Study of Efficacy and Safety LMF237 in Patients With Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled With Vildagliptin Monotherapy (CLMF237A1303)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: LMF237 50/250 mg; Drug: LMF237 50/500 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka
    • Chikushino-city, Fukuoka, Japan, 818-0083
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 810-0014
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 819-0006
      • Novartis Investigative Site
    • Iizuka-city, Fukuoka, Japan, 820-8505
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 800-0296
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 807-0857
      • Novartis Investigative Site
  • Ibaraki
    • Koga-city, Ibaraki, Japan, 306-0232
      • Novartis Investigative Site
  • Kanagawa
    • Kawasaki-city, Kanagawa, Japan, 210-0852
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 231-0023
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 221-0802
      • Novartis Investigative Site
  • Kumamoto
    • Yatsushiro-city, Kumamoto, Japan, 866-8660
      • Novartis Investigative Site
    • Yatsushiro-city, Kumamoto, Japan, 866-8533
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 615-0035
      • Novartis Investigative Site
    • Kyoto-city, Kyoto, Japan, 607-8062
      • Novartis Investigative Site
  • Osaka
    • Sakai-city, Osaka, Japan, 590-0064
      • Novartis Investigative Site
    • Takatsuki-city, Osaka, Japan, 569-1096
      • Novartis Investigative Site
  • Saitama
    • Ageo-city, Saitama, Japan, 362-8588
      • Novartis Investigative Site
    • Tokorozawa-city, Saitama, Japan, 359-1161
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-0031
      • Novartis Investigative Site
    • Edogawa-ku, Tokyo, Japan, 134-0084
      • Novartis Investigative Site
    • Hachioji, Tokyo, Japan, 192-0046
      • Novartis Investigative Site
    • Hachioji-city, Tokyo, Japan, 192-0918
      • Novartis Investigative Site
    • Katsushika-ku, Tokyo, Japan, 124-0024
      • Novartis Investigative Site
    • Kiyose-city, Tokyo, Japan, 204-0021
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-7390
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 108-0075
      • Novartis Investigative Site
    • Nerima-ku, Tokyo, Japan, 177-0051
      • Novartis Investigative Site
    • Shibuya-ku, Tokyo, Japan, 150-0002
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 141-0032
      • Novartis Investigative Site
    • Toshima-ku, Tokyo, Japan, 171-0021
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LMF237 50/250 mg; Patients took LMF237 50/250 mg twice daily for 14 weeks	Drug: LMF237 50/250 mg; Corresponds to vildagliptin 50 mg twice daily and metformin 250 mg twice daily; Drug: LMF237 50/500 mg; Corresponds to vildagliptin 50 mg twice daily and metformin 500 mg twice daily
EXPERIMENTAL: LMF237 50/500 mg; 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; Corresponds to vildagliptin 50 mg twice daily and metformin 250 mg twice daily
PLACEBO_COMPARATOR: Placebo; Patients took matching placebo of LMF237 (vildagliptin 50 mg) twice daily for 14 weeks	Drug: Placebo; Matching placebo of LMF237 (contained vildagliptin 50 mg as active ingredient) twice daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: March 12, 2013
• First Submitted That Met QC Criteria: March 12, 2013
• First Posted (ESTIMATE): March 14, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): February 23, 2015
• Last Update Submitted That Met QC Criteria: February 4, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CLMF237A1303