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

NCT01477853 | Terminated Phase 3 Results

• 2 other identifiers: 0431E-2112011-003600-20
• Study Type: interventional
• Target: 166
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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)

• 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 Outcomes (7)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16

  Baseline and Week 16

• Percent Change From Baseline in Total Cholesterol at Week 16

  Baseline and Week 16

• Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16

  Baseline and Week 16

• Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16

  Baseline and Week 16

• Percent Change From Baseline in Triglycerides at Week 16

  Baseline and Week 16

Study Arms (3)

Sitagliptin/Sitagliptin + Atorvastatin

EXPERIMENTAL

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; Drug: Atorvastatin; Other: Placebo to atorvastatin; Drug: Metformin (open-label); Drug: Glimepiride (open-label); Drug: Placebo to glimepiride

Atorvastatin/Atorvastatin + Glimepiride

ACTIVE COMPARATOR

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; Other: Placebo to sitagliptin; Drug: Metformin (open-label); Drug: Glimepiride (double-blind)

Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin

EXPERIMENTAL

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; Drug: Atorvastatin; Drug: Metformin (open-label); Drug: Glimepiride (open-label); Drug: Placebo to glimepiride

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg tablet orally daily

Also known as: Januvia

Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin; Sitagliptin/Sitagliptin + Atorvastatin

Atorvastatin DRUG

Atorvastatin 80 mg tablet orally daily

Also known as: Lipitor

Atorvastatin/Atorvastatin + Glimepiride; Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin; Sitagliptin/Sitagliptin + Atorvastatin

Placebo to sitagliptin OTHER

Placebo to sitagliptin tablet orally daily

Atorvastatin/Atorvastatin + Glimepiride

Placebo to atorvastatin OTHER

Placebo to atorvastatin tablet orally daily.

Sitagliptin/Sitagliptin + Atorvastatin

Metformin (open-label) DRUG

Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.

Also known as: Glucophage

Atorvastatin/Atorvastatin + Glimepiride; Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin; Sitagliptin/Sitagliptin + Atorvastatin

Glimepiride (open-label) DRUG

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.

Also known as: Amaryl

Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin; Sitagliptin/Sitagliptin + Atorvastatin

Glimepiride (double-blind) DRUG

Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.

Atorvastatin/Atorvastatin + Glimepiride

Placebo to glimepiride DRUG

Phase B: placebo to glimepiride tablet orally daily.

Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin; Sitagliptin/Sitagliptin + Atorvastatin

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Atorvastatin; Metformin; glimepiride; Double-Blind Method

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Pyrroles; Heptanoic Acids; Fatty Acids; Lipids; Biguanides; Guanidines; Amidines; Organic Chemicals; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Limitations and Caveats

The study was terminated early by the Sponsor for business reasons. Due to the small number of participants included in the FAS, the results for Phase A and for the overall study should be interpreted with caution.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2011
• First Posted: November 23, 2011
• Study Start: October 24, 2011
• Primary Completion: December 4, 2012
• Study Completion: December 4, 2012
• Last Updated: July 26, 2018
• Results First Posted: October 5, 2016

Record last verified: 2018-07