MK0431 and Pioglitazone Co-Administration Factorial Study in Patients With Type 2 Diabetes Mellitus (0431-102 AM2)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind Study of the Co-Administration of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00722371
• Other study ID #: 0431-102
• Secondary ID: 2008_522
• Status: Completed
• Phase: Phase 3
• First received: July 22, 2008
• Last updated: March 23, 2015
• Start date: September 2008
• Est. completion date: March 2011

Study information

• Verified date: March 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

A study to evaluate the efficacy and safety of sitagliptin and pioglitazone co-administration in comparison with sitagliptin and pioglitazone monotherapy in patients with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1615
• Est. completion date: March 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

Inclusion Criteria:

• Patient is highly unlikely to conceive

• Patient meets one of the 3 categories is naïve to all antihyperglycemic agent (AHA) therapies, or is non-naïve based upon the patient's current diet, medical regimen and screening A1c patient is currently not on AHA with a screening A1c >=7.5 % and =<11.0 % patient is currently on either metformin pr sulfonylurea monotherapy with a screening A1c >=7.0 % and =<9.0 %

Exclusion Criteria

• Patient has a history of type 1 diabetes mellitus or history of ketoacidosis or has C=peptide value of =<0.8 ng/mL

• Patient has previously been treated with insulin, thiazolidinedione (TZD) (rosiglitazone or pioglitazone), any Dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin, vildagliptin, or alogliptin), exenatide or has previously been in a clinical study with any DPP-4 inhibitor or incretin mimetic

• Patient is on a weight loss program and is not in the maintenance phase or has started a weight loss medication (e.g. orlistat or sibutramine) within the prior 8 weeks

• Patient has undergone surgery within the prior 30 days or has major surgery planned during the study

• Patient has a medical history of active liver disease including chronic active hepatitis B or C or symptomatic gallbladder disease including primary biliary cirrhosis

• Patient has received treatment with an investigational product within 12 weeks prior to Visit 1

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sitagliptin phosphate
Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks.
• Pioglitazone hydrochloride
Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.
• Matching placebo to sitagliptin
Matching placebo to sitagliptin orally once daily for 54 weeks.
• Matching placebo to pioglitazone
Matching placebo to pioglitazone tablets or capsules orally once daily for 54 weeks.
• Metformin
Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Henry RR, Staels B, Fonseca VA, Chou MZ, Teng R, Golm GT, Langdon RB, Kaufman KD, Steinberg H, Goldstein BJ. Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone--a factorial study. Diabetes Obes Metab. 2014 Mar;16(3):223 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1C (A1C) at Week 24	A1C represents the percentage of glycosylated hemoglobin.	Baseline and Week 24	No
Primary	Change From Baseline in A1C at Week 54	A1C represents the percentage of glycosylated hemoglobin.	Baseline and Week 54	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24		Baseline and Week 24	No
Secondary	Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 24	PMG was measured using the Meal Tolerance Test (MTT).	Baseline and Week 24	No
Secondary	Change From Baseline in FPG at Week 54		Baseline and Week 54	No
Secondary	Change From Baseline in 2-Hour PMG at Week 54	PMG was measured using the Meal Tolerance Test (MTT).	Baseline and Week 54	No