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A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01477853
First received: November 19, 2011
Last updated: November 7, 2014
Last verified: November 2014
  Purpose

This 2 phase study will examine if 16 weeks of treatment with sitagliptin in combination with atorvastatin reduces hemoglobin A1C (A1C) and low density lipoprotein cholesterol (LDL-C) from baseline more than atorvastatin alone and sitagliptin alone, respectively. Following a single-blind placebo run-in period, participants were randomized to one of three treatment arms (sitagliptin monotherapy with placebo to atorvastatin, atorvastatin monotherapy with placebo to sitagliptin, or sitagliptin plus atorvastatin) for 16 weeks (Phase A). During Phase B of the study (Weeks 16 through 54), participants received either sitagliptin plus atorvastatin with placebo to glimepiride or glimepiride plus atorvastatin with placebo to sitagliptin.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Atorvastatin
Other: Placebo to sitagliptin
Other: Placebo to atorvastatin
Drug: Metformin
Drug: Glimepiride
Drug: Placebo to glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Co-administration of Sitagliptin and Atorvastatin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from baseline in hemoglobin A1C (A1C) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Percent change from baseline in low density lipoprotein cholesterol (LDL-C) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in fasting plasma glucose (FPG) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Percent change from baseline in total cholesterol at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Percent change from baseline in apolipoprotein B (Apo B) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Percent change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Percent change from baseline in triglycerides at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Percent change from baseline in very low-density lipoprotein cholesterol (VLDL-C) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Percent change from baseline in high density lipoprotein cholesterol (HDL-C) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

Enrollment: 166
Study Start Date: October 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sitagliptin
Phase A: sitagliptin 100 mg orally daily plus matching placebo to atorvastatin for 16 weeks
Drug: Sitagliptin
Sitagliptin 100 mg orally daily
Other Name: Januvia
Other: Placebo to atorvastatin
Placebo to atorvastatin orally daily. Participants not meeting specific goals for low density lipoprotein cholesterol during Phase A will be switched to atorvastatin 80 mg.
Drug: Metformin
Participant will remain on prestudy dose of metformin (at leat 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Glimepiride
Phase A: Glimepiride 1 or 2 mg once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals. Phase B: glimepiride up to 6 mg daily with placebo to sitagliptin and atorvastatin 80 mg daily
Other Name: Amaryl
Active Comparator: Atorvastatin
Phase A: atorvastatin 80 mg orally daily plus matching placebo to sitagliptin for 16 weeks
Drug: Atorvastatin
Atorvastatin 80 mg orally daily
Other Name: Lipitor
Other: Placebo to sitagliptin
Placebo to sitagliptin orally daily
Drug: Metformin
Participant will remain on prestudy dose of metformin (at leat 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Glimepiride
Phase A: Glimepiride 1 or 2 mg once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals. Phase B: glimepiride up to 6 mg daily with placebo to sitagliptin and atorvastatin 80 mg daily
Other Name: Amaryl
Experimental: Sitagliptin + atorvastatin
Phase A: sitagliptin 100 mg tablet orally daily plus atorvastatin 80 mg tablet orally daily for 16 weeks
Drug: Sitagliptin
Sitagliptin 100 mg orally daily
Other Name: Januvia
Drug: Atorvastatin
Atorvastatin 80 mg orally daily
Other Name: Lipitor
Drug: Metformin
Participant will remain on prestudy dose of metformin (at leat 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Glimepiride
Phase A: Glimepiride 1 or 2 mg once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals. Phase B: glimepiride up to 6 mg daily with placebo to sitagliptin and atorvastatin 80 mg daily
Other Name: Amaryl
Active Comparator: Glimepiride + atorvastatin
Phase B: glimepiride up to 6 mg daily, placebo to sitagliptin, and atorvastatin 80 mg daily for Weeks 16 through 54
Drug: Atorvastatin
Atorvastatin 80 mg orally daily
Other Name: Lipitor
Other: Placebo to sitagliptin
Placebo to sitagliptin orally daily
Drug: Metformin
Participant will remain on prestudy dose of metformin (at leat 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Glimepiride
Phase A: Glimepiride 1 or 2 mg once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals. Phase B: glimepiride up to 6 mg daily with placebo to sitagliptin and atorvastatin 80 mg daily
Other Name: Amaryl
Experimental: Placebo to glimepiride + sitagliptin + atorvastatin
Phase B: matching placebo to glimepiride plus sitagliptin 100 mg daily and atorvastatin 80 mg daily for Weeks 16 through 54
Drug: Sitagliptin
Sitagliptin 100 mg orally daily
Other Name: Januvia
Drug: Atorvastatin
Atorvastatin 80 mg orally daily
Other Name: Lipitor
Drug: Metformin
Participant will remain on prestudy dose of metformin (at leat 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Placebo to glimepiride
Placebo to glimepiride orally daily

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • has type 2 diabetes mellitus
  • is a male, or a female who is highly unlikely to conceive
  • is currently on monotherapy with metformin (at least 1500 mg/day) for at least 8 weeks
  • is not on statin therapy or other lipid-lowering agents for at least 6 weeks

Exclusion Criteria:

  • has a history of type 1 diabetes mellitus, ketoacidosis or possibly has type 1 diabetes
  • has ever taken a dipeptidyl peptidase IV inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or a glucagon-like peptide-1 mimetic (such as exenatide or liraglutide), or has required insulin therapy within 12 weeks prior to signing informed consent
  • has been on a peroxisome proliferator-activated receptor gamma agonist within the prior 12 weeks
  • has been treated with a statin or other lipid-lowering agents, including over the counter supplements of fish oils within 6 weeks
  • intends to consume at least 1.2 liters of grapefruit juice per day during the course of the study
  • is on or is likely to require treatment with 14 consecutive days or more, or repeated courses of corticosteroids
  • is on a weight loss program and not in the maintenance phase or has started a weight loss medication (such as orlistat or sibutramine) within the prior 8 weeks
  • has undergone a surgical procedure within the prior 4 weeks
  • has a history of myopathy or rhabdomyolysis with any statin.
  • has cardiovascular disease
  • has New York Heart Association (NYHA) Class III or IV congestive heart failure, inadequately controlled hypertension, a medical history of active liver disease, chronic progressive neuromuscular disorder, is HIV positive, has a clinically significant hematological disorder, uncontrolled endocrine or metabolic disease known to influence glycemic control or serum lipids/lipoproteins, untreated hyperthyroidism or is currently under treatment for hyperthyroidism
  • has a history of malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
  • is pregnant or breastfeeding, or is intending to become pregnant or donate eggs within the projected duration of the study and post-study follow-up period
  • uses recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or increased alcohol consumption
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01477853     History of Changes
Other Study ID Numbers: 0431E-211
Study First Received: November 19, 2011
Last Updated: November 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Atorvastatin
Glimepiride
Metformin
Sitagliptin
Anti-Arrhythmia Agents
Anticholesteremic Agents
Antimetabolites
Cardiovascular Agents
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypoglycemic Agents
Hypolipidemic Agents
Immunologic Factors
Immunosuppressive Agents
Incretins
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014