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

Condition(s) targeted: Diabetes Type 2

Intervention: Metformin 1500 mg daily (Drug); Metformin + Janufer (Janumet) (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Meir Medical Center

Official(s) and/or principal investigator(s):
Joel Zinger, MD, Principal Investigator, Affiliation: clali health organization

Overall contact:
Niky Liberman, MD, Phone: 972-3692-3316, Email: nikyli@clalit.org.il

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

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

Primary outcome:

The efficacy and safety of community based study in diabetic patients, comparing Metformin to Metformin + Janufer.

The efficacy and safety of Metformin VS Metformin + 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".

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- All laboratory measurements are to be performed after an overnight fast ≥ 10 hours in

duration. Patients with laboratory screening values/findings not meeting protocol inclusion criteria may, at the discretion of the investigator, have one repeat determination performed. If the repeat value satisfies the criterion they may continue in the screening process. Only the laboratory test not meeting inclusion should be repeated (not the entire panel).

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.

Exclusion Criteria Based on Lab Abnormalities

- 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.

- Patients whose serum creatinine does not meet the exclusion criteria, but whose

estimated creatinine clearance is <60 mL/min but ≥50 mL/min, may have a measured creatinine clearance (i. e., based upon a 24-hour urine collection). These patients may be eligible if their measured creatinine clearance is ≥60 mL/min.

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.

Niky Liberman, MD, Phone: 972-3692-3316, Email: nikyli@clalit.org.il

Clalit Health services center, Tel Aviv 62098, Israel

Related publications:

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. Epub 2008 Mar 19.

Starting date: June 2008
Last updated: May 23, 2008