Diabetes MellitusPhase 3NCT01485614

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

A Phase 3 study testing Sitagliptin, Metformin and Glycemic Rescue 1 in people with Diabetes Mellitus and Type 2 Diabetes, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 10 to 17 years
Conditions the study is for: Diabetes Mellitus, Type 2 Diabetes
What is being tested?: Sitagliptin, Metformin and Glycemic Rescue 1
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 200 participants
Where: No sites listed yet
Study dates: 10 Feb 2012to 9 Oct 2019
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 10 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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%).

Who cannot join

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.

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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).
Under treatment for hyperthyroidism.
Exhibits abnormal growth patterns or is being treated with growth hormone.
History of malignancy or clinically important hematologic disorder.
History of idiopathic acute pancreatitis or chronic pancreatitis.
Known history of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year).
Donated blood products or has had phlebotomy of >10% of estimated total blood volume within 8 weeks of signing informed consent, or intends to donate blood products or receive blood products within the projected duration of the study.
Pregnant, has a positive urine pregnancy test at Screening Visit/Visit 1, is expecting to conceive within the projected duration of the study, or is breast-feeding.
Exclusionary laboratory values.

About this study

Official title: A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control

Read the detailed description

This trial is of approximately 56 weeks in duration, including a screening period of up to 1 week, a 1-week single-blind placebo run-in period, a 20-week placebo-controlled, double blind treatment period [Phase A] and a 34-week double-blind active controlled treatment period [Phase B] during which participants randomized to the placebo arm who have not initiated glycemic rescue therapy with metformin during Phase A will receive metformin (in a blinded manner). A telephone contact will be performed 14 days after the last dose of study medication to assess for any serious adverse events (SAEs).

Participants enrolled in the metformin and placebo/sitagliptin arms prior to implementation of Protocol Amendment 05 completed the study on their original treatment assignments.

EUPASS4468 is a follow-up, non-interventional, observational assessment of safety of participants who participated in the MK-0431-083 study for up to 5 years.

Conditions: Diabetes Mellitus, Type 2 Diabetes
Being tested: Sitagliptin, Metformin, Placebo to sitagliptin, Placebo to metformin, Glycemic Rescue 1
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SitagliptinDrug
Also called Januvia®, Tesavel®, Xelevia®, Ristaben®, Glactiv®
Sitagliptin 100 mg tablet administered orally once daily
MetforminDrug
Also called Glucophage®, Metgluco®, Glycoran®
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
Placebo to sitagliptinDrug
Matching placebo to sitagliptin 100 mg tablet administered orally once daily
Placebo to metforminDrug
Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily
Glycemic Rescue 1Drug
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.
Glycemic Rescue 2Biological
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.

Study groups in NCT01485614
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Sitagliptin; Drug: Placebo to sitagliptin; Drug: Placebo to metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to Week 54

Secondary outcomes (85)

