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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01760447




Registration number
NCT01760447
Ethics application status
Date submitted
2/01/2013
Date registered
4/01/2013
Date last updated
23/09/2022

Titles & IDs
Public title
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)
Scientific title
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)
Secondary ID [1] 0 0
2012-004035-23
Secondary ID [2] 0 0
0431A-289
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sitagliptin plus metformin
Treatment: Drugs - Placebo to metformin
Treatment: Drugs - Metformin
Treatment: Drugs - Placebo to sitagliptin plus metformin
Treatment: Drugs - Sitagliptin plus metformin XR
Treatment: Drugs - Placebo to metformin XR
Treatment: Drugs - Insulin
Treatment: Drugs - Placebo to sitagliptin plus metformin XR
Treatment: Drugs - Metformin XR

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.

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.

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.

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.


Treatment: Drugs: Sitagliptin plus metformin
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.

Treatment: Drugs: Placebo to metformin
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.

Treatment: Drugs: Metformin
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.

Treatment: Drugs: Placebo to sitagliptin plus metformin
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.

Treatment: Drugs: Sitagliptin plus metformin XR
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.

Treatment: Drugs: Placebo to metformin XR
Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.

Treatment: Drugs: Insulin
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.

Treatment: Drugs: Placebo to sitagliptin plus metformin XR
Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.

Treatment: Drugs: Metformin XR
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in A1C at Week 20
Timepoint [1] 0 0
Baseline and Week 20
Primary outcome [2] 0 0
Number of Participants Who Experienced =1 Adverse Event During Weeks 0-20
Timepoint [2] 0 0
Up to Week 20
Primary outcome [3] 0 0
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20
Timepoint [3] 0 0
Up to Week 20
Primary outcome [4] 0 0
Number of Participants Who Experienced =1 Adverse Event During Weeks 0-56
Timepoint [4] 0 0
Up to approximately Week 56
Primary outcome [5] 0 0
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54
Timepoint [5] 0 0
Up to Week 54
Secondary outcome [1] 0 0
Change From Baseline in A1C at Week 54
Timepoint [1] 0 0
Baseline and Week 54
Secondary outcome [2] 0 0
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Timepoint [2] 0 0
Baseline and Week 20
Secondary outcome [3] 0 0
Change From Baseline in FPG at Week 54
Timepoint [3] 0 0
Baseline and Week 54
Secondary outcome [4] 0 0
Percentage of Participants With A1C at Goal (<7.0%) at Week 20
Timepoint [4] 0 0
Week 20
Secondary outcome [5] 0 0
Percentage of Participants With A1C at Goal (<6.5%) at Week 20
Timepoint [5] 0 0
Week 20
Secondary outcome [6] 0 0
Percentage of Participants With A1C at Goal (<7.0%) at Week 54
Timepoint [6] 0 0
Week 54
Secondary outcome [7] 0 0
Percentage of Participants With A1C at Goal (<6.5%) at Week 54
Timepoint [7] 0 0
Week 54
Secondary outcome [8] 0 0
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
Timepoint [8] 0 0
Up to Week 20
Secondary outcome [9] 0 0
Percentage of Participants Initiating Insulin Glargine During Weeks 20-54
Timepoint [9] 0 0
Week 20 up to Week 54

Eligibility
Key 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
Minimum age
10 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/09/2019
Sample size
Target
Accrual to date
Final
223
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01760447
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01760447