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

Overview[ - collapse ][ - ]

Purpose The purpose of the study is to assess the safety of the addition of sitagliptin, and its effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this study is that sitagliptin reduces A1C more than placebo after 20 weeks of treatment.
ConditionDiabetes Mellitus
Type 2 Diabetes
InterventionDrug: Sitagliptin
Drug: Metformin
Drug: Placebo to sitagliptin
Drug: Placebo to metformin
Drug: Metformin Rescue
Drug: Sitagliptin Rescue
Biological: Insulin Rescue
PhasePhase 3
SponsorMerck Sharp & Dohme Corp.
Responsible PartyMerck Sharp & Dohme Corp.
ClinicalTrials.gov IdentifierNCT01485614
First ReceivedDecember 1, 2011
Last UpdatedApril 17, 2014
Last verifiedApril 2014

Tracking Information[ + expand ][ + ]

First Received DateDecember 1, 2011
Last Updated DateApril 17, 2014
Start DateFebruary 2012
Estimated Primary Completion DateNovember 2017
Current Primary Outcome Measures
  • Change from baseline in A1C [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Number of participants with adverse events (AE) [Time Frame: Up to 56 weeks] [Designated as safety issue: Yes]
  • Number of participants who discontinued study medication due to an AE [Time Frame: Up to 54 weeks] [Designated as safety issue: Yes]
Current Secondary Outcome Measures
  • Change from baseline in A1C at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Percentage of participants with an A1C target of <7.0%, <6.5% at Week 20 [Time Frame: Week 20] [Designated as safety issue: No]
  • Percentage of participants with an A1C target of <7.0%, <6.5% at Week 54 [Time Frame: Week 54] [Designated as safety issue: No]
  • Change from baseline in fasting plasma glucose (FPG) at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in FPG at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Change from baseline in insulin at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in insulin at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Change from baseline in proinsulin at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in proinsulin at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Change from baseline in proinsulin/insulin ratio at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in proinsulin/insulin ratio at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Change from baseline in Homeostatic Model Assessment of β-cell function (HOMA-β) at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in HOMA-β at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Change from baseline in Homeostatic Model Assessment of insulin resistance (HOMA-IR) at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in HOMA-IR at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Change from baseline in endpoints at 2 hours after the start of the meal for 2-hour PMG and 2-hour incremental PMG at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in endpoints at 2 hours after the start of the meal for 2-hour PMG and 2-hour incremental PMG at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Change from baseline in AUC endpoints (Total AUC and Excursion AUC) for glucose, insulin, C-peptide, proinsulin, proinsulin AUC/Insulin AUC, Insulin AUC/ Glucose AUC at Week 20 [Time Frame: Baseline and Week 20] [Designated as safety issue: No]
  • Change from baseline in AUC endpoints (Total AUC and Excursion AUC) for glucose, insulin, C-peptide, proinsulin, proinsulin AUC/Insulin AUC, Insulin AUC/ Glucose AUC at Week 54 [Time Frame: Baseline and Week 54] [Designated as safety issue: No]
  • Proportion of patients requiring glycemic rescue therapy at Week 20 [Time Frame: Week 20] [Designated as safety issue: No]
  • Proportion of patients requiring glycemic rescue therapy at Week 54 [Time Frame: Week 54] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleStudy to Assess Safety & Efficacy of Sitagliptin as Initial Monotherapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants (MK-0431-083)
Official TitleA 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
Brief Summary
The purpose of the study is to assess the safety of the addition of sitagliptin, and its
effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2
diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this
study is that sitagliptin reduces A1C more than placebo after 20 weeks of treatment.
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).

Two arms of the study were removed from the study by a protocol amendment.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Condition
  • Diabetes Mellitus
  • Type 2 Diabetes
InterventionDrug: Sitagliptin
100 mg oral tablet of sitagliptin prior to the morning meal in Phase A and Phase B.
Other Names:
JanuviaDrug: Metformin
Metformin (500 mg), 2 tablets twice daily prior to morning and evening meals
Other Names:
GlucophageDrug: Placebo to sitagliptin
After randomization: Participants randomized to the Placebo Phase A/Metformin Phase B arm will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. Phase B: Participants in the Placebo Phase A/Metformin Phase B arm will continue to receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. For 1 week, participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.
Drug: Placebo to metformin
After randomization: Participants randomized to the Sitagliptin Arm and those randomized to the Placebo Phase A/Metformin Phase B arm will receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. Phase B: Participants in the Sitagliptin Arm will continue to receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. For 1 week participants will receive oral tablets of placebo to metformin (500 mg), 2 tablets prior to the morning and evening meals.
Drug: Metformin Rescue
Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 1 (blinded), eligible participants receiving sitagliptin or placebo (in Phase A), or sitagliptin (in Phase B) will initiate metformin.
Drug: Sitagliptin Rescue
Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 1 (blinded), eligible participants receiving metformin (in Phase B) will initiate sitagliptin.
Biological: Insulin Rescue
Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 2 (open-label), participants receiving sitagliptin, placebo or metformin will receive insulin according to routine clinical practice.
Study Arm (s)
  • Experimental: Sitagliptin
    Sitagliptin 100 mg oral tablet once a day and placebo to metformin oral tablet (500 mg), 2 tablets twice daily prior to morning and evening meals for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will continue to receive Phase A treatment during Phase B (34 weeks).
  • Active Comparator: Metformin
    Metformin (500 mg) oral tablets, 2 tablets twice daily prior to morning and evening meals and placebo to sitagliptin (100 mg), oral tablet once daily for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will continue to receive Phase A treatment for 34 weeks (Phase B). This arm of the study was removed by a protocol amendment.
  • Experimental: Placebo Phase A/Sitagliptin B
    Placebo to sitagliptin oral tablet once a day and placebo to metformin oral tablets (500 mg), 2 tablets twice daily prior to morning and evening meals for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will receive 1 tablet of sitagliptin daily and 2 tablets of metformin placebo twice daily prior to morning and evening meals (Phase B). This arm of the study was removed by a protocol amendment.
  • Experimental: Placebo Phase A / Metformin Phase B
    Placebo to sitagliptin oral tablet once a day and placebo to metformin oral tablets (500 mg), 2 tablets twice daily prior to morning and evening meals for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will receive 1 tablet of sitagliptin-placebo daily and metformin oral tablets (500 mg), 2 tablets twice daily prior to morning and evening meals during Phase B (34 weeks).

