- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01760447
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)
September 9, 2022 updated by: Merck Sharp & Dohme LLC
A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin)
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.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
223
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
10 years to 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sitagliptin/Metformin
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.
|
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1700 mg or 2000 mg of metformin.
Dosage of metformin was based on each participant's daily metformin dose prior to enrollment.
Other Names:
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal.
Each tablet contained placebo to metformin.
Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.
During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.
|
Placebo Comparator: Metformin
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.
|
Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.
During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 1000 mg, 1700 mg or 2000 mg of metformin.
Dosage was based on each participant's daily metformin dose prior to enrollment.
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal.
Each tablet contained placebo to sitagliptin plus metformin.
Other Names:
|
Experimental: Sitagliptin/Metformin XR
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.
|
Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.
During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.
Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1500 mg or 2000 mg of metformin.
Dosage of metformin XR was based on each participant's daily metformin dose prior to enrollment.
Other Names:
Participants received 2 tablets daily, both taken together with a meal.
Each tablet contained placebo to metformin XR.
|
Placebo Comparator: Metformin XR
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.
|
Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue.
During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.
Participants received 2 tablets daily, both taken together with a meal.
Each tablet contained placebo to sitagliptin plus metformin XR.
Other Names:
Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 1000 mg, 1500 mg or 2000 mg of metformin XR.
Dosage was based on each participant's daily metformin dose prior to enrollment.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in 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.
Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
|
Baseline and Week 20
|
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20
Time Frame: Up to Week 20
|
The number of participants experiencing ≥1 adverse event during Weeks 0-20 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 20
|
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20
Time Frame: Up to Week 20
|
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-20 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 20
|
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56
Time Frame: Up to approximately Week 56
|
The number of participants experiencing ≥1 adverse event during Weeks 0-56 were 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 approximately Week 56
|
Number of Participants Who Discontinued Study Drug Due to Experiencing 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.
|
Up to Week 54
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in A1C at Week 54
Time Frame: Baseline and 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.
Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model.
|
Baseline and Week 54
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Time Frame: Baseline and Week 20
|
Blood glucose was measured on a fasting basis.
Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
|
Baseline and Week 20
|
Change From Baseline in FPG at Week 54
Time Frame: Baseline and Week 54
|
Blood glucose was measured on a fasting basis.
Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model.
|
Baseline and Week 54
|
Percentage of Participants With A1C at Goal (<7.0%) at Week 20
Time Frame: 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.
Percentage of participants with A1C at goal (<7.0%) at Week 20 was presented.
|
Week 20
|
Percentage of Participants With A1C at Goal (<6.5%) at Week 20
Time Frame: 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.
Percentage of participants with A1C at goal (<6.5%) at Week 20 was presented.
|
Week 20
|
Percentage of Participants With A1C at Goal (<7.0%) at Week 54
Time Frame: Week 54
|
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.
Percentage of participants with A1C at goal (<7.0%) at Week 54 was presented.
|
Week 54
|
Percentage of Participants With A1C at Goal (<6.5%) at Week 54
Time Frame: Week 54
|
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.
Percentage of participants with A1C at goal (<6.5%) at Week 54 was presented.
|
Week 54
|
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
Time Frame: Up to Week 20
|
Percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.
|
Up to Week 20
|
Percentage of Participants Initiating Insulin Glargine During Weeks 20-54
Time Frame: Week 20 up to Week 54
|
Percentage of participants who initiated insulin glargine therapy from Weeks 20 through 54 was reported.
|
Week 20 up to Week 54
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Baseline A1C
Time Frame: Baseline
|
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.
|
Baseline
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 7, 2011
Primary Completion (Actual)
September 17, 2019
Study Completion (Actual)
September 17, 2019
Study Registration Dates
First Submitted
January 2, 2013
First Submitted That Met QC Criteria
January 2, 2013
First Posted (Estimate)
January 4, 2013
Study Record Updates
Last Update Posted (Actual)
September 23, 2022
Last Update Submitted That Met QC Criteria
September 9, 2022
Last Verified
September 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Metformin
- Sitagliptin Phosphate
Other Study ID Numbers
- 0431A-289
- 2012-004035-23 (EudraCT Number)
- 2011-002529-23 (EudraCT Number)
- 2014-003583-20 (EudraCT Number)
- MK-0431A-170 (Other Identifier: Merck Protocol Number)
- MK-0431A-289 (Other Identifier: Merck Protocol Number)
- CTRI/2012/09/003025 (Registry Identifier: CTRI)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 2 Diabetes Mellitus
-
SanofiCompletedType 1 Diabetes Mellitus-Type 2 Diabetes MellitusHungary, Russian Federation, Germany, Poland, Japan, United States, Finland
-
Mannkind CorporationTerminatedType 2 Diabetes Mellitus | Type 1 Diabetes MellitusUnited States
-
RWTH Aachen UniversityBoehringer IngelheimCompletedDiabetes Mellitus Type 2 (T2DM)Germany
-
Griffin HospitalCalifornia Walnut CommissionCompletedDIABETES MELLITUS TYPE 2United States
-
Scripps Whittier Diabetes InstituteSan Diego State UniversityCompletedType 2 Diabetes Mellitus (T2DM)United States
-
University Hospital Inselspital, BerneCompletedType 2 Diabetes MellitusSwitzerland
-
India Diabetes Research Foundation & Dr. A. Ramachandran...CompletedTYpe 2 Diabetes MellitusIndia
-
AstraZenecaRecruiting
-
Daewoong Pharmaceutical Co. LTD.Not yet recruitingT2DM (Type 2 Diabetes Mellitus)
-
Zhongda HospitalRecruitingType 2 Diabetes Mellitus (T2DM)China
Clinical Trials on Sitagliptin plus metformin
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompleted
-
Baylor College of MedicineNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)CompletedType 1 DiabetesUnited States
-
Merck Sharp & Dohme LLCCompleted
-
ShionogiCompleted
-
Sihuan Pharmaceutical Holdings Group Ltd.UnknownDiabetes Mellitus, Type 2China
-
Merck Sharp & Dohme LLCCompletedType 2 Diabetes Mellitus
-
Shahid Beheshti University of Medical SciencesRecruitingPolycystic Ovary Syndrome | Infertility | ARTIran, Islamic Republic of
-
Merck Sharp & Dohme LLCCompleted
-
Laboratorios Silanes S.A. de C.V.Completed