AZD6234 for Obesity

(APRICUS Trial)

Recruiting in Palo Alto (17 mi)

+43 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: AstraZeneca

Prior Safety Data

Trial Summary

What is the purpose of this trial?

A Phase IIb Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of AZD6234 compared with placebo, given once a week as subcutaneous injection for 36 weeks, in male and female participants of at least 18 years of age who are living with obesity (body mass index \[BMI\] ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) and at least one weight-related comorbidity

Do I need to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken any weight loss medication in the last 3 months before the trial.

What data supports the idea that AZD6234 for Obesity is an effective drug?

The available research does not provide specific data on the effectiveness of AZD6234 for treating obesity. Instead, it discusses other treatments like bariatric surgery and acupuncture combined with diet control. These treatments are shown to help with weight loss and improve quality of life, but there is no direct comparison or mention of AZD6234 in the context of obesity treatment. ^{1 2 3 4 5}

What safety data is available for AZD6234 in treating obesity?

The provided research does not specifically mention AZD6234 or its variants. However, it discusses the safety concerns associated with anti-obesity medications in general, highlighting serious adverse events such as cardiovascular and kidney complications, nausea, vomiting, dizziness, and headaches. The studies emphasize the importance of monitoring the safety of anti-obesity medications due to potential severe adverse events, including life-threatening conditions and hospitalizations. For specific safety data on AZD6234, further investigation into clinical trial results or specific studies on this drug would be necessary. ^{6 7 8 9 10}

Is the drug AZD6234 a promising treatment for obesity?

The drug AZD6234 is considered promising for obesity because it targets the melanocortin 4 receptor (MC4R), which is linked to obesity. This approach could help reduce weight by affecting appetite and body weight regulation, offering a new option for those struggling with obesity. ^{11 12 13 14 15}

Research Team

Eligibility Criteria

This trial is for adults at least 18 years old who are living with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) and have at least one weight-related health issue. Specific eligibility criteria details were not provided.

Inclusion Criteria

A stable body weight for 3 months prior to Screening (±5% body weight change)

I am 18 years old or older.

My BMI is 30 or higher, or it's 27 or higher with a weight-related health issue.

Exclusion Criteria

I have had or plan to have weight loss surgery or a device fitted.

My obesity is caused by an endocrine disorder like Cushing's or Prader-Willi syndrome.

I have taken weight loss medication in the last 3 months.

Treatment Details

Interventions

• AZD6234 (Other)

Trial Overview The study tests AZD6234, a potential new medication for weight management, against a placebo. Participants will receive either the real drug or placebo as a weekly subcutaneous injection for 32 weeks in this double-blind study.

Participant Groups

Group I: Arm 3 Experimental Treatment 1 Intervention

Dose 3

Group II: Arm 2 Experimental Treatment 1 Intervention

Dose 2

Group III: Arm 1 Experimental Treatment 1 Intervention

Dose 1

Group IV: Arm 4 Placebo Group 1 Intervention

Placebo - Dose matched with each Experimental arm

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

In a study of 45 participants with simple obesity, a triple therapy approach combining auricular acupuncture, diet control, and aerobic exercise counseling over eight weeks led to an average weight loss of 4.4 kg and a 5.6% reduction in body fat, with an overall effectiveness rate of 86.7%.

The treatment showed good long-term maintenance of weight loss, with only 6.7% of participants regaining more than 1.5 kg after one month, and 18.9% after one year, indicating that adherence to the therapy was crucial for sustained results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of triple therapy for obesity. Huang, MH., Yang, RC., Hu, SH.[2014]

Bariatric surgery, specifically SLEEVE Vertical Gastrectomy and Roux-en-Y Gastric Bypass, resulted in a significant average excess weight loss of 69.35% among 103 patients, with a follow-up period of approximately 42 months.

