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

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

Overview[ - collapse ][ - ]

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	Type 2 Diabetes Mellitus
Intervention	Drug: Sitagliptin Drug: Atorvastatin Other: Placebo to sitagliptin Other: Placebo to atorvastatin Drug: Metformin Drug: Glimepiride Drug: Placebo to glimepiride
Phase	Phase 3
Sponsor	Merck Sharp & Dohme Corp.
Responsible Party	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier	NCT01477853
First Received	November 19, 2011
Last Updated	November 22, 2013
Last verified	November 2013

Tracking Information[ + expand ][ + ]

First Received Date	November 19, 2011
Last Updated Date	November 22, 2013
Start Date	October 2011
Estimated Primary Completion Date	December 2012
Current 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]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief Title	A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211 AM1)
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
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Sitagliptin Sitagliptin 100 mg orally daily Other Names: JanuviaDrug: Atorvastatin Atorvastatin 80 mg orally daily Other Names: LipitorOther: Placebo to sitagliptin Placebo to sitagliptin orally daily 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 Names: GlucophageDrug: 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 Names: AmarylDrug: Placebo to glimepiride Placebo to glimepiride orally daily
Study Arm (s)	Active Comparator: Sitagliptin Phase A: sitagliptin 100 mg orally daily plus matching placebo to atorvastatin for 16 weeks Active Comparator: Atorvastatin Phase A: atorvastatin 80 mg orally daily plus matching placebo to sitagliptin for 16 weeks Experimental: Sitagliptin + atorvastatin Phase A: sitagliptin 100 mg tablet orally daily plus atorvastatin 80 mg tablet orally daily for 16 weeks 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 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

Recruitment Information[ + expand ][ + ]

Recruitment Status	Terminated
Estimated Enrollment	166
Estimated Completion Date	December 2012
Estimated Primary Completion Date	December 2012
Eligibility 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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Not Provided

Administrative Information[ + expand ][ + ]

NCT Number	NCT01477853
Other Study ID Numbers	0431E-211
Has Data Monitoring Committee	No
Information Provided By	Merck Sharp & Dohme Corp.
Study Sponsor	Merck Sharp & Dohme Corp.
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	November 2013