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

NCT00722371 | Completed Phase 3 Results

• 2 other identifiers: 0431-1022008_522
• Study Type: interventional
• Target: 1,615
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Hemoglobin A1C (A1C) at Week 24

  A1C represents the percentage of glycosylated hemoglobin.

  Baseline and Week 24

• Change From Baseline in A1C at Week 54

  A1C represents the percentage of glycosylated hemoglobin.

  Baseline and Week 54

Secondary Outcomes (4)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

  Baseline and Week 24

• Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 24

  Baseline and Week 24

• Change From Baseline in FPG at Week 54

  Baseline and Week 54

• Change From Baseline in 2-Hour PMG at Week 54

  Baseline and Week 54

Study Arms (7)

Sitagliptin 100 mg

EXPERIMENTAL

Drug: Sitagliptin phosphate; Drug: Matching placebo to pioglitazone; Drug: Metformin

Pioglitazone 15 mg

EXPERIMENTAL

Drug: Pioglitazone hydrochloride; Drug: Matching placebo to sitagliptin; Drug: Metformin

Pioglitazone 30 mg

EXPERIMENTAL

Drug: Pioglitazone hydrochloride; Drug: Matching placebo to sitagliptin; Drug: Metformin

Pioglitazone 45 mg

EXPERIMENTAL

Drug: Pioglitazone hydrochloride; Drug: Matching placebo to sitagliptin; Drug: Metformin

Sitagliptin 100 mg/ Pioglitazone 15 mg

EXPERIMENTAL

Drug: Sitagliptin phosphate; Drug: Pioglitazone hydrochloride; Drug: Metformin

Sitagliptin 100 mg/ Pioglitazone 30 mg

EXPERIMENTAL

Drug: Sitagliptin phosphate; Drug: Pioglitazone hydrochloride; Drug: Metformin

Sitagliptin 100 mg/ Pioglitazone 45 mg

EXPERIMENTAL

Drug: Sitagliptin phosphate; Drug: Pioglitazone hydrochloride; Drug: Metformin

Interventions

Sitagliptin phosphate DRUG

Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks.

Also known as: Januvia, Tesavel, Xelevia, Ristaben

Sitagliptin 100 mg; Sitagliptin 100 mg/ Pioglitazone 15 mg; Sitagliptin 100 mg/ Pioglitazone 30 mg; Sitagliptin 100 mg/ Pioglitazone 45 mg

Pioglitazone hydrochloride DRUG

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.

Also known as: Actos

Pioglitazone 15 mg; Pioglitazone 30 mg; Pioglitazone 45 mg; Sitagliptin 100 mg/ Pioglitazone 15 mg; Sitagliptin 100 mg/ Pioglitazone 30 mg; Sitagliptin 100 mg/ Pioglitazone 45 mg

Matching placebo to sitagliptin DRUG

Matching placebo to sitagliptin orally once daily for 54 weeks.

Pioglitazone 15 mg; Pioglitazone 30 mg; Pioglitazone 45 mg

Matching placebo to pioglitazone DRUG

Matching placebo to pioglitazone tablets or capsules orally once daily for 54 weeks.

Sitagliptin 100 mg

Metformin DRUG

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.

Pioglitazone 15 mg; Pioglitazone 30 mg; Pioglitazone 45 mg; Sitagliptin 100 mg; Sitagliptin 100 mg/ Pioglitazone 15 mg; Sitagliptin 100 mg/ Pioglitazone 30 mg; Sitagliptin 100 mg/ Pioglitazone 45 mg

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 %

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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):223-30. doi: 10.1111/dom.12194. Epub 2013 Aug 29.

  PMID: 23909985 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Pioglitazone; Metformin

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; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Biguanides; Guanidines; Amidines

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

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: July 22, 2008
• First Posted: July 25, 2008
• Study Start: September 5, 2008
• Primary Completion: October 26, 2010
• Study Completion: March 25, 2011
• Last Updated: May 12, 2017
• Results First Posted: October 17, 2011

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share