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment170
Estimated Completion DateNovember 2017
Estimated Primary Completion DateNovember 2017
Eligibility Criteria
Inclusion Criteria:

- Type 2 Diabetes Mellitus (T2DM)

- Has not received treatment with an oral antihyperglycemic agent (AHA) or insulin for
≥12 weeks prior to the Screening Visit/Visit 1.

- An A1C of ≥6.5% and ≤10.0%.

Exclusion Criteria:

- 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 (Glucagon-like peptide-1) GLP-1 receptor
agonist (such as exenatide or liraglutide).

- Hypersensitivity or contraindication (according to the product circular in the
country of the investigational site) to metformin.

- Chronic treatment with a medication known to cause weight gain within 30 days of
study start or weight loss or increased blood glucose within 8 weeks of study start
or treated with an anti-psychotic within the past 12 weeks.

- On a weight loss program and not in the maintenance phase or have undergone bariatric
surgery within 12 months prior to study start.

- On or likely to require treatment with ≥14 consecutive days or repeated courses of
pharmacologic doses of corticosteroids.

- Undergone a surgical procedure within the prior 4 weeks or has major surgery planned
during the study.

- History of congenital heart disease or cardiovascular disease other than
hypertension.

- Medical history of active liver disease (other than non-alcoholic hepatic steatosis),
including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic
gallbladder disease.

- Active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).

- Chronic myopathy, mitochondrial disorder, or a progressive neurological or
neuromuscular disorder (e.g., polymyositis, or multiple sclerosis).

- Human immunodeficiency virus (HIV) as assessed by medical history.

- Clinically significant hematological disorder (such as aplastic anemia,
thrombocytopenia, myeloproliferative or myelodysplastic syndrome).

- 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.

- History of idiopathic acute pancreatitis or chronic pancreatitis.
GenderBoth
Ages10 Years
Accepts Healthy VolunteersNo
ContactsContact: Toll Free Number
1-888-577-8839
Location CountriesUnited States, Argentina, Australia, Austria, Bulgaria, Canada, Chile, Colombia, Denmark, Dominican Republic, Germany, Guatemala, Hungary, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, New Zealand, Panama, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Thailand

Administrative Information[ + expand ][ + ]

NCT Number NCT01485614
Other Study ID Numbers0431-083
Has Data Monitoring CommitteeYes
Information Provided ByMerck Sharp & Dohme Corp.
Study SponsorMerck Sharp & Dohme Corp.
CollaboratorsNot Provided
Investigators Study Director: Medical Director Merck Sharp & Dohme Corp.
Verification DateApril 2014

Locations[ + expand ][ + ]

