A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211 AM1) - Full Text View

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:

MedlinePlus related topics: Cholesterol Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Glimepiride Atorvastatin calcium Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by Merck:

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01477853

Show 64 Study Locations

Sponsors and Collaborators

Merck

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT01477853 History of Changes
Other Study ID Numbers:	0431E-211
Study First Received:	November 19, 2011
Last Updated:	December 12, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Sitagliptin
Metformin
Atorvastatin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013