AZD6234 for Obesity

No longer recruiting at 1 trial location

Overseen By AstraZeneca Clinical Study Information Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Disqualifiers: Diabetes, Cardiovascular disease, Severe allergy, others

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

Compensation: Varies

Number of Visits: 54

Duration: 8 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AZD6234, for individuals who are overweight or obese. The goal is to determine the safety and effectiveness of AZD6234 at various doses. Several groups will participate, with each group receiving either the treatment or a placebo to compare effects. The trial seeks healthy men and women with a body mass index (BMI) between 25 and 35, without major health issues affecting daily life. As a Phase 1 trial, this research aims to understand how AZD6234 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research shows that AZD6234 has undergone testing to assess its safety and tolerability at various doses. In these studies, participants received the treatment either as an injection under the skin or directly into a vein. Most participants tolerated the treatment well, experiencing only mild side effects. As this is an early phase trial, the primary goal is to ensure the treatment's safety for people. Researchers carefully monitor for any negative reactions. A treatment in this phase remains under evaluation to confirm its safety for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

AZD6234 is unique because it introduces a novel approach to treating obesity with its innovative delivery methods and potential to offer new benefits over current treatments. Unlike standard options, such as lifestyle changes and medications like orlistat or GLP-1 receptor agonists, AZD6234 is administered through subcutaneous (SC) or intravenous (IV) injections, which may allow for more controlled dosing and potentially quicker absorption. Researchers are excited about its potential to effectively manage weight by possibly targeting new pathways involved in obesity, which could lead to improved outcomes for patients who do not respond well to existing therapies.

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

Research shows that AZD6234 might help people who are overweight or obese lose weight. In earlier studies, participants taking AZD6234 lost more weight than those who did not. For instance, some participants lost 10% or more of their starting weight over 26 weeks. This trial will evaluate the effectiveness of AZD6234 in various treatment arms, with participants receiving different doses of AZD6234 or a placebo. These findings suggest that AZD6234 could effectively help reduce body weight. However, like any new treatment, further research is needed to confirm these results and ensure safety. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for healthy, overweight or obese adults aged 18 to 55 who are not of childbearing potential. Women must be postmenopausal or surgically sterile. Participants should have a BMI between 25 and 35 kg/m2, weigh at least 50 kg, and have good veins for drawing blood. Japanese heritage participants need both parents and all grandparents to be Japanese.

Inclusion Criteria

You are a Japanese citizen, defined as having both parents and four grandparents who are Japanese

(i) Post menopausal 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 post menopausal range.

(ii) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

Exclusion Criteria

History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study, including: (i) Gastroparesis (or similar) requiring treatment, or (ii) Previous surgery of the upper gastrointestinal tract, or (iii) Cardiovascular disease, including but not limited to sick sinus syndrome, valvular disease, and cardiomyopathy, or (iv) Neuromuscular or neurogenic disease, or (v) Severe vitamin D deficiency < 12 ng/dL (as assessed by screening laboratory results or history), or (vi) Type 1 or type 2 diabetes mellitus

You have a history or current condition affecting your stomach, liver, kidneys, or any other condition that could affect how your body processes medication.

You follow a vegan diet or have specific dietary restrictions for medical reasons.

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 AZD6234 and are monitored in the Clinical Unit

8 days

Inpatient stay from Day -3 to Day 5

Outpatient Monitoring

Weekly outpatient visits for blood sample collection, ECGs, and adverse events recording

5 weeks

Weekly visits on Days 8, 15, 22, 29, and 36

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Follow-up visit on Day 43

What Are the Treatments Tested in This Trial?

Interventions

• AZD6234

Trial Overview The study tests the safety, tolerability, and how the body processes AZD6234 in single doses compared to a placebo. Some participants will also receive acetaminophen to assess interactions. The trial involves people receiving one dose of either AZD6234 or placebo in varying amounts.

How Is the Trial Designed?

Group I: Cohort 8 Experimental Treatment 3 Interventions

Participants will receive AZD6234 via SC injection and matching volumes of placebo as a solution via SC injection

Group II: Cohort 7 Experimental Treatment 3 Interventions

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC injection

Group III: Cohort 6 Experimental Treatment 3 Interventions

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC injection

Group IV: Cohort 5 Experimental Treatment 3 Interventions

One dose level for SC administration is planned to be investigated for Japanese participants only

Group V: Cohort 4 Experimental Treatment 3 Interventions

Participants will receive single ascending doses of AZD6234 via IV injection and matching volumes of the placebo as a solution via IV injection

Group VI: Cohort 3 Experimental Treatment 3 Interventions

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC injection

Group VII: Cohort 2 Experimental Treatment 3 Interventions

Participants will receive a single dose of AZD6234 via an SC injection and matching volume of the placebo as a solution via SC injection

Group VIII: Cohort 1 Experimental Treatment 3 Interventions

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC

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

Published Research Related to This Trial

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]

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]

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05511025

Study Details | NCT05511025 | Assess the Safety, ... A study in healthy male and female participants of non-childbearing potential who are overweight or obese.

5. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8460C00004

A weight loss study evaluating subcutaneous treatment ... The purpose of this study is to determine whether treatment with AZD9550 when given in combination with AZD6234 as once weekly subcutaneous (SC) injections ...

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 ...