Change From Baseline in A1C at Week 54
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. This change from baseline reflects the Week 54 A1C minus the Week 0 A1C.
Measured: Baseline and Week 54
Percentage of Participants With A1C at Goal (<7.0%) at Week 20
The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
Measured: Week 20
Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
Measured: Week 20
Percentage of Participants With A1C at Goal (<6.5%) at Week 20
The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
Measured: Week 20
Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
Measured: Week 20
Percentage of Participants With A1C at Goal (<7.0%) at Week 54
The percentage of participants with A1C at goal (<7.0%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
Measured: Week 54
Percentage of Participants With A1C at Goal (<6.5%) at Week 54
The percentage of participants with A1C at goal (<6.5%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
Measured: Week 54
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline.
Measured: Baseline and Week 20
Baseline Fasting Plasma Glucose (FPG) for the Placebo (Pooled) Arm
Blood glucose was measured on a fasting basis. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes.
Measured: Baseline
Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline and was estimated from a longitudinal data analysis model. The current outcome measure focused on results from participants randomized to sitagliptin or placebo. The Week 20 treatment comparison of Sitagliptin vs Placebo included all participants treated with Sitagliptin or Placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
Measured: Baseline and Week 20
Change From Baseline in FPG at Week 54
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 54 minus FPG at baseline.
Measured: Baseline and Week 54
Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20
PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour PMG minus the Week 0 2-hour PMG.
Measured: Baseline and Week 20
Change From Baseline in 2-hour PMG at Week 54
PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour PMG minus the Week 0 2-hour PMG.
Measured: Baseline and Week 54
Change From Baseline in 2-hour Incremental PMG at Week 20
2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour incremental PMG minus the Week 0 2-hour incremental PMG.
Measured: Baseline and Week 20
Change From Baseline in 2-Hour Incremental PMG at Week 54
2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour incremental PMG minus the Week 0 2-hour incremental PMG.
Measured: Baseline and Week 54
Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin
This change from baseline reflects the Week 20 insulin minus the Week 0 insulin.
Measured: Baseline and Week 20
Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin
This change from baseline reflects the Week 54 insulin minus the Week 0 insulin.
Measured: Baseline and Week 54
Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin
This change from baseline reflects the Week 20 proinsulin minus the Week 0 proinsulin.
Measured: Baseline and Week 20
Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin
This change from baseline reflects the Week 54 proinsulin minus the Week 0 proinsulin.
Measured: Baseline and Week 54
Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin
Change from baseline was the Week 20 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.
Measured: Baseline and Week 20
Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin
The change from baseline was Week 54 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.
Measured: Baseline and Week 54
Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin
HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. The change from baseline was Week 20 HOMA-β minus the Week 0 HOMA-β.
Measured: Baseline and Week 20
Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin
HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. This change from baseline was Week 54 HOMA-β minus the Week 0 HOMA-β.
Measured: Baseline and Week 54
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin
HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 20 HOMA-IR minus the Week 0 HOMA-IR.
Measured: Baseline and Week 20
Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin
HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 54 HOMA-IR minus the Week 0 HOMA-IR.
Measured: Baseline and Week 54
Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-hour AUC at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-peptide 3-Hour AUC at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin total AUC/glucose total AUC ratio minus the Week 0 insulin total AUC/glucose total AUC ratio.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio.
Measured: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Glucose 3-Hour AUC at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-Hour AUC at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-peptide 3-Hour AUC at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC/glucose 3-hour AUC ratio minus the Week 0 insulin 3-hour AUC/glucose 3-hour AUC ratio.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio.
Measured: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
The percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.
Measured: Up to Week 20
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54
The percentage of participants who initiated glycemic rescue therapy prior to Week 54 was reported.
Measured: Up to Week 54
Change From Baseline in Body Mass Index (BMI) at Week 20
This change from baseline was Week 20 BMI minus the Week 0 BMI.
Measured: Baseline and Week 20
Change From Baseline in BMI at Week 54
This change from baseline was Week 54 BMI minus the Week 0 BMI.
Measured: Baseline and Week 54
Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20
The percent change from baseline in CD26 = ([CD26 value at Week 20] - [baseline CD26 value]) ÷ baseline CD26 value × 100.
Measured: Baseline and Week 20
Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54
The percent change from baseline in CD26 = ([CD26 value at Week 54] - [baseline CD26 value]) ÷ baseline CD26 value × 100.
Measured: Baseline and Week 54
Change From Baseline in Calcitonin at Week 20 - Females
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin.
Measured: Baseline and Week 20
Change From Baseline in Calcitonin at Week 54 - Females
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin.
Measured: Baseline and Week 54
Change From Baseline in Calcitonin at Week 20 - Males
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin.
Measured: Baseline and Week 20
Change From Baseline in Calcitonin at Week 54 - Males
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin.
Measured: Baseline and Week 54
Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents
Measured: Baseline and Week 20
Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents
Measured: Baseline and Week 20
Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. Bone Collagen Equivalents
Measured: Baseline and Week 54
Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. All participants in the Metformin arm were missing baseline or Week 54 measurements. BCE = Bone Collagen Equivalents
Measured: Baseline and Week 54
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
Measured: Baseline and Week 20
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
Measured: Baseline and Week 54
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
Measured: Baseline and Week 20
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
Measured: Baseline and Week 54
Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
Measured: Baseline and Week 20
Percent Change From Baseline in IGF-1 at Week 54 - Females
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
Measured: Baseline and Week 54
Percent Change From Baseline in IGF-1 at Week 20 - Males
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
Measured: Baseline and Week 20
Percent Change From Baseline in IGF-1 at Week 54 - Males
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
Measured: Baseline and Week 54
Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
Measured: Baseline and Week 20
Percent Change From Baseline in IGF-BP3 at Week 54 - Females
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
Measured: Baseline and Week 54
Percent Change From Baseline in IGF-BP3 at Week 20 - Males
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
Measured: Baseline and Week 20
Percent Change From Baseline in IGF-BP3 at Week 54 - Males
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
Measured: Baseline and Week 54
Growth Velocity at Week 20 - Females
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Measured: Week 20
Growth Velocity at Week 54 - Females
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Measured: Week 54
Growth Velocity at Week 20 - Males
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Measured: Week 20
Growth Velocity at Week 54 - Males
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Measured: Week 54
Skeletal Maturation at Week 20 - Females
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from an X-ray of left hand and wrist.
Measured: Week 20
Skeletal Maturation at Week 54 - Females
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Placebo/Sitagliptin arm were missing baseline or Week 54 measurements.
Measured: Week 54
Skeletal Maturation at Week 20 - Males
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist.
Measured: Week 20
Skeletal Maturation at Week 54 - Males
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Metformin and Placebo/Sitagliptin arms were missing baseline or Week 54 measurements.
Measured: Week 54
Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 20 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia.
Measured: Baseline and Week 20
Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 54 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. All participants in the Metformin arm were missing baseline or Week 54 measurements.
Measured: Baseline and Week 54
Change From Baseline in Tanner Staging for Breasts at Week 20 - Females
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 20 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts.
Measured: Baseline and Week 20
Change From Baseline in Tanner Staging for Breasts at Week 54 - Females
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 54 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts.
Measured: Baseline and Week 54
Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
Measured: Baseline and Week 20
Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
Measured: Baseline and Week 54
Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
Measured: Baseline and Week 20
Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
Measured: Baseline and Week 54
Participants With Worsening in Dental Status at Week 20
Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 20 dental assessments versus baseline dental assessments.
Measured: Week 20
Participants With Worsening in Dental Status at Week 54
Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 54 dental assessments versus baseline dental assessments.
Measured: Week 54

