A Double-Blind, Randomized, Active-Comparator (Metformin) Controlled, Clinical Trial to Study the Efficacy and Safety of the Strategy to Start Patients With Type 2 Diabetes Mellitus on Janumet™ Compared to Metformin

NCT ID: NCT00684528

Last Updated: 2012-03-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2012-12-31

Brief Summary

Comparison between the effectiveness of one anti-diabetic drug (Metformin, To combination of this drug and additional drug (Janufer), In the community setting.

Detailed Description

This is a randomized, double-blind, active-comparator (metformin) controlled study in drug-naïve patients with T2DM who have an HbA1c ≥ 7.5%. The duration of the study is 55 weeks, which will include a 1-week screening period (Visit 1 to Visit 2) and a 54 week double-blind, active treatment period. At Visit 2/Day 1 patients who meet all enrollment criteria will be randomized in a 1:1 ratio to one of two active treatment groups: 1. JANUMET™ (fixed-dose combination sitagliptin/metformin) or 2. metformin. The starting fixed-dose combination of sitagliptin/metformin will be 50/500 mg administered twice-daily and then up-titrated to a dose of 50/1000 mg b.i.d. over 4 weeks. The starting dose of metformin will be 500 mg twice-daily and then up-titrated to a dose of 1000 mg b.i.d. over 4 weeks. Patients who can not tolerate JANUMET™ at a dose of at least 50/500 mg b.i.d. or metformin at a dose of at least 500 mg b.i.d. 6 weeks after randomization and throughout the study will be discontinued. During the double-blind treatment period patients will remain on the study medication, but investigators are allowed to add other antihyperglycemic agents to improve glycemic control as necessary. The investigator can schedule additional visits to initiate additional antihyperglycemic agents or monitor glycemic control at any time during the study period. There will be no fixed visit schedule, but 7 clinical visits are recommended. It is also recommended to perform the first visit on active treatment 6 weeks after randomization and after this visit to schedule visits every 3 months. All clinical and lab data can be obtained using the "Clalit health care information system".

Conditions

Diabetes Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

a

This group will receive Metformin and placebo.

Group Type: ACTIVE_COMPARATOR

Metformin 1500 mg daily

Intervention Type: DRUG

500 mg thrice daily

2

The second arm will receive Metformin and Januvia

Group Type: EXPERIMENTAL

Metformin 1500 mg daily

Intervention Type: DRUG

500 mg thrice daily

Metformin + Janufer (Janumet)

Intervention Type: DRUG

Titration up to 1500/150 mg daily

Interventions

Metformin 1500 mg daily

500 mg thrice daily

Intervention Type: DRUG

Metformin + Janufer (Janumet)

Titration up to 1500/150 mg daily

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

Glucose Metabolism and Therapy Criteria

• Patient has a history of type 1 diabetes mellitus or history of ketoacidosis. Patients Requiring Specific Treatments
• Patient has symptomatic hyperglycemia requiring immediate initiation of insulin therapy.
• Patient has a history of intolerance or hypersensitivity to metformin or sitagliptin or has any contraindication to use metformin.

Concomitant Disease of Organs and Systems

• Patient has a medical history of active liver disease (excluding hepatic steatosis).
• Patient has severe active peripheral vascular disease (e.g., manifested by claudication with minimal activity, a non-healing ischemic ulcer, or disease which is likely to require intervention such as with bypass or angioplasty).
• Patient has unstable or acute congestive heart failure.
• Patient has a history of malignancy without documentation of remission/cure. Other Criteria
• Patient is pregnant, has a positive urine pregnancy test at Visit 1, is expecting to conceive within the projected duration of the study, or is breast feeding.

• Patient has increased serum-creatinine and/or decreased estimated creatinine clearance.
• If screening labs are repeated, the last laboratory draw/result should be used for inclusion.§ Either elevated Creatinine or decreased estimated creatinine clearance lead to exclusion of the patient.

At Visit 2

• Patient has a site fingerstick glucose <130 mg/dL (7.2 mmol/L) or >320 mg/dL (17.8 mmol/L).

Note: If the patient meets this exclusion criterion AND the investigator believes that the value does not reflect the patient's recent glycemic control based upon recent SBGM values and/or the Visit 1 FPG value, the patient should not be excluded at this time. The current visit should be changed to an "Unscheduled visit" and the patient should be rescheduled for Visit 2. If, at the rescheduled Visit 2, the patient meets this exclusion criterion, the patient MUST be excluded.

• Patient has a positive urine pregnancy test.
• Patient developed a new medical condition, suffered a change in status of an established medical condition, developed a laboratory abnormality, or required a new treatment or medication between Visit 1 and Visit 2 which meets any previously described study exclusion criterion.

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

Sponsors

Clalit Health Services

OTHER

Sponsor Role: collaborator

Meir Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joel Zinger, MD

Role: PRINCIPAL_INVESTIGATOR

clali health organization

Locations

Clalit Health services center

Tel Aviv, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Niky Liberman, MD

Role: CONTACT

nikyli@clalit.org.il

972-3692-3316

Lotan Shilo, MD

Role: CONTACT

shilolo@clalit.org.il

972-9747-2170

Facility Contacts

Zinger

Role: primary

972-5062-63652

References

Mistry GC, Maes AL, Lasseter KC, Davies MJ, Gottesdiener KM, Wagner JA, Herman GA. Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patients with mild to moderate hypertension. J Clin Pharmacol. 2008 May;48(5):592-8. doi: 10.1177/0091270008316885. Epub 2008 Mar 19.

Reference Type: BACKGROUND

PMID: 18353996 (View on PubMed)

Scott R, Loeys T, Davies MJ, Engel SS; Sitagliptin Study 801 Group. Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2008 Sep;10(10):959-69. doi: 10.1111/j.1463-1326.2007.00839.x. Epub 2008 Jan 14.

Reference Type: RESULT

PMID: 18201203 (View on PubMed)

Other Identifiers

jfr_il0801

Identifier Type: -

Identifier Source: org_study_id