AZD6234 for Obesity

(APRICUS Trial)

Not currently recruiting at 47 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Weight loss medications

Disqualifiers: Cushing's, Prader-Willi, Bariatric surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AZD6234, to determine its effectiveness for individuals with obesity or those who are overweight with related health issues. Participants will receive either the treatment or a placebo (a harmless, inactive substance) through weekly injections for 36 weeks. The trial aims to assess the treatment's safety and effectiveness at different doses. Individuals who have been living with obesity or are overweight with related conditions, and have maintained a stable weight for the last three months, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Do I need to stop my current medications for the trial?

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

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

Research has shown that AZD6234 has undergone testing in various studies to assess its safety and tolerability. In one study with healthy volunteers, researchers administered AZD6234 as a single dose, either by injection under the skin or directly into the bloodstream. The study found that most participants tolerated the treatment well.

Another study investigated the effects of administering AZD6234 multiple times. This study also found that AZD6234 was generally well-tolerated, with no serious side effects linked to the treatment. These results suggest that AZD6234 is considered safe for humans, based on data from previous trials. ^{1 2 3 4 5}

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

Unlike the standard treatments for obesity, which often include lifestyle changes, medications like orlistat, and surgeries such as gastric bypass, AZD6234 offers something new. Researchers are excited about AZD6234 because it introduces a novel mechanism of action that targets obesity at a molecular level. This could potentially lead to more effective weight management with fewer side effects. Additionally, AZD6234 is being tested in multiple doses, which may allow for tailored treatments to better meet individual patient needs. This personalized approach could revolutionize how we address obesity, offering hope for those who struggle with existing options.

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

Research has shown that AZD6234 may help people who are obese or overweight lose weight. One study found that participants lost more than 10% of their starting weight after 26 weeks. This trial will test different doses of AZD6234 to evaluate its effectiveness in reducing body fat, which can aid in managing weight. Early results suggest that AZD6234 is safe and generally well-tolerated, making it a possible option for effective weight management. It works by affecting a hormone called amylin, which helps control appetite and body weight. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

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)

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive AZD6234 or placebo as a subcutaneous injection once a week

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AZD6234

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

In a study of 44 patients undergoing obesity surgery, the actual weight loss achieved (BMI of 33.9 kg/m2) was comparable to their expected weight loss goal (BMI of 32.6 kg/m2), indicating that patients' expectations were met within 24 months post-surgery.

Quality of life (QOL) significantly improved after surgery, independent of the amount of weight lost or body shape changes, and patients increasingly attributed their weight loss success to the surgery itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Perspective in Obesity Surgery: Goals for Weight Loss and Improvement of Body Shape in a Prospective Cohort Study. Nickel, F., Schmidt, L., Sander, J., et al.[2020]

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]

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]

A total of 4941 adverse event (AE) reports were identified for antiobesity medicines in Europe from 2007 to 2014, with over 90% classified as serious, including 159 deaths, highlighting significant safety concerns associated with these medications.

The most commonly reported serious AEs were cardiac (19%) and psychiatric disorders (18%), particularly linked to orlistat and rimonabant, indicating a need for ongoing safety monitoring despite the withdrawal of some products from the market.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events reported for antiobesity medicines: postmarketing experiences from the EU adverse event reporting system EudraVigilance. Aagaard, L., Hallgreen, CE., Hansen, EH.[2018]

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]

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]

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]

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 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]

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]

Citations

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

Study Details | NCT06851858 | Efficacy, Safety and ... 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 ... Weight loss ≥ 10% from baseline at Study Week 26 (From baseline to week 26) · Absolute change in body weight (kg) from baseline at Study Week 26 ...

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. 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 ...

7. 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 ...

8. 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 ...