A Randomized, Double-Blind, Placebo-Controlled Trial of Orforglipron (LY3502970) for BMI Reduction in Adolescents with Obesity or Overweight-Related Comorbidities

The primary objective of this clinical trial is to demonstrate that **orforglipron** is superior to placebo in achieving a reduction in **Body Mass Index (BMI)** among pediatric participants with obesity or overweight. This objective is clinically relevant as it addresses the growing concern of obesity in adolescents, which is associated with numerous health risks and comorbidities. Effective weight management in this population can lead to improved health outcomes and reduced risk of developing chronic conditions.

The clinical trial involves a total of **114 participants** diagnosed with **obesity** or **overweight**, each presenting at least one weight-related comorbidity such as abnormal lipids, high blood pressure, fatty liver disease, sleep apnea, prediabetes, or type 2 diabetes. The study population includes both male and female subjects, with an age range that corresponds to adults. Participants were selected based on their inability to lose weight through a healthy diet and physical activity. The trial does not exclude vulnerable populations, indicating a diverse participant group. The primary objective is to assess the efficacy of orforglipron in achieving a reduction in **Body Mass Index (BMI)** compared to a placebo.

The clinical trial is designed to evaluate the **efficacy** and safety of orforglipron, a chemical compound, in adolescent participants diagnosed with **obesity** or overweight with at least one weight-related comorbidity. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thereby minimizing bias. The trial will compare the effects of orforglipron, administered orally in capsule form, against a placebo designed to match LY3502970. The primary objective is to demonstrate that orforglipron is superior to placebo in achieving a reduction in Body Mass Index (BMI) over a period of 72 weeks.

The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria, which require participants to have been diagnosed with obesity or overweight and to have failed to lose weight through diet and physical activity. Following successful screening, participants will be randomized to receive either the investigational product or placebo. The trial will include several follow-up visits to monitor the participants' health, adherence to the treatment regimen, and any adverse events. These visits will also involve assessments of BMI and other relevant health parameters. The end-of-study visit will occur at the conclusion of the 72-week treatment period, where final evaluations will be conducted to assess the primary endpoint of percent change in BMI from baseline.

Participant involvement is expected to last approximately 72 weeks, with the possibility of early termination if significant adverse effects are observed or if the participant withdraws consent. The trial is scheduled to start recruitment in March 2025 and is estimated to conclude by December 2026. The study is categorized as a Phase III trial, focusing on the safety and efficacy of a non-authorized investigational medicinal product. Conditions that may lead to early termination from the study include non-compliance with the study protocol, development of exclusionary medical conditions, or withdrawal of consent by the participant or their legal guardian.

The clinical trial involves the administration of **orforglipron**, a chemical compound with the active substance 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 pharmaceutical form of orforglipron is a capsule, and it is administered orally. The dosing schedule is once daily, with the maximum treatment period being one month. The trial aims to evaluate the efficacy and safety of orforglipron in achieving BMI reduction in pediatric participants with obesity or overweight. The product is manufactured by Eli Lilly and Company Limited and is not a paediatric formulation.

The trial also includes a **placebo** to match LY3502970, which serves as the comparator treatment. The placebo is designed to be indistinguishable from the active treatment in appearance and is administered in the same pharmaceutical form, which is a capsule, and via the same route, orally. The placebo is used to ensure the double-blind nature of the trial, allowing for an unbiased comparison of the effects of orforglipron against no active treatment. The administration schedule for the placebo mirrors that of the active treatment, with a once-daily dosage over a maximum treatment period of one month.

The efficacy of the investigational product, **orforglipron**, will be assessed in a randomized, double-blind clinical trial aimed at demonstrating its superiority over placebo in achieving a reduction in Body Mass Index (BMI) among adolescent participants with obesity or overweight accompanied by weight-related comorbidities. The primary endpoint for evaluating efficacy is the percent change from baseline in BMI, measured at baseline and at Week 72. This endpoint will provide a quantitative assessment of the treatment's impact on BMI over the specified period.