Call for Information (Investigative Site 0312)
Birmingham, Alabama, United States, 35233-1711
Recruiting
Call for Information (Investigational Site 0312)
Birmingham, Alabama, United States, 35233-1711
Recruiting
Call for Information (Investigational Site 0316)
Phoenix, Arizona, United States, 85048
Recruiting
Call for Information (Investigational Site 0317)
Phoenix, Arizona, United States, 85016
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Call for Information (Investigational Site 0012)
Canoga Park, California, United States, 91303
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Call for Information (Investigational Site 0013)
Clovis, California, United States, 93612
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Call for Information (Investigational Site 0018)
Los Angeles, California, United States, 90048
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Call for Information (Investigational Site 0020)
Sacramento, California, United States, 95821
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Call for Information (Investigational Site 0019)
San Diego, California, United States, 92123
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Call for Information (Investigational Site 0334)
San Diego, California, United States, 92102
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Call for Information (Investigational Site 0307)
Ventura, California, United States, 93003
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Call for Information (Investigational Site 0023)
Aurora, Colorado, United States, 80045
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Call for Information (Investigational Site 0325)
Atlanta, Georgia, United States, 30342
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Call for Information (Investigational Site 0326)
Thomaston, Georgia, United States, 30286
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Call for Information (Investigational Site 0303)
Louisville, Kentucky, United States, 40202
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Call for Information (Investigational Site 0009)
Portland, Maine, United States, 04102
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Call for Information (Investigational Site 0305)
Baltimore, Maryland, United States, 21215
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Call for Information (Investigational Site 0309)
Neptune, New Jersey, United States, 07753
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Call for Information (Investigational Site 0310)
Lake Success, New York, United States, 11042
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Call for Information (Investigational Site 0011)
Rochester, New York, United States, 14642
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Call for Information (Investigational Site 0014)
Akron, Ohio, United States, 44308
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Call for Information (Investigational Site 0090)
Canal Fulton, Ohio, United States, 44614
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Call for Information (Investigational Site 0096)
Toledo, Ohio, United States, 43606
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Call for Information (Investigational Site 0324)
Lebanon, Tennessee, United States, 37087
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Call for Information (Investigational Site 0015)
Boerne, Texas, United States, 78006
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Call for Information (Investigational Site 0322)
Edinburg, Texas, United States, 78539
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Call for Information (Investigational Site 0017)
Houston, Texas, United States, 77081
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Call for Information (Investigational Site 0006)
San Antonio, Texas, United States, 78229
Recruiting
Merck Sharp & Dohme (Argentina) Inc.
Buenos Aires, Argentina
Contact: Alfredo Wilkinson | 54 11 4796 8200
Recruiting
Merck Sharp & Dohme
North Ryde, Australia
Contact: Gary Jankelowitz | 61 2 8988 8246
Recruiting
MSD ýterreich GmbH
Vienna, Austria
Contact: Karl Boegl | 43 126044130
Recruiting
Merck Sharp & Dohme Bulgaria EOOD
Sofia, Bulgaria
Contact: Eran Gefen | 38 (044) 393 74 80
Recruiting
Merck Canada
Kirkland, Quebec, Canada, H9H 3L1
Contact: Medical Information Centre / Centre de l'information medicale de Merck Canada | 514-428-8600 / 1-800-567-2594
Recruiting
Merck Sharp & Dohme (I.A.) Corp.
Santiago, Chile
Contact: Maria Elena Azara Hernandez | 56 2 6558958
Recruiting
MDS Colombia SAS
Bogota, Colombia
Contact: Francesca Carvajal | 57 1219109011090
Recruiting
Merck Sharp & Dohme
Glostrup, Denmark
Contact: Gert Andersen | 45 44824475
Recruiting
Merck Sharp & Dohme
Santo Domingo, Dominican Republic
Contact: Felipe Arbelaez | (787) 474-8200
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Merck Sharp & Dohme GmbH
Haar, Germany
Contact: German Medical Information Center | 49 800 673 673 673
Recruiting
MSD CARD
Guatemala, Guatemala
Contact: Soraya Cedraro | 507-282-7200
Recruiting
MSD Pharma Hungary Kft.
Budapest, Hungary
Contact: Simona Martinkova | 36 1 457 8522
Recruiting
Merck Sharp & Dohme Co. Ltd.
Hod Hasharon, Israel
Contact: Ofer Sharon | 972 9 9539310
Recruiting
MSD Italia S.r.l.
Rome, Italy
Contact: Patrizia Nardini | 39 06 361911
Recruiting
Merck Sharp & Dohme Latvija SIA
Riga, Latvia
Contact: Andrius Bacevicius | 370 52780243
Recruiting
UAB "Merck Sharp & Dohme"
Vilnius, Lithuania
Contact: Andrius Bacevicius | 370 52780243
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MSD
Petaling Jaya, Malaysia
Contact: Boon Hock Yeoh | 60 377181723
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MSD
Mexico City, Mexico
Contact: Juan Marques | 52 55254819608
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Merck Sharp & Dohme (New Zealand) Ltd.,
Wellington, New Zealand
Contact: Gary Jankelowitz | 61 2 8988 8246
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MSD CARD
Panama, Panama
Contact: Soraya Cedraro | 507-282-7200
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MSD Polska Sp. Z o.o.
Warsaw, Poland
Contact: Adam Czernik | 48 22 4784324
Recruiting
Merck Sharp & Dohme Romania SRL
Bucharest, Romania
Contact: Eran Gefen | 38 (044) 393 74 80
Recruiting
Merck Sharp & Dohme IDEA, Inc.
Moscow, Russian Federation
Contact: Maria Koroleva | 7 0959410000
Recruiting
Merck Sharp Dohme S.R.O.
Bratislava, Slovakia
Contact: Eva Kaszasova | 420 233010213
Recruiting
Merck Sharp and Dohme de Espana S.A.
Madrid, Spain
Contact: Cesar Sanz Rodriguez | 34 913210600
Recruiting
MSD
Sollentuna, Sweden
Contact: Tryggve Ljung | 46 (0)70 545 28 66
Recruiting
MSD (Thailand) Ltd.
Bangkok, Thailand
Contact: Thanu Komolsai | 66 2262 5746
Recruiting