AZD6234 for Obesity

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)

142 Participants Needed

Trial Summary

What is the purpose of this trial?

A study in healthy male and female participants of non-childbearing and childbearing potential who have overweight or obesity

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.

How does the drug AZD6234 for obesity differ from other treatments?

AZD6234 is unique because it may target the melanocortin 4 receptor (MC4R), which is involved in regulating appetite and body weight, potentially offering a new approach for individuals with genetic mutations in this receptor that contribute to obesity. ^{1 2 3 4 5}

Eligibility Criteria

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

I am between 18 and 55 years old with veins suitable for repeated needle insertions.

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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 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]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Current updates in the medical management of obesity. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Melanocortin 4 receptor mutations in obese Czech children: studies of prevalence, phenotype development, weight reduction response, and functional analysis. [2007]