MK0431 (Sitagliptin) and Metformin Co-Administration Factorial Study in Patients With Type 2 Diabetes Mellitus (0431-036)

NCT ID: NCT00103857

Last Updated: 2017-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1208 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-17
• Study Completion Date: 2008-02-21

Brief Summary

The purpose of this study is to determine the safety and effectiveness of an investigational drug in patients with Type 2 Diabetes Mellitus (T2DM) (a specific type of diabetes).

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

MK0431 100 mg q.d.

Group Type: EXPERIMENTAL

Comparator: MK0431 100 mg q.d. (q.d. = once daily)

Intervention Type: DRUG

MK0431 oral tablets will be started on Day 1 as two 50 mg tablets (100 mg q.d.) (q.d. = once daily) and continued at this dose throughout the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

2

Metformin 500 mg b.i.d.

Group Type: ACTIVE_COMPARATOR

Comparator: Metformin 500 mg b.i.d.

Intervention Type: DRUG

Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased after 1 week to a stable dose of 500 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 500 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

3

Metformin 1000 mg b.i.d.

Group Type: ACTIVE_COMPARATOR

Comparator: Metformin 1000 mg b.i.d.

Intervention Type: DRUG

Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 1000 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

4

Coadministration of MK0431 and Metformin 50/500 mg b.i.d.

Group Type: EXPERIMENTAL

Comparator: MK0431 50 mg b.i.d. (b.i.d. = twice daily)

Intervention Type: DRUG

MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take MK0431 50 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

Comparator: Metformin 500 mg b.i.d.

Intervention Type: DRUG

Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased after 1 week to a stable dose of 500 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 500 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

5

Coadministration of MK0431 and Metformin 50/1000 mg b.i.d.

Group Type: EXPERIMENTAL

Comparator: MK0431 50 mg b.i.d. (b.i.d. = twice daily)

Intervention Type: DRUG

MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take MK0431 50 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

Comparator: Metformin 1000 mg b.i.d.

Intervention Type: DRUG

Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 1000 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

6

Placebo/Metformin 1000 mg b.i.d.

Group Type: PLACEBO_COMPARATOR

Comparator: Placebo (Phase A)/Metformin (Phase B)

Intervention Type: DRUG

During the placebo-controlled period (Day 1 through Week 24/Phase A), metformin and MK0431 matching placebos will be dispensed as oral tablets. At the beginning of the 30-week active-controlled period (Phase B), metformin will be started as 500 mg q.d. (q.d. = once daily) and up-titrated in 500 mg weekly increments to a stable dose of 1000 mg b.i.d. Patients who complete the 54-week base study and who enter the 50-week extension study will continue to take metformin 1000 mg b.i.d. (b.i.d. = twice daily) for a total placebo/metformin treatment duration of up to 104 weeks.

7

Non-Randomized, Open-Label: Coadministration MK0431 and Metformin 50/1000 mg b.i.d.

Group Type: EXPERIMENTAL

Comparator: Open-Label MK0431/Metformin 50/1000 mg b.i.d.

Intervention Type: DRUG

MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Metformin oral tablets will be started on Day 1 at 500 mg q.d. and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. The open-label treatment period is 24 weeks.

Interventions

Comparator: MK0431 50 mg b.i.d. (b.i.d. = twice daily)

MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take MK0431 50 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

Intervention Type: DRUG

Comparator: MK0431 100 mg q.d. (q.d. = once daily)

MK0431 oral tablets will be started on Day 1 as two 50 mg tablets (100 mg q.d.) (q.d. = once daily) and continued at this dose throughout the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

Intervention Type: DRUG

Comparator: Placebo (Phase A)/Metformin (Phase B)

During the placebo-controlled period (Day 1 through Week 24/Phase A), metformin and MK0431 matching placebos will be dispensed as oral tablets. At the beginning of the 30-week active-controlled period (Phase B), metformin will be started as 500 mg q.d. (q.d. = once daily) and up-titrated in 500 mg weekly increments to a stable dose of 1000 mg b.i.d. Patients who complete the 54-week base study and who enter the 50-week extension study will continue to take metformin 1000 mg b.i.d. (b.i.d. = twice daily) for a total placebo/metformin treatment duration of up to 104 weeks.

Intervention Type: DRUG

Comparator: Metformin 500 mg b.i.d.

Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased after 1 week to a stable dose of 500 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 500 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

Intervention Type: DRUG

Comparator: Open-Label MK0431/Metformin 50/1000 mg b.i.d.

MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Metformin oral tablets will be started on Day 1 at 500 mg q.d. and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. The open-label treatment period is 24 weeks.

Intervention Type: DRUG

Comparator: Metformin 1000 mg b.i.d.

Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 1000 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.

Intervention Type: DRUG

Other Intervention Names

MK0431

Eligibility Criteria

Inclusion Criteria

54-Week Base Study:

• Patients between the ages of 18 and 78 with Type 2 Diabetes Mellitus (a specific type of diabetes)

50-Week Extension Study:

• Patients who complete the 54-week base study are eligible to enter the 50-week extension study

Exclusion Criteria

• Patients who do not have Type 2 Diabetes Mellitus (a specific type of diabetes)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 78 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007 Aug;30(8):1979-87. doi: 10.2337/dc07-0627. Epub 2007 May 7.

Reference Type: BACKGROUND

PMID: 17485570 (View on PubMed)

Gnesin F, Thuesen ACB, Kahler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Jun 5;6(6):CD012906. doi: 10.1002/14651858.CD012906.pub2.

Reference Type: DERIVED

PMID: 32501595 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

MK0431-036

Identifier Type: -

Identifier Source: secondary_id

2005_003

Identifier Type: -

Identifier Source: secondary_id

0431-036

Identifier Type: -

Identifier Source: org_study_id