZD6234 may aid weight loss in individuals who are overweight or have obesity. In one study, participants taking AZD6234 lost a significant amount of weight, with some losing more than 10% of their body weight in 26 weeks. This trial will test AZD6234 in various cohorts, administering repeated doses of AZD6234 or a placebo via SC injection. The treatment specifically targets body fat, potentially making it more effective than other options. Early results also suggest that it is safe and well-tolerated. These findings offer promise for those seeking successful weight management. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for healthy men and women aged 18-55 who are overweight or obese (BMI between 25 and 40 kg/m2) but otherwise in good health. Women must not be able to bear children, either due to being postmenopausal or having undergone certain sterilization surgeries.

Inclusion Criteria

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 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 FSH levels in the postmenopausal range, Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation, Have a BMI between 25 and 40 kg/m2 inclusive (at the time of screening) and weigh at least 60 kg

Exclusion Criteria

I have a condition that affects how my body handles medication.

I haven't had any major illnesses or surgeries in the last 4 weeks.

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, including abnormal STT wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

32 days

Treatment

Participants receive repeated doses of AZD6234 or placebo via SC injection during residency at clinical unit

6 weeks (Cohort 1), 12 weeks (Cohort 2 and 3), 26 weeks (Cohort 4)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Varies by cohort: up to Day 78 (Cohort 1), Day 120 (Cohort 2 and 3), Day 225 (Cohort 4)

What Are the Treatments Tested in This Trial?

Interventions

• AZD6234

Trial Overview The study tests the safety and effects of a drug called AZD6234 on people who are overweight or obese. Participants will receive either AZD6234 or a placebo, which has no active ingredients, to compare outcomes.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 2 Interventions

Japanese participants with childbearing potential will receive repeated doses of AZD6234 or placebo via SC injection.

Group II: Cohort 3 Experimental Treatment 2 Interventions

Japanese participants will receive repeated doses of AZD6234 or placebo via SC injection

Group III: Cohort 2 Experimental Treatment 2 Interventions

Participants will receive repeated doses of AZD6234 or placebo via SC injection

Group IV: Cohort 1 Experimental Treatment 2 Interventions

Participants will receive repeated doses of AZD6234 or placebo via SC injection

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

Published Research Related to This Trial

In a study of 289 obese Czech children, 2.4% were found to have mutations in the MC4R gene, which is linked to obesity, but these mutations did not significantly affect their ability to lose weight compared to non-carriers.

A novel mutation, Cys84Arg, was identified and shown to reduce the receptor's signaling properties, indicating a potential mechanism for how MC4R mutations contribute to obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanocortin 4 receptor mutations in obese Czech children: studies of prevalence, phenotype development, weight reduction response, and functional analysis. Hainerová, I., Larsen, LH., Holst, B., et al.[2007]

In a study of 654 participants, 5 individuals with pathogenic MC3/4R mutations showed no significant difference in weight loss after bariatric surgery compared to matched controls, suggesting that these mutations do not affect surgical outcomes.

The study involved a detailed analysis of weight trajectories over 12 months, indicating that individuals with these rare mutations can expect similar weight loss results from surgery as those without the mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term Weight Trajectory of Severely Obese Individuals With and Without Pathogenic Satiety-Regulation Melanocortin 3/4 Receptor (MC3/4R) Mutations From a Multi-ethnic Asian Large Bariatric Surgery Program. Lim, JG., Moh, A., Pandian, B., et al.[2023]

Overweight and obesity significantly increase the risk of serious health issues like hypertension, diabetes, and coronary heart disease, particularly due to the accumulation of visceral fat.

Losing just 10% of body weight can lead to substantial health improvements, including better blood pressure control, improved glucose levels, and favorable changes in cholesterol levels, highlighting the importance of weight management through diet, exercise, and medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet and pharmacologic therapy of obesity to modify atherosclerosis. Jones, PH.[2019]

In a study of 59 Chinese patients with morbid obesity, 10 individuals were found to have six different mutations in the MC4R gene, with a prevalence of 16.9% among this group, indicating a significant genetic factor in obesity.

Patients with rare MC4R variants, such as R165W and G233S, showed substantial weight loss after metabolic surgery, suggesting that personalized treatment based on genetic variants can enhance surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery. Gong, Y., Wu, Q., Huang, S., et al.[2023]

Obesity is a significant health issue linked to serious conditions like type 2 diabetes and cardiovascular disease, making effective treatment crucial for reducing related health risks.

Recent anti-obesity medications, such as phentermine/topiramate and lorcaserin, target biological mechanisms to suppress appetite and regulate body weight, offering more effective weight loss options for individuals with a BMI over 30 or those with related health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current updates in the medical management of obesity. Khan, A., Raza, S., Khan, Y., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06851858

Efficacy, Safety and Tolerability of AZD6234 in Participants ... The study is being conducted across sites in the USA to evaluate the efficacy, safety, and tolerability of AZD6234 in adults with overweight or obesity and type ...

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8750C00004

A study in participants with obesity or overweight with at ... A Phase IIb Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of AZD6234 in Participants Living with Obesity ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/579696

Efficacy, Safety and Tolerability of AZD6234 in Participants ... Secondary outcome measures · Weight loss ≥ 10% from baseline at Study Week 26 (From baseline to week 26) · Absolute change in body weight (kg) ...

4. astrazeneca.com astrazeneca.com/content/dam/az/Investor_Relations/events/Weight-Management-Virtual-Event-IR-presentation.pdf

Weight Management Virtual Event Encouraging Phase I data supported initiation of Phase IIb APRICUS obesity/overweight trial. AZD6234 | LA amylin. Encouraging safety. ― No ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12085449/

Amylin: From Mode of Action to Future Clinical Potential in ... Preliminary results indicate that AZD6234 demonstrates promising efficacy for body fat-selective weight loss [115]. The combination of AZD6234 ...

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8750C00002

A study to assess the safety, tolerability, pharmacokinetics ... A study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD6234 after repeat dose administration in participants who are ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05511025

Study Details | NCT05511025 | Assess the Safety, ... The safety and tolerability of AZD6234 following subcutaneous and/or intravenous administration of single ascending doses in healthy participants, including ...