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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.
(The study was terminated early by the Sponsor for business reasons.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01477853
First received: November 19, 2011
Last updated: August 11, 2016
Last verified: August 2016
  Purpose
This two-phase study was to 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 to be randomized to one of three treatment arms (sitagliptin monotherapy, atorvastatin monotherapy, or sitagliptin plus atorvastatin) for 16 weeks (Phase A). During Phase B of the study (Weeks 16 through 54), participants were to receive either sitagliptin plus atorvastatin or glimepiride plus atorvastatin. The primary hypotheses were that after 16 weeks of treatment, sitagliptin in combination with atorvastatin reduces A1C from baseline more than atorvastatin alone, and that atorvastatin in combination with sitagliptin lowers LDL-C from baseline more than sitagliptin alone.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Atorvastatin
Other: Placebo to sitagliptin
Other: Placebo to atorvastatin
Drug: Metformin (open-label)
Drug: Glimepiride (open-label)
Drug: Glimepiride (double-blind)
Drug: Placebo to glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/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 ]
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.

  • 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 ]
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

  • Number of Participants Who Experienced at Least One Adverse Event [ Time Frame: Up to 56 weeks (including 2-week follow-up) ] [ Designated as safety issue: Yes ]
    An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.

  • Number of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 54 weeks ] [ Designated as safety issue: Yes ]
    An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.


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 ]
    Change from baseline reflects the Week 16 value minus the Week 0 value.

  • 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 was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

  • 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 was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

  • 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 was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

  • Percent Change From Baseline in Triglycerides at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

  • 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 was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

  • 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 ]
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.


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
Experimental: Sitagliptin/Sitagliptin + Atorvastatin
In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
Drug: Sitagliptin
Sitagliptin 100 mg tablet orally daily
Other Name: Januvia
Drug: Atorvastatin
Atorvastatin 80 mg tablet orally daily
Other Name: Lipitor
Other: Placebo to atorvastatin
Placebo to atorvastatin tablet orally daily.
Drug: Metformin (open-label)
Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Glimepiride (open-label)
Phase A: Glimepiride 1 or 2 mg tablet 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.
Other Name: Amaryl
Drug: Placebo to glimepiride
Phase B: placebo to glimepiride tablet orally daily.
Active Comparator: Atorvastatin/Atorvastatin + Glimepiride
In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.
Drug: Atorvastatin
Atorvastatin 80 mg tablet orally daily
Other Name: Lipitor
Other: Placebo to sitagliptin
Placebo to sitagliptin tablet orally daily
Drug: Metformin (open-label)
Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Glimepiride (double-blind)
Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.
Experimental: Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
Drug: Sitagliptin
Sitagliptin 100 mg tablet orally daily
Other Name: Januvia
Drug: Atorvastatin
Atorvastatin 80 mg tablet orally daily
Other Name: Lipitor
Drug: Metformin (open-label)
Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.
Other Name: Glucophage
Drug: Glimepiride (open-label)
Phase A: Glimepiride 1 or 2 mg tablet 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.
Other Name: Amaryl
Drug: Placebo to glimepiride
Phase B: placebo to glimepiride tablet orally daily.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years   (Adult, Senior)
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 human immunodeficiency virus (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.

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

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01477853     History of Changes
Other Study ID Numbers: 0431E-211  2011-003600-20 
Study First Received: November 19, 2011
Results First Received: June 21, 2016
Last Updated: August 11, 2016
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
Metformin
Sitagliptin Phosphate
Atorvastatin Calcium
Hypoglycemic Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Anti-Arrhythmia Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on December 06, 2016