Study of Sitagliptin for the Treatment of Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Insulin (MK-0431-260)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Study the Safety and Insulin-Sparing Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Alone or in Combination With Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01462266
• Other study ID #: 0431-260
• Status: Completed
• Phase: Phase 3
• Start date: January 13, 2012
• Est. completion date: June 7, 2013

Study information

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

Clinical Trial Summary

The purpose of this study is to examine the insulin-sparing effect of sitagliptin 100 mg once-daily compared with placebo over 24 weeks in participants with type 2 diabetes mellitus who have inadequate glycemic control on insulin alone or in combination with metformin. The primary hypothesis of this study is that after 24 weeks, sitagliptin reduces the dose of insulin relative to placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 660
• Est. completion date: June 7, 2013
• Est. primary completion date: June 6, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• has type 2 diabetes mellitus

• has one of the following criteria:

• diagnosed with diabetes after age 40 years and insulin therapy was initiated at least 3 years following diagnosis

• if diagnosed with diabetes under age 40 years or insulin started earlier than 3 years after diagnosis, has a fasting C-peptide greater than 0.7 ng/mL

• must be at least 18 years of age and less than or equal to 80 years of age (for participants in India: must be at least 18 years of age and less than or equal to 65 years of age)

• on a stable regimen of insulin for at least 10 weeks with or without metformin (at least 1500 mg/day) and/or sulfonylurea for at least 10 weeks

• is highly unlikely to become pregnant (not of reproductive potential or agrees to remain abstinent or use (or have their partner use) an acceptable method of birth control during the study and for 14 days after the last dose of study medication

Exclusion Criteria:

• has been treated with a dipeptidyl peptidase IV (DPP-4) inhibitor, a thiazolidinedione (TZD), or a glucagon-like peptide-1 (GLP-1) mimetic or analogue, within the past 12 weeks

• currently on treatment with daily use (one or more injections per day) of a

pre-prandial short-acting or rapid-acting insulin alone or as part of a basal/bolus insulin regimen

• has symptomatic hyperglycemia that requires immediate initiation, adjustment, or addition of antihyperglycemic therapy

• has a history of 2 or more episodes of hypoglycemia resulting in seizure,

coma, or loss of consciousness, - or - has had recurrent (=3 times per week) episodes of hypoglycemia over the past 8 weeks

• has a history of ketoacidosis

• is not appropriate for or does not agree to target a fasting glucose of 72-100 mg/dL [4.0-5.6 mmol/L]

• is on or likely to require treatment with corticosteroids

• has undergone a surgical procedure within 4 weeks or has planned major surgery during the study

• is currently being treated for hyperthyroidism or is on thyroid hormone

therapy and has not been on a stable dose for at least 6 weeks

• has a history of active liver disease (other than non-alcoholic hepatic

steatosis)

• has had new or worsening signs or symptoms of coronary heart disease or

congestive heart failure within the past 3 months, or has any of the following

disorders within the past 3 months:

• acute coronary syndrome

• coronary artery intervention

• stroke or transient ischemic neurological disorder

• has a systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure greater than 90 mm Hg

• has human immunodeficiency virus (HIV)

• has severe peripheral vascular disease

• has a clinically important hematological disorder

• has a history of malignancy that is less than 5 years from study start, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer

• has a positive urine pregnancy test

• is pregnant or breast-feeding, or is expecting to conceive or donate eggs

during the study

• a user of recreational or illicit drugs or has had a recent history of drug abuse

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sitagliptin
Sitagliptin 100 mg tablet once daily for 24 weeks
• Comparator: Placebo
Placebo to sitagliptin once daily for 24 weeks

Biological:
• Insulin Glargine
Participants on insulin glargine or another insulin regimen for at least 10 weeks prior to screening will continue or switch to open-label insulin glargine once-daily in the evening for the duration of the study.

Drug:
• Metformin
Participants on metformin oral tablet(s) at a dose of at least 1500 mg/day for at least 10 weeks prior to screening will continue receiving metformin at their current dose for the duration of the study.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Mathieu C, Shankar RR, Lorber D, Umpierrez G, Wu F, Xu L, Golm GT, Latham M, Kaufman KD, Engel SS. A Randomized Clinical Trial to Evaluate the Efficacy and Safety of Co-Administration of Sitagliptin with Intensively Titrated Insulin Glargine. Diabetes The — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Daily Insulin Dose at Week 24	Change in daily insulin dose following 24 weeks of therapy (i.e., daily insulin dose at Week 24 minus daily insulin dose at baseline)	Baseline and Week 24
Secondary	Change From Baseline in Hemoglobin A1c (A1C) at Week 24	A1C is measured as the percentage of glycosylated hemoglobin. Change in A1C following 24 weeks of therapy (i.e., A1C at Week 24 minus A1C at baseline)	Baseline and Week 24
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Change in FPG (before breakfast) following 24 weeks of therapy (i.e., FPG at Week 24 minus FPG at baseline)	Baseline and Week 24
Secondary	Percent of Participants Achieving Fasting Glucose Target at Any Time During the Study	The fasting glucose target was defined as 3 consecutive days with a fingerstick glucose of 72 to 100 mg/dL (4.0 - 5.6 mmol/L).	Up to 24 weeks
Secondary	Time to Achieve the Fasting Glucose Target	Fasting glucose target 3 consecutive days with a fingerstick glucose of 72 to 100 mg/dL (4.0 - 5.6 mmol/L). This analysis was the Kaplan-Meier estimated 50th percentile of time (days) to first attainment of target.	Up to 24 weeks