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Feb 20129 Oct 2019

First posted5 Dec 2011 (estimated)
Study start10 Feb 2012
Primary completion9 Oct 2019
Study completion9 Oct 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 200 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01485614
Sponsor's protocol ID: 0431-083
Other IDs: 2011-002528-42, MK-0431-083
Status last verified: Sep 2022
First submitted: 1 Dec 2011
Last updated: 23 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 34779087

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)

All Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control
ClinicalTrials.gov ID: NCT01485614
Acronym / sponsor ID: 0431-083
Conditions: Diabetes Mellitus, Type 2 Diabetes
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 200 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 10 Feb 2012 (actual)
Primary completion: 9 Oct 2019 (actual)
Study completion: 9 Oct 2019 (actual)
First posted: 5 Dec 2011 (estimated)
Results: Posted 16 Dec 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Participants enrolled in the metformin and placebo/sitagliptin arms prior to implementation of Protocol Amendment 05 completed the study on their original treatment assignments.

EUPASS4468 is a follow-up, non-interventional, observational assessment of safety of participants who participated in the MK-0431-083 study for up to 5 years.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Sitagliptin	Experimental	Drug: Sitagliptin, Drug: Placebo to metformin, Drug: Glycemic Rescue 1, Biological: Glycemic Rescue 2Participants 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.
Placebo/Metformin	Placebo comparator	Drug: Metformin, Drug: Placebo to sitagliptin, Drug: Placebo to metformin, Drug: Glycemic Rescue 1, Biological: Glycemic Rescue 2Participants 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.
Metformin	Active comparator	Drug: MetforminParticipants 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.
Placebo/Sitagliptin	Placebo comparator	Drug: Sitagliptin, Drug: Placebo to sitagliptin, Drug: Placebo to metforminParticipants 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.

Who may qualify

Ages: 10 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

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%).

Key exclusion criteria (23 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SitagliptinAlso: Januvia®, Tesavel®, Xelevia®, Ristaben®, Glactiv®Sitagliptin 100 mg tablet administered orally once daily	Drug	Placebo/Sitagliptin, Sitagliptin
MetforminAlso: Glucophage®, Metgluco®, Glycoran®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	Drug	Metformin, Placebo/Metformin
Placebo to sitagliptinMatching placebo to sitagliptin 100 mg tablet administered orally once daily	Drug	Placebo/Metformin, Placebo/Sitagliptin
Placebo to metforminMatching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily	Drug	Placebo/Metformin, Placebo/Sitagliptin, Sitagliptin
Glycemic Rescue 1Participants 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.	Drug	Placebo/Metformin, Sitagliptin
Glycemic Rescue 2Participants 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.	Biological	Placebo/Metformin, Sitagliptin

Primary outcome

Change From Baseline in Hemoglobin A1C (A1C) at Week 20
Time frame: Baseline and 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 Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm
Time frame: Baseline
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.
Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
Time frame: Baseline and Week 20
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.
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56
Time frame: Up to Week 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.
Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)
Time frame: Up to Week 56
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.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54
Time frame: Up to Week 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.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)
Time frame: Up to Week 54
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.

