AZD6234 for Obesity

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

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called AZD6234 in healthy adults who are overweight or obese. The study aims to find the best dose and method of giving the drug by testing it under the skin and directly into a vein. Participants will be monitored closely to see how their bodies react.

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.

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, 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 States pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

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]