A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin) (MK-0431A-170/MK-0431A-289)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Sitagliptin plus metformin XR; Drug: Placebo to metformin; Drug: Placebo to sitagliptin plus metformin; Drug: Sitagliptin plus metformin; Drug: Metformin; Drug: Insulin; Drug: Metformin XR; Drug: Placebo to sitagliptin plus metformin XR; Drug: Placebo to metformin XR

Study type: Interventional

Funder types: Industry

Identifiers

NCT01760447

2014-003583-20 (EudraCT Number)

2011-002529-23 (EudraCT Number)

2012-004035-23 (EudraCT Number)

0431A-289

CTRI/2012/09/003025 (Registry Identifier)

MK-0431A-170 (Other Identifier)

MK-0431A-289 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to assess the effect of the addition of sitagliptin (administered as MK-0431A or MK-0431A XR) relative to the addition of placebo on glycated hemoglobin (A1C), and the safety and tolerability of the addition of sitagliptin, in pediatric participants (ages 10-17 years) with type 2 diabetes mellitus with inadequate glycemic control on metformin therapy (alone or in combination with insulin). The primary hypothesis is that the addition of sitagliptin reduces glycated hemoglobin (A1C) more than the addition of placebo after 20 weeks of treatment.

Enrollment: 223 patients

Sex: All

Ages: 10 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• For MK-0431A-170 base study and MK-0431A-289:

  • Has type 2 diabetes mellitus (T2DM)
  • Is on metformin monotherapy (≥1500 mg/day) for ≥12 weeks with glycated hemoglobin (A1C) ≥6.5% and ≤10.0% OR is on stable doses of metformin (≥1500 mg/day) and insulin for ≥12 weeks with an A1C ≥7.0% and ≤10%. NOTE: Participants on a daily dose of metformin greater than or equal to 1000 mg/day, but less than 1500 mg/day may be eligible if there is documentation that higher doses are not tolerated.
  • Participant and a family member or adult closely involved in the daily activities will participate in the participant's treatment and study protocol (i.e., available for telephone calls, study visits and administration of study medication as needed).
  • Male, or female who is unlikely to conceive (non-sterilized, and is not sexually active or agrees to abstain from heterosexual activity or agrees to use an adequate method of contraception) during the study and for 14 days after the last dose of study drug

• For MK-0431A-170 extension protocol:

  • Has completed the P170 base study
  • Participant and a family member or adult closely involved in the daily activities will participate in the participant's treatment and study protocol (i.e., available for telephone calls, study visits and administration of study medication as needed).
  • Male, or female who is unlikely to conceive (non-sterilized, and is not sexually active or agrees to abstain from heterosexual activity or agrees to use an adequate method of contraception) during the study and for 14 days after the last dose of study drug

Exclusion criteria

• For MK-0431A-170 base study and MK-0431A-289:

  • Has type 1 diabetes mellitus
  • Has monogenic diabetes or secondary diabetes
  • Has symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive test for ketonemia, requiring immediate initiation of another antihyperglycemic agent
  • Has previously taken a dipeptidyl peptidase IV (DPP-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, saxagliptin, or linagliptin) or glucagon-like peptide-1 (GLP-1) receptor agonist (such as exenatide or liraglutide)
  • Is on or likely to require treatment for ≥2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
  • Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study
  • History of congenital heart disease or cardiovascular disease other than hypertension
  • History of active liver disease (other than non-alcoholic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
  • Active neuropathy (such as nephrotic syndrome or glomerulonephritis)
  • Chronic myopathy, mitochondrial disorder or a progressive neurological or neuromuscular disorder
  • Human immunodeficiency virus (HIV)
  • Hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndromes)
  • Is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
  • History of malignancy for ≤5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
  • History of idiopathic acute pancreatitis or chronic pancreatitis
  • History of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year)
  • Has donated blood products or has had phlebotomy of >10% of estimated total blood volume within 8 weeks of study participation, or intends to donate blood products or receive blood products within the projected duration of the study
  • 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 drug

• For MK-0431A-170 extension protocol:

  • Participant meets a study medication discontinuation criterion at the last visit of the MK-0431A-170 base study (Week 20)
  • Has taken the last dose of study medication for the MK-0431A-170 base study more than 14 days prior to Extension Visit 1
  • Has initiated another oral antihyperglycemic agent
  • Participant does not agree to refrain from participating in any other double-blind interventional study while participating in the P170 extension study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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223 participants in 4 patient groups, including a placebo group

Sitagliptin/Metformin

Experimental group

Description:

Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170.

Treatment:

Drug: Sitagliptin plus metformin

Drug: Placebo to metformin

Drug: Insulin

Metformin

Placebo Comparator group

Description:

Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170.

Treatment:

Drug: Placebo to sitagliptin plus metformin

Drug: Metformin

Drug: Insulin

Sitagliptin/Metformin XR

Experimental group

Description:

Participants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289.

Treatment:

Drug: Placebo to metformin XR

Drug: Sitagliptin plus metformin XR

Drug: Insulin

Metformin XR

Placebo Comparator group

Description:

Participants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289.

Treatment:

Drug: Placebo to sitagliptin plus metformin XR

Drug: Metformin XR

Drug: Insulin