A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Study to Evaluate the Safety and Efficacy of Ertugliflozin (MK-8835/PF-04971729) in Pediatric Participants (ages 10 to 17 years, inclusive) with Type 2 Diabetes Mellitus (MK-8835-059/B1521066)

The primary objective of this clinical study is to evaluate the efficacy of adding **ertugliflozin** compared to placebo in altering hemoglobin A1C (A1C) levels from baseline at 24 weeks in pediatric participants with **Type 2 Diabetes Mellitus**. This is clinically relevant as it aims to determine the potential of ertugliflozin in managing blood glucose levels in a younger population, which could lead to improved long-term outcomes in managing this chronic condition. Additionally, the study seeks to assess the safety and tolerability of ertugliflozin over periods of 24 and 54 weeks, which is crucial for understanding the risk-benefit profile of the medication in this demographic.

Secondary objectives include: - Comparing the addition of ertugliflozin, with dosing optimized according to A1C response, to placebo on the change from baseline in A1C at 24 weeks. - Comparing the addition of ertugliflozin 5 mg to placebo on the change from baseline in A1C at 24 weeks. - Evaluating the effect of adding ertugliflozin versus placebo on the change from baseline in fasting plasma glucose (FPG) at 24 weeks. - Assessing within-group changes from baseline at 54 weeks for A1C and FPG in both the ertugliflozin and placebo groups.

The clinical trial involves a total of **130 participants** diagnosed with **Type 2 Diabetes Mellitus**. The study population includes both male and female subjects, with an age range that encompasses adults. Participants were selected based on specific criteria, including a diagnosis of diabetes according to the American Diabetes Association criteria and a body mass index (BMI) at or above the 85th percentile at screening, or a history of being overweight or obese at the time of diagnosis. The trial includes individuals who have had Type 2 Diabetes Mellitus for at least two years or less than two years with a fasting C-peptide value greater than 0.6 ng/mL at screening. All participants are required to be on stable metformin monotherapy or a stable dose of insulin for at least eight weeks prior to screening. The trial population also includes a vulnerable population, and participants are expected to have a family member or adult closely involved in their daily activities and treatment. Both male and female participants are required to adhere to local regulations regarding contraception. The study does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the safety and efficacy of **ertugliflozin** in pediatric participants aged 10 to 17 years with **Type 2 Diabetes Mellitus**. The trial aims to compare the addition of ertugliflozin with placebo on the change from baseline in hemoglobin A1C (HbA1C) at 24 weeks, and to assess the safety and tolerability of ertugliflozin over 24 and 54 weeks. The study is expected to conclude by September 2025, with recruitment having started in October 2019.

Participants will be involved in the study for a maximum of 54 weeks. The trial includes several key visits: an initial screening visit to confirm eligibility based on criteria such as a diagnosis of diabetes by ADA standards, a body mass index at or above the 85th percentile, and stable metformin monotherapy. Following the screening, participants will be randomized to receive either ertugliflozin or placebo. Study visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The primary endpoint is the change in HbA1C at 24 weeks, with secondary endpoints including changes in fasting plasma glucose and HbA1C at 54 weeks.

Participants may be withdrawn from the study if they experience adverse events that necessitate discontinuation of the study treatment, or if they fail to adhere to the study protocol. The trial is not categorized as low intervention and is conducted under Phase III, aiming to confirm the safety and efficacy of ertugliflozin in the target population. The study involves the administration of the investigational product in the form of film-coated tablets, taken orally, with a maximum daily dose of 15 mg and a total treatment period of up to 42 days for each cycle.

The clinical trial involves the administration of **ertugliflozin**, a film-coated tablet, as the experimental medication. Ertugliflozin is chemically derived and is provided in two dosages: 5 mg and 15 mg. The tablets are administered orally. The maximum daily dose is 15 mg, with a total maximum dose of 4410 mg over a treatment period of 42 days. The active substance in ertugliflozin is also known by the synonym PF-04971729. The pharmaceutical form is a film-coated tablet, and the product is manufactured by Merck & Co. Inc. Participant compliance with the dosing schedule is monitored throughout the trial.

The study also includes a **placebo** group to serve as a comparator treatment. The placebo is designed to mimic the appearance of the ertugliflozin film-coated tablets and is available in two forms corresponding to the 5 mg and 15 mg dosages of the active drug. The placebo tablets are administered orally, following the same dosing schedule as the active treatment group. The use of placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thus maintaining the integrity of the trial results.

The efficacy of **ertugliflozin** in pediatric participants with Type 2 Diabetes Mellitus will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the change from baseline in Hemoglobin A1C (HbA1C) at 24 weeks, comparing pooled doses of ertugliflozin (5 mg and 15 mg) versus placebo. Secondary endpoints include changes from baseline in HbA1C at Week 24 for dose-optimized ertugliflozin versus placebo, changes in HbA1C at Week 24 for ertugliflozin 5 mg versus placebo, changes in Fasting Plasma Glucose (FPG) at 24 weeks, and changes in both HbA1C and FPG at 54 weeks.

These efficacy parameters will be measured at specified timepoints, including 24 weeks and 54 weeks, using validated laboratory tests to ensure accuracy and reliability. The data collected will be analyzed to determine the efficacy of ertugliflozin in improving glycemic control in the target population. The study is designed as a Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial, ensuring rigorous assessment of the drug's efficacy and safety profile.