J2A-MC-GZGP A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral Orforglipron Compared With Placebo in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-1)

The primary objective of this Phase 3, randomized, double-blind study is to demonstrate that **LY3502970** is superior to placebo in reducing body weight in adult participants with **obesity** or **overweight** with weight-related comorbidities. This objective is clinically relevant as it addresses the need for effective pharmacological interventions in managing obesity, a condition associated with increased morbidity and mortality due to its link with various comorbidities such as cardiovascular diseases, type 2 diabetes, and certain cancers. The study evaluates the efficacy and safety of once-daily oral administration of LY3502970 compared to placebo, providing critical data on its potential as a therapeutic option for weight management in this population.

The clinical trial involves a total of **2484 participants** who are being studied to evaluate the efficacy of LY3502970 in comparison to a placebo for reducing body weight. The study population includes both **male and female** subjects, with an age range that encompasses adults and older adults. Participants are selected based on their status of having **overweight or obesity**, with additional criteria for those who are overweight, such as having high blood pressure, high cholesterol, obstructive sleep apnea, or heart disease. A key lifestyle consideration for inclusion is having at least one self-reported unsuccessful dietary effort to lose weight. The trial includes a vulnerable population, ensuring a comprehensive assessment across different health statuses. The selection process ensures a diverse representation of individuals affected by overweight and obesity, providing valuable insights into the potential benefits of the investigational treatment.

The clinical trial is a **randomized, double-blind, controlled** study designed to evaluate the efficacy and safety of the investigational medicinal product LY3502970, administered orally in capsule form, compared to a placebo in adult participants with **obesity** or **overweight** with weight-related comorbidities. The trial aims to demonstrate that LY3502970 is superior to placebo in reducing body weight. The study is expected to commence recruitment on August 21, 2023, and conclude by July 5, 2027, with a total duration of approximately four years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as having obesity or overweight, and if overweight, the presence of conditions like high blood pressure, high cholesterol, obstructive sleep apnea, or heart disease. Additionally, participants must have a history of unsuccessful dietary efforts to lose weight. Following the screening, eligible participants will be randomized to receive either LY3502970 or placebo. The trial will include multiple follow-up visits to monitor safety, efficacy, and adherence to the treatment regimen. The primary endpoint is the mean percent change from baseline in body weight.

The expected length of participant involvement in the trial is up to one year, with the possibility of early termination if specific conditions arise, such as adverse events or non-compliance with the study protocol. The end-of-study visit will involve a comprehensive assessment to evaluate the overall outcomes and any long-term effects of the treatment. The trial is conducted in accordance with regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of the experimental medication **LY3502970**, which is provided in the form of a capsule. The active substance in LY3502970 is a chemical compound with the complex name 3-((1S,2S)-1-(5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((S)-3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-1H-indol-1-yl)-2-methylcyclopropyl)-5-oxo-1,2,4-oxadiazol-4-ide hemicalcium. The medication is administered orally once daily. The maximum treatment period is set to one day, with no specified maximum daily or total dose amount. The pharmaceutical form is consistent across all experimental products, ensuring uniformity in administration.

In addition to the experimental medication, a **placebo** is utilized in the study to match LY3502970. The placebo is formulated as sodium bicarbonate and is designed to mimic the appearance and administration route of the experimental capsule. The placebo serves as a comparator to evaluate the efficacy and safety of LY3502970 in participants with obesity or overweight conditions accompanied by weight-related comorbidities. The administration of the placebo follows the same oral route and frequency as the experimental medication, ensuring blinding and consistency in the trial design.

The efficacy of the investigational medicinal product LY3502970 will be assessed in a Phase 3, randomized, double-blind clinical trial. The primary endpoint for evaluating efficacy is the **mean percent change from baseline in body weight**. This endpoint will be used to determine the superiority of LY3502970 compared to placebo in adult participants with obesity or overweight with weight-related comorbidities. The trial aims to demonstrate that LY3502970 is more effective than placebo in reducing body weight.