Study of Efficacy and Safety LMF237 in Patients With Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled With Vildagliptin Monotherapy

Study Overview
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Brief Summary
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The purpose of the study was to evaluate the efficacy and safety of LMF237 50/250 mg and 50/500 mg bid in Japanese patients with T2DM inadequately controlled with vildagliptin monotherapy. This study was conducted to support registration of the fixed-dose combination of vildagliptin and metformin for the treatment of T2DM in Japan.

Official Title
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A Multicenter, Double-Blind, Randomized, Parallel-Group Study to Compare the Effect of 14 Weeks Treatment With LMF237 Bid to Placebo in Patients With Type 2 Diabetes Inadequately Controlled With Vildagliptin 50 mg Bid Monotherapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: LMF237 50/250 mg
* Drug: LMF237 50/500 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes inadequately controlled with diet, exercise and oral anti-diabetic therapy HbA1c in the range of 7.0-10.0% Body mass index in the range of 20-35 kg/m^2 Exclusion Criteria: Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes Significant heart diseases Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LMF237 50/250 mg<br>Patients took LMF237 50/250 mg twice daily for 14 weeks | Drug: LMF237 50/250 mg<br>* Corresponds to vildagliptin 50 mg twice daily and metformin 250 mg twice daily<br>Drug: LMF237 50/500 mg<br>* Corresponds to vildagliptin 50 mg twice daily and metformin 500 mg twice daily<br>|
| Experimental: LMF237 50/500 mg<br>Patients took LMF237 50/500 mg (with a starting dose of LMF 237 50/250 mg for 2 weeks) twice daily for 14 weeks | Drug: LMF237 50/250 mg<br>* Corresponds to vildagliptin 50 mg twice daily and metformin 250 mg twice daily<br>|
| Placebo Comparator: Placebo<br>Patients took matching placebo of LMF237 (vildagliptin 50 mg) twice daily for 14 weeks | Drug: Placebo<br>* Matching placebo of LMF237 (contained vildagliptin 50 mg as active ingredient) twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 14 Weeks Between Treatment Groups | HbA1c was performed on a blood sample obtained and measured by High performance liquid chromatography (HPLC). HPCL was performed at a central laboratory. | Baseline to 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at 14 Weeks Within LMF237 Treatment Groups | HbA1c will be performed on a blood sample obtained and measured by HPLC. HPCL was performed at a central laboratory. | Baseline to 14 weeks | 
| Percentage of Patients Meeting Responder Rates in HbA1c | Responder rate was analyzed in categories: 1. Endpoint HbA1c ≤ 6.5% 2. Endpoint HbA1c < 7% 3. Endpoint HbA1c < 7% in patients with baseline HbA1c ≤ 8% 4. Endpoint HbA1c < 6.9% 5. HbA1c reduction from baseline at endpoint ≥ 1% 6. HbA1c reduction from baseline at endpoint ≥ 0.5%. Categories 1, 2, and 4 - 'n' includes only patients with baseline HbA1c > 6.5%, ≥ 7%, ≥ 6.9% and endpoint HbA1c measurement. Category 3, 'n' includes only patients with 7% ≤ baseline HbA1c ≤ 8% and endpoint HbA1c. Category 5 and 6, 'n' indicates number of patients with both baseline and endpoint HbA1c measurements. | Baseline, 14 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at 14 Weeks | FPG was performed on a blood sample obtained and analyzed at a central laboratory. | Baseline to 14 weeks | 
| Number of Patients With Adverse Events (Including Hypoglycemia), Serious Adverse Events and Death | The occurrence of adverse events were sought by non-directive questioning of the patient at each visit. Adverse events are defined as appearance or worsening of any undesirable symptom, sign (including an abnormal laboratory finding), or medical conditions. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards. | 14 weeks |