The surgery led to high rates of resolution for comorbidities such as sleep apnea (90.2%), diabetes (80.7%), and hypertension (70.8%), while also improving quality of life for 93.2% of patients according to the BAROS protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of quality of life, weight loss and comorbidities of patients undergoing bariatric surgery. Castanha, CR., Tcbc-Pe, ÁABF., Castanha, AR., et al.[2022]

In a study of 334 participants with simple obesity, those receiving acupuncture combined with diet control (observation group) showed a total effective rate of 91.8%, significantly higher than the 75.7% and 73.1% in the other control groups.

The acupuncture and diet control approach not only resulted in better weight loss outcomes but also had a lower rate of weight regain after one year compared to diet control alone, indicating its potential as a more sustainable treatment for obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation on acupuncture combined with diet control for treatment of simple obesity]. Chen, ZX.[2009]

The treatment of obesity aims to prevent complications, achieve realistic weight loss, and ensure psychological well-being, highlighting the need for personalized approaches rather than one-size-fits-all solutions.

Effective management includes a combination of physical exercise, dietary counseling, medication, and sometimes surgery, with psychological support being essential for overall patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of obesity]. Basdevant, A.[2006]

A comprehensive analysis of the FDA Adverse Event Reporting System revealed 18,675 unique adverse event reports linked to anti-obesity medications (AOMs) among 15,143 patients, highlighting significant safety concerns.

Serious adverse events included a fatality ratio of 4.9%, with cardiovascular complications being particularly prevalent, accounting for 31% of AEs related to phentermine, and indicating a need for ongoing safety monitoring of AOMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. Alsuhibani, A., Alrasheed, M., Gari, M., et al.[2022]

A total of 25 anti-obesity medications were withdrawn between 1964 and 2009, primarily due to adverse reactions related to their effects on monoamine neurotransmitters, with 80% of withdrawals supported by case reports.

The most common reasons for withdrawal included psychiatric disturbances, cardiotoxicity, and drug dependence, raising concerns about the safety of using medications that target neurotransmitters for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. Onakpoya, IJ., Heneghan, CJ., Aronson, JK.[2022]

Obesity is a significant healthcare burden linked to chronic diseases like hypertension and diabetes, driven by factors such as diet, physical inactivity, and genetic predisposition.

Current obesity treatments have focused on reducing appetite or nutrient absorption but have had limited success and safety concerns, highlighting the need for new, effective, and safe pharmacotherapies, which are being explored across four main categories of drug action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiobesity therapy: emerging drugs and targets. Das, SK., Chakrabarti, R.[2019]

Lorcaserin was found to have a significant association with valvular disorders, indicating a potential cardiovascular safety concern, while no such signals were detected for other recently approved antiobesity drugs like naltrexone-bupropion and phentermine.

The study analyzed a large dataset of 6,787,840 adverse event reports from the FDA, focusing on cardiovascular outcomes over a five-year period, highlighting the importance of ongoing monitoring for safety in antiobesity medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cardiovascular safety of antiobesity drugs-analysis of signals in the FDA Adverse Event Report System Database. Gorelik, E., Gorelik, B., Masarwa, R., et al.[2021]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Preliminary results of triple therapy for obesity. [2014]

2. Brazil pubmed.ncbi.nlm.nih.gov

Evaluation of quality of life, weight loss and comorbidities of patients undergoing bariatric surgery. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Clinical observation on acupuncture combined with diet control for treatment of simple obesity]. [2009]

4. France pubmed.ncbi.nlm.nih.gov

[Treatment of obesity]. [2006]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Patient Perspective in Obesity Surgery: Goals for Weight Loss and Improvement of Body Shape in a Prospective Cohort Study. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Serious adverse events reported for antiobesity medicines: postmarketing experiences from the EU adverse event reporting system EudraVigilance. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. [2022]

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

Antiobesity therapy: emerging drugs and targets. [2019]

10. England pubmed.ncbi.nlm.nih.gov

The cardiovascular safety of antiobesity drugs-analysis of signals in the FDA Adverse Event Report System Database. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

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

12. 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]

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

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

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

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

15. 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]