85 secondary outcomes

Change From Baseline in A1C at Week 54
Time frame: Baseline and Week 54
Percentage of Participants With A1C at Goal (<7.0%) at Week 20
Time frame: Week 20
Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
Time frame: Week 20
Percentage of Participants With A1C at Goal (<6.5%) at Week 20
Time frame: Week 20
Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
Time frame: Week 20
Percentage of Participants With A1C at Goal (<7.0%) at Week 54
Time frame: Week 54
Percentage of Participants With A1C at Goal (<6.5%) at Week 54
Time frame: Week 54
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Time frame: Baseline and Week 20
Baseline Fasting Plasma Glucose (FPG) for the Placebo (Pooled) Arm
Time frame: Baseline
Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
Time frame: Baseline and Week 20
Change From Baseline in FPG at Week 54
Time frame: Baseline and Week 54
Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20
Time frame: Baseline and Week 20
Change From Baseline in 2-hour PMG at Week 54
Time frame: Baseline and Week 54
Change From Baseline in 2-hour Incremental PMG at Week 20
Time frame: Baseline and Week 20
Change From Baseline in 2-Hour Incremental PMG at Week 54
Time frame: Baseline and Week 54
Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin
Time frame: Baseline and Week 20
Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin
Time frame: Baseline and Week 54
Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin
Time frame: Baseline and Week 20
Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin
Time frame: Baseline and Week 54
Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin
Time frame: Baseline and Week 20
Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin
Time frame: Baseline and Week 54
Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin
Time frame: Baseline and Week 20
Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin
Time frame: Baseline and Week 54
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin
Time frame: Baseline and Week 20
Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin
Time frame: Baseline and Week 54
Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-hour AUC at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-peptide 3-Hour AUC at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20
Time frame: Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Glucose 3-Hour AUC at Week 54
Time frame: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-Hour AUC at Week 54
Time frame: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-peptide 3-Hour AUC at Week 54
Time frame: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54
Time frame: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54
Time frame: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54
Time frame: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54
Time frame: Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)

Results and safety

Results posted to the registry on 16 Dec 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sitagliptin	96	95
Placebo/Metformin	90	90
Metformin	9	9
Placebo/Sitagliptin	5	5

Primary outcome: Change From Baseline in Hemoglobin A1C (A1C) at Week 20

Time frame: Baseline and Week 20. Mean (Standard Deviation). Unit: Percentage

Measure	Sitagliptin n = 78	Placebo/Metformin n = 70	Metformin n = 8	Placebo/Sitagliptin n = 3
Value	-0.13 (1.58)	-0.02 (1.45)	-1.03 (0.72)	0.57 (1.62)

Population analysed: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Primary outcome: Baseline Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm

Time frame: Baseline. Mean (Standard Deviation). Unit: Percentage

Measure	Placebo (Pooled) n = 95
Value	7.58 (1.06)

Population analysed: The analysis population included all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.

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

Time frame: Baseline and Week 20. Least squares mean (95% Confidence Interval). Unit: Percentage

Measure	Sitagliptin n = 95	Placebo (Pooled) n = 95
Value	-0.01 (-0.35 to 0.34)	0.18 (-0.17 to 0.53)

Sitagliptin vs Placebo (Pooled): Least Squares Means Difference: -0.19 (95% CI -0.68 to 0.30), p = 0.448, Mixed Models Analysis

Population analysed: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.

Primary outcome: Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56

Time frame: Up to Week 56. Count of participants. Unit: Participants

Measure	Sitagliptin n = 95	Placebo/Metformin n = 90	Metformin n = 9	Placebo/Sitagliptin n = 5
Value	73	67	7	4

Population analysed: The analysis population includes all randomized participants who received ≥1 dose of study medication.

85 secondary outcomes are reported in the full results.

Adverse events

Time frame: SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sitagliptin	10 of 95 (10.5%)	62 of 95 (65.3%)	1 of 96
Placebo/Metformin	7 of 90 (7.8%)	53 of 90 (58.9%)	0 of 90
Metformin	1 of 9 (11.1%)	7 of 9 (77.8%)	0 of 9
Placebo/Sitagliptin	3 of 5 (60%)	4 of 5 (80%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34779087Shankar 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sitagliptin, Metformin and Glycemic Rescue 1 in people with Diabetes Mellitus and Type 2 Diabetes, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Hemoglobin A1C (A1C) at Week 20 (time frame: Baseline and Week 20). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01485614, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2022.