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

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Sitagliptin phosphate Drug: Pioglitazone hydrochloride Drug: Matching placebo to sitagliptin Drug: Matching placebo to pioglitazone Drug: Metformin	Phase 3

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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Pioglitazone Pioglitazone hydrochloride Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Change From Baseline in Hemoglobin A1C (A1C) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
A1C represents the percentage of glycosylated hemoglobin.
Change From Baseline in A1C at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
A1C represents the percentage of glycosylated hemoglobin.

Secondary Outcome Measures:

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
PMG was measured using the Meal Tolerance Test (MTT).
Change From Baseline in FPG at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
Change From Baseline in 2-Hour PMG at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
PMG was measured using the Meal Tolerance Test (MTT).

Enrollment:	1615
Study Start Date:	September 2008
Study Completion Date:	March 2011
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sitagliptin 100 mg	Drug: Sitagliptin phosphate Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks. Other Names: Januvia Tesavel Xelevia Ristaben Drug: Matching placebo to pioglitazone Matching placebo to pioglitazone tablets or capsules orally once daily for 54 weeks. Drug: 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.
Experimental: Pioglitazone 15 mg	Drug: 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. Other Name: Actos Drug: Matching placebo to sitagliptin Matching placebo to sitagliptin orally once daily for 54 weeks. Drug: 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.
Experimental: Pioglitazone 30 mg	Drug: 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. Other Name: Actos Drug: Matching placebo to sitagliptin Matching placebo to sitagliptin orally once daily for 54 weeks. Drug: 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.
Experimental: Pioglitazone 45 mg	Drug: 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. Other Name: Actos Drug: Matching placebo to sitagliptin Matching placebo to sitagliptin orally once daily for 54 weeks. Drug: 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.
Experimental: Sitagliptin 100 mg/ Pioglitazone 15 mg	Drug: Sitagliptin phosphate Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks. Other Names: Januvia Tesavel Xelevia Ristaben Drug: 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. Other Name: Actos Drug: 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.
Experimental: Sitagliptin 100 mg/ Pioglitazone 30 mg	Drug: Sitagliptin phosphate Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks. Other Names: Januvia Tesavel Xelevia Ristaben Drug: 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. Other Name: Actos Drug: 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.
Experimental: Sitagliptin 100 mg/ Pioglitazone 45 mg	Drug: Sitagliptin phosphate Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks. Other Names: Januvia Tesavel Xelevia Ristaben Drug: 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. Other Name: Actos Drug: 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.

Eligibility

Ages Eligible for Study:	18 Years to 78 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00722371 History of Changes
Other Study ID Numbers:	MK-0431-102, 2008_522
Study First Received:	July 22, 2008
Results First Received:	September 9, 2011
Last Updated:	September 9, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Sitagliptin
Metformin

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2013