VERIFY:A Study to Compare Combination Regimen With Vildagliptin & Metformin Versus Metformin in Treatment-naïve Patients With Type 2 Diabetes Mellitus

Novartis

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Metformin; Drug: Placebo of vildagliptin; Drug: vildagliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01528254

2011-003712-23 (EudraCT Number)

CLAF237A23156

Details and patient eligibility

About

The purpose of this study was to determine whether the initiation of a vildagliptin plus metformin combination regimen would result in more durable glycemic control than metformin monotherapy in treatment-naïve patients with type-2 diabetes mellitus (T2DM).

Full description

This was a multi-center, double-blind, placebo-controlled, 2-arm, parallel group study with a run-in period and up to 5 years treatment period. Following a screening visit (Visit 1) and a screening period of up to 2 weeks, treatment-naïve patients, meeting all eligibility criteria entered the run-in period at Visit 2.

• Run-in period: At Visit 2, in all eligible patients, metformin treatment was initiated and/or up-titrated. At the end of the 3-week run-in period, patients who were able to tolerate a total dose of at least 1000 mg and up to 2000 mg daily proceeded to randomization and started in Period 1.

• Period 1 (vildagliptin/metformin combination versus metformin): At Visit 3, patients were randomized 1:1 to one of the following study regimens:

  • Metformin up to 1000 mg bid plus vildagliptin 50mg bid or
  • Metformin up to 1000 mg bid plus matching placebo bid

The duration of Period 1 could differ between patients depending on the time when the second of two HbA1c measurements taken at two consecutive visits after randomisation confirmed HbA1c ≥ 7.0%.

• Period 2 (vildagliptin/metformin combination versus vildagliptin add-on to metformin): In the case of two consecutive HbA1c measurements ≥7.0% from two consecutive study visits during Period 1, patients who were randomised to the placebo arm in Period 1 received vildagliptin 50 mg bid. Patients who were randomised to the active vildagliptin 50 mg bid arm in Period 1 continued to receive vildagliptin 50 mg bid. All patients continued to take their metformin dose unchanged. Period 2 remained masked to the patient and both patients and investigators remained masked to the treatment allocation in Period 1.

If, during Period 2, therapy intensification was required in accordance with the local guidelines, the patient entered Period 3. The duration of Period 2 could differ between patients. End of Period 2 was considered when insulin treatment was initiated, or alternatively when the patient was discontinued because insulin treatment was not initiated in Period 3.

• Period 3 (insulin initiation): In Period 3, patients were to be initiated on open-label insulin. The study drug regimen continued unchanged and remained masked to the patient in Period 3 and both patients and investigators remained masked to the treatment allocation in Period 1.

Enrollment: 2,004 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Type 2 Diabetes Mellitus (T2DM) diagnosed ≤ 24 months ago
• glycosylated hemoglobin (HbA1c) ≥6.5% and ≤7.5% at Visit 1
• Treatment-naïve.
• Body mass index (BMI) ≥22 and ≤40 kg/m2 at Visit 1

Key Exclusion Criteria:

• Pregnant or nursing (lactating) women
• Fasting plasma glucose (FPG) ≥ 270 mg/dL (≥ 15.0 mmol/L)
• Previous or current participation in any vildagliptin clinical study.
• History of hypersensitivity to dipeptidyl peptidase-4 (DPP-4) inhibitors.
• Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
• Donation of blood or significant blood loss equaling to at least one unit of blood within the past 2 weeks of start of study or a blood transfusion within the past 12 weeks or planned regular transfusions during the study period.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,004 participants in 2 patient groups

Vilda 50mg bid + metformin

Active Comparator group

Description:

Metformin + vildagliptin

Treatment:

Drug: Metformin

Drug: vildagliptin

Placebo + metformin

Experimental group

Description:

Metformin + Placebo of vildagliptin

Treatment:

Drug: Metformin

Drug: Placebo of vildagliptin