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

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: Type 2 Diabetes Mellitus

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04029480

PHRR190913-002184 (Registry Identifier)

2017-003455-35 (EudraCT Number)

8835-059

2022-501085-21-00 (Registry Identifier)

MK-8859-059 (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 165 estimated patients

Sex: All

Ages: 10 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Has diabetes diagnosed by one of the American Diabetes Association (ADA) criteria.
2. 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).
3. T2DM for ≥2 years, OR T2DM for <2 years and a fasting C-peptide value >0.6 ng/mL at Screening.
4. 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.
5. Contraceptive use by male participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
6. 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.
7. 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

1. Has known type 1 diabetes mellitus or documented evidence of positive diabetes autoantibodies performed when participant was diagnosed with diabetes.
2. Has known monogenic diabetes, or secondary diabetes.
3. Has symptomatic hyperglycemia and/or moderate to large ketonuria requiring immediate initiation of another antihyperglycemic agent, including insulin.
4. Has a known hypersensitivity or intolerance to any sodium glucose co-transporter 2 (SGLT2) inhibitor.
5. 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.
6. Has previously taken an SGLT2 inhibitor (such as canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin) or was enrolled in a study for these agents.
7. Has a history of idiopathic acute pancreatitis or chronic pancreatitis.
8. 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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165 participants in 3 patient groups, including a placebo group

Ertugliflozin 5 mg/5 mg

Experimental group

Description:

All participants will initially receive ertugliflozin (ERTU) 5 mg once daily (QD) and placebo to ERTU 15 mg QD for 12 weeks. At the second randomization at Week 12 (WK12), all participants that do not meet the up-titration criteria will remain on ERTU 5 mg and placebo to ERTU 15 mg from WK12 to WK54. Approximately half the participants who meet the up-titration criteria at the second randomization at WK12 will also remain on ERTU 5 mg and placebo to ERTU 15 mg from WK12 to WK54. Note: For participants not on insulin, the up-titration criterion at the second randomization at WK12 is HbA1C ≥7.0% (53 mmol/mol) and for participants on insulin, a fasting fingerstick glucose (FFSG) of ≥110 mg/dL (6.1 mmol/L) will be required in addition to HbA1C ≥7.0% (53 mmol/mol). Participants will remain on their background metformin with/without insulin treatment throughout the study.

Treatment:

Drug: Placebo to ertugliflozin 15 mg

Drug: Ertugliflozin 5 mg

Drug: Metformin

Biological: Insulin

Ertugliflozin 5 mg/15 mg

Experimental group

Description:

All participants will initially receive ERTU 5 mg QD and placebo to ERTU 15 mg QD for 12 weeks. At the second randomization at WK12, approximately half the participants who meet the up-titration criteria at the second randomization will up-titrate to ERTU 15 mg and placebo to ERTU 5 mg from WK12 to WK54. Note: For participants not on insulin, the up-titration criterion at the second randomization at WK12 is HbA1C ≥7.0% (53 mmol/mol) and for participants on insulin, a FFSG of ≥110 mg/dL (6.1 mmol/L) will be required in addition to HbA1C ≥7.0% (53 mmol/mol). Participants will remain on their background metformin with/without insulin treatment throughout the study.

Treatment:

Drug: Placebo to ertugliflozin 15 mg

Drug: Ertugliflozin 5 mg

Drug: Metformin

Biological: Insulin

Drug: Ertugliflozin 15 mg

Drug: Placebo to ertugliflozin 5 mg

Placebo

Placebo Comparator group

Description:

At the first randomization, participants receive placebo to ERTU 5 mg and placebo to ERTU 15 mg QD for 12 weeks. Participants in the placebo group with HbA1C ≥7.0% (53 mmol/mol) at WK12 will be mock titrated. Note: The up-titration criteria for participants on insulin will include a FFSG of ≥110 mg/dL (6.1 mmol/L) in addition to HbA1C ≥7.0% (53 mmol/mol) at WK12. Participants will continue to receive placebo to ERTU 5 mg and placebo to ERTU 15 mg QD from WK24 to WK54. Participants will remain on their background metformin with/without insulin treatment throughout the study.

Treatment:

Drug: Placebo to ertugliflozin 15 mg

Drug: Placebo to ertugliflozin 5 mg