Study to Assess Safety & Efficacy of Sitagliptin as Initial Oral Therapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants. (MK-0431-083)

NCT01485614 | Completed Phase 3 Results DMC

• 3 other identifiers: 0431-0832011-002528-42MK-0431-083
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to assess the safety of the addition of sitagliptin, and its effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this study is that sitagliptin reduces A1C more than placebo after 20 weeks of treatment.

Conditions

Diabetes Mellitus; Type 2 Diabetes

Outcome Measures

Primary Outcomes (7)

• Change From Baseline in Hemoglobin A1C (A1C) at Week 20

  Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C.

  Baseline and Week 20

• Baseline Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm

  A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes.

  Baseline

• Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))

  Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C from a longitudinal data analysis (LDA) model. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The Statistical Analysis Plan (SAP) did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

  Baseline and Week 20

• Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56

  The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

  Up to Week 56

• Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)

  The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

  Up to Week 56

• Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54

  The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

  Up to Week 54

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)

  The percentage of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.

  Up to Week 54

Secondary Outcomes (85)

• Change From Baseline in A1C at Week 54

  Baseline and Week 54

• Percentage of Participants With A1C at Goal (<7.0%) at Week 20

  Week 20

• Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))

  Week 20

• Percentage of Participants With A1C at Goal (<6.5%) at Week 20

  Week 20

• Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))

  Week 20

Study Arms (4)

Sitagliptin

EXPERIMENTAL

Participants will receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will continue to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.

Drug: Sitagliptin; Drug: Placebo to metformin; Drug: Glycemic Rescue 1; Biological: Glycemic Rescue 2

Placebo/Metformin

PLACEBO COMPARATOR

Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.

Drug: Metformin; Drug: Placebo to sitagliptin; Drug: Placebo to metformin; Drug: Glycemic Rescue 1; Biological: Glycemic Rescue 2

Metformin

ACTIVE COMPARATOR

Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will continue to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.

Drug: Metformin

Placebo/Sitagliptin

PLACEBO COMPARATOR

Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54.

Drug: Sitagliptin; Drug: Placebo to sitagliptin; Drug: Placebo to metformin

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg tablet administered orally once daily

Also known as: Januvia®, Tesavel®, Xelevia®, Ristaben®, Glactiv®

Placebo/Sitagliptin; Sitagliptin

Metformin DRUG

Metformin 500 mg tablets administered orally starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily

Also known as: Glucophage®, Metgluco®, Glycoran®

Metformin; Placebo/Metformin

Placebo to sitagliptin DRUG

Matching placebo to sitagliptin 100 mg tablet administered orally once daily

Placebo/Metformin; Placebo/Sitagliptin

Placebo to metformin DRUG

Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily

Placebo/Metformin; Placebo/Sitagliptin; Sitagliptin

Glycemic Rescue 1 DRUG

Participants in the sitagliptin arm who require glycemic rescue will receive metformin during Weeks 0-20 and Weeks 20-54. Participants in the placebo arm who require glycemic rescue will receive metformin during Weeks 0-20. Participants in the placebo arm who have switched to metformin during Weeks 20-54 and require glycemic rescue will receive sitagliptin.

Placebo/Metformin; Sitagliptin

Glycemic Rescue 2 BIOLOGICAL

Participants who require glycemic rescue after Glycemic Rescue 1 will receive open-label insulin. Participants on background insulin therapy will have the dose of their background insulin up-titrated.

Placebo/Metformin; Sitagliptin

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Type 2 Diabetes Mellitus (T2DM)
• Has not received treatment with an antihyperglycemic agent (AHA) for ≥12 weeks prior to the Screening Visit/Visit 1, or is on a stable dose of insulin (without any other AHA) for at least 12 weeks prior to the Screening Visit/Visit 1. At screening, participants on insulin doses that are not stable can have their insulin doses adjusted and be eligible to participate after their dose remains stable for ≥12 weeks, if they meet all other eligibility criteria. In India, only participants on stable doses of insulin will be eligible.
• An A1C of ≥6.5% and ≤10.0% (For participants on insulin: an A1C ≥7.0% and ≤10.0%).

You may not qualify if:

• History of type 1 diabetes mellitus, autoimmune diabetes mellitus or has a positive antibody screen for anti-GAD (Glutamic Acid Decarboxylase) or (Islet cell autoantigen) ICA-512.
• Known monogenic diabetes, secondary diabetes, or a genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
• Symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive test for ketonemia requiring immediate initiation of antihyperglycemic therapy.
• Previously taken a DPP-4 (Dipeptidyl peptidase-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or GLP-1 (Glucagon-like peptide-1) receptor agonist (such as exenatide or liraglutide).
• Hypersensitivity or contraindication (according to the product circular in the country of the investigational site) to metformin.
• Chronic treatment with a medication known to cause weight gain within 30 days of study start or weight loss or increased blood glucose within 8 weeks of study start or treated with an anti-psychotic within the past 12 weeks.
• On a weight loss program and not in the maintenance phase or have undergone bariatric surgery within 12 months prior to study start.
• On or likely to require treatment with ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.
• Undergone a surgical procedure within the prior 4 weeks or has major surgery planned during the study.
• History of congenital heart disease or cardiovascular disease other than hypertension.
• Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
• Active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).
• Chronic myopathy, mitochondrial disorder, or a progressive neurological or neuromuscular disorder (e.g., polymyositis, or multiple sclerosis).
• Human immunodeficiency virus (HIV) as assessed by medical history.
• Clinically significant hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndrome).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Shankar RR, Zeitler P, Deeb A, Jalaludin MY, Garcia R, Newfield RS, Samoilova Y, Rosario CA, Shehadeh N, Saha CK, Zhang Y, Zilli M, Scherer LW, Lam RLH, Golm GT, Engel SS, Kaufman KD. A randomized clinical trial of the efficacy and safety of sitagliptin as initial oral therapy in youth with type 2 diabetes. Pediatr Diabetes. 2022 Mar;23(2):173-182. doi: 10.1111/pedi.13279. Epub 2021 Dec 22.

  PMID: 34779087 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 5, 2011
• Study Start: February 10, 2012
• Primary Completion: October 9, 2019
• Study Completion: October 9, 2019
• Last Updated: September 23, 2022
• Results First Posted: December 16, 2020

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share