Ertugliflozin Type 2 Diabetes Mellitus (T2DM) Pediatric Study (MK-8835/PF-04971729) (MK-8835-059)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Ertugliflozin 15 mg; Drug: Ertugliflozin 5 mg; Biological: Insulin; Drug: Placebo to ertugliflozin 5 mg; Drug: Metformin; Drug: Placebo to ertugliflozin 15 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04029480

PHRR190913-002184 (Registry Identifier)

U1111-1279-3984 (Registry Identifier)

MK-8835-059 (Other Identifier)

2017-003455-35 (EudraCT Number)

8835-059

2022-501085-21-00 (Registry Identifier)

Details and patient eligibility

About

This study evaluated the safety and efficacy of ertugliflozin (MK-8835) in pediatric participants with T2DM on metformin with/without insulin. The primary hypothesis of the study was that the addition of ertugliflozin reduces hemoglobin A1C (HbA1C) more than the addition of placebo after 24 weeks of treatment.

Full description

Participants were randomized on Day 1 to the following arms:

• 5 mg ERTU and placebo to 15 mg ERTU (5 mg Ertugliflozin)
• placebo to 5 mg ERTU and placebo to 15 mg ERTU (Placebo)

At Week 12, participants who met the up-titration criteria were re-randomized to the following arms for Weeks 12 to 54:

• 5 mg ERTU and placebo to 15 mg ERTU (5 mg/5 mg Ertugliflozin)
• 15 mg ERTU and placebo to 5 mg ERTU (5 mg/15 mg Ertugliflozin) Participants who did not meet the up-titration criteria remained on 5 mg ERTU and placebo to 15 mg ERTU from Week 12 to Week 54.

The placebo arm continued receiving placebo from Week 12 to Week 54.

Enrollment: 166 patients

Sex: All

Ages: 10 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

• Be ≥10 years and ≤17 years of age, when the informed consent is signed
• Has diabetes diagnosed by one of the American Diabetes Association (ADA) criteria.
• Has body mass index (BMI) ≥85th percentile at screening OR participant has a history of being overweight or obese at time of diagnosis of Type 2 diabetes mellitus (T2DM).
• T2DM for ≥2 years, OR T2DM for <2 years and a fasting C-peptide value >0.6 ng/mL at Screening.
• On stable metformin monotherapy (≥1500 mg/day, for ≥8 weeks prior to Screening, OR on a stable metformin dose (≥1500 mg/day, for ≥8 weeks prior to Screening and a stable dose of insulin for ≥8 weeks prior to Screening.
• Contraceptive use by male participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Is a non-sterilized female who is currently not sexually active OR who agrees to abstain from heterosexual activity OR who agrees to start contraception prior to initiating sexual activity and who agrees to use an adequate method of contraception. Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Have a family member or adult who, along with the participant, will be closely involved in the participant's daily activities (in the opinion of the investigator) and in the participant's treatment and study procedures.

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

• Has known type 1 diabetes mellitus or documented evidence of positive diabetes autoantibodies performed when participant was diagnosed with diabetes.
• Has known monogenic diabetes, or secondary diabetes.
• Has symptomatic hyperglycemia and/or moderate to large ketonuria requiring immediate initiation of another antihyperglycemic agent, including insulin.
• Has a known hypersensitivity or intolerance to any sodium glucose co-transporter 2 (SGLT2) inhibitor.
• Is pregnant, or breast feeding or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study medication.
• Has previously taken an SGLT2 inhibitor (such as canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin) or was enrolled in a study for these agents.
• Has a history of idiopathic acute pancreatitis or chronic pancreatitis.
• Has a history of severe hypoglycemia while on insulin.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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166 participants in 4 patient groups, including a placebo group

Ertugliflozin 5 mg

Experimental group

Description:

All participants initially received 5 mg ertugliflozin (ERTU) once daily (QD) and placebo to 15 mg ERTU QD until Week 54 (WK54). At Week 12 (WK12), participants who did not meet the up-titration criteria remained on 5 mg ERTU and placebo to 15 mg ERTU. Participants remained on their background metformin with/without insulin treatment throughout the study.

Treatment:

Drug: Placebo to ertugliflozin 15 mg

Drug: Metformin

Biological: Insulin

Drug: Ertugliflozin 5 mg

Ertugliflozin 5 mg/5 mg

Experimental group

Description:

All participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until Week 12. Participants remained on their background metformin with/without insulin treatment throughout the study. Participants who met the up-titration criteria at the WK12 second randomization were re-randomized to remain on 5 mg ERTU and placebo to 15 mg ERTU from WK12 to WK54.

Treatment:

Drug: Placebo to ertugliflozin 15 mg

Drug: Metformin

Biological: Insulin

Drug: Ertugliflozin 5 mg

Ertugliflozin 5 mg/15 mg

Experimental group

Description:

All participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until Week 12. Participants remained on their background metformin with/without insulin treatment throughout the study. Participants who met the up-titration criteria at the WK12 second randomization were up-titrated to 15 mg ERTU and placebo to 5 mg ERTU from WK12 to WK54.

Treatment:

Drug: Placebo to ertugliflozin 15 mg

Drug: Metformin

Biological: Insulin

Drug: Placebo to ertugliflozin 5 mg

Drug: Ertugliflozin 5 mg

Drug: Ertugliflozin 15 mg

Placebo

Placebo Comparator group

Description:

All participants received matched placebo to 5 mg ERTU and 15 mg ERTU from baseline to WK54. Participants remained on their background metformin with/without insulin treatment throughout the study.

Treatment:

Drug: Placebo to ertugliflozin 15 mg

Drug: Metformin

Biological: Insulin

Drug: Placebo to ertugliflozin 5 mg