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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

November 19, 2011
August 11, 2016
October 2011
December 2012   (final data collection date for primary outcome measure)
  • 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.
  • 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 ]
Complete list of historical versions of study NCT01477853 on ClinicalTrials.gov Archive Site
  • 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%.
  • 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 ]
Not Provided
Not Provided
 
A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • 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 sitagliptin
    Placebo to sitagliptin tablet orally daily
  • 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: Glimepiride (double-blind)
    Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.
  • Drug: Placebo to glimepiride
    Phase B: placebo to glimepiride tablet orally daily.
  • 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.
    Interventions:
    • Drug: Sitagliptin
    • Drug: Atorvastatin
    • Other: Placebo to atorvastatin
    • Drug: Metformin (open-label)
    • Drug: Glimepiride (open-label)
    • Drug: Placebo to glimepiride
  • 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.
    Interventions:
    • Drug: Atorvastatin
    • Other: Placebo to sitagliptin
    • Drug: Metformin (open-label)
    • Drug: Glimepiride (double-blind)
  • 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.
    Interventions:
    • Drug: Sitagliptin
    • Drug: Atorvastatin
    • Drug: Metformin (open-label)
    • Drug: Glimepiride (open-label)
    • Drug: Placebo to glimepiride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
166
December 2012
December 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 79 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
Canada,   Korea, Republic of,   Mexico,   Romania,   South Africa,   United States
 
NCT01477853
0431E-211, 2011-003600-20
No
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP