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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01477853
• Other study ID #: 0431E-211
• Secondary ID: 2011-003600-20
• Status: Terminated
• Phase: Phase 3
• Start date: October 24, 2011
• Est. completion date: December 4, 2012

Study information

• Verified date: July 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 166
• Est. completion date: December 4, 2012
• Est. primary completion date: December 4, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sitagliptin
Sitagliptin 100 mg tablet orally daily
• Atorvastatin
Atorvastatin 80 mg tablet orally daily

Other:
• Placebo to sitagliptin
Placebo to sitagliptin tablet orally daily
• 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.
• 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.
• Glimepiride (double-blind)
Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.
• Placebo to glimepiride
Phase B: placebo to glimepiride tablet orally daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1C (A1C) at Week 16	A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.	Baseline and Week 16
Primary	Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Primary	Number of Participants Who Experienced at Least One Adverse Event	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.	Up to 56 weeks (including 2-week follow-up)
Primary	Number of Participants Who Discontinued Study Drug Due to an Adverse Event	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.	Up to 54 weeks
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16	Change from baseline reflects the Week 16 value minus the Week 0 value.	Baseline and Week 16
Secondary	Percent Change From Baseline in Total Cholesterol at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Triglycerides at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16