Phase III Trial to Evaluate the Efficacy and Safety of LC15-0444 Compared With Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes

A Multicenter, Multinational, Randomized, Active-controlled, Parallel Group, Double-blind, Phase III Trial to Evaluate the Efficacy and Safety of LC15-0444 Compared With Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone

Double-blind, randomized, multicenter, multinational (South Korea and India), parallel group study The study was divided into three parts: part 1 was a screening period started with an initial 2 weeks of exercise/diet program; part 2 was a double-blind treatment period during which eligible patients were randomized to Sitagliptin 100 mg qd (once daily), LC15-0444 25 mg bid (twice daily), or LC15-0444 50 mg qd groups and received the assigned treatment for 24 weeks; part 3 was for those patients who completed part 1 & 2 and consented to receive another 28 weeks of treatment with LC15-0444 50 mg qd.

Screening tests were performed on the patients who had given the written informed consent. After 2-week exercise/diet program according to the generally recognized guideline, eligible patients were assigned one of three treatment groups with 1:1:1 ratio. During the total of 24-week treatment period of part 2, each patient visited the study site at Week 6, 12, 18, and 24. Completing double-blind treatment for 24 weeks, each patient was asked to provide consent to participate in the part 3 of the study where all the patients were to receive LC15-0444 50 mg once daily. During 28-week treatment period of the part 3, each patient visited the study

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: LC15-0444 25mg bid; Drug: LC15-0444 50mg qd; Drug: Sitagliptin 100mg qd

• Study Type: Interventional
• Enrollment (Actual): 425
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-062
    • LG Life Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with Type 2 Diabetes Mellitus
2. Adults between 18 and 75 years of age
3. Patients with HbA1c between 7% and 11%
4. Patients treated with metformin monotherapy for at least 12 weeks and treated with 1000 mg/day or higher dose of metformin for at least 4 weeks right before screening
5. Patients who signed on the consent form after informed on the object, method, and risks of the clinical study

Exclusion Criteria:

1. Patients with type 1 diabetes mellitus, gestational diabetes, or secondary diabetes
2. Patients who were taking or needed to take any drugs which may affect the control of blood glucose significantly (ex. glucocorticoids)
3. Patients who had experienced myocardial infarction, unstable angina or prior history of coronary artery bypass surgery within 6 months prior to screening, or patients with arrhythmia requiring treatment
4. Patients with NYHA class II-IV congestive heart failure
5. Patients with history of hepatic cirrhosis
6. Patients with renal failure or whose creatinine clearance was less than 60 ml/min
7. Patients with dysfunctional thyroid gland (with abnormal level of TSH)
8. Patients with ALT, AST or CPK exceeding 2.5 times of the upper limit of the normal range
9. Patients with BMI below 20 kg/m2 or exceeding 40 kg/m2
10. Patients with history of asthma or major skin allergy
11. Patients taking thyroid hormone, warfarin, dicoumarin or digoxin.
12. Patients with history of hypersensitivity to metformin or biguanides.
13. Patients with history of hypersensitivity to thiazolidinediones
14. Patients who took sodium channel blockers in the last 6 weeks prior to Visit 1.
15. Patients who were treated with insulin or glucagon-like peptide-1 (GLP-1) analogue or who took thiazolidinediones (Glitazone) in the last 6 months prior to Visit 1.
16. Patients with other reasons who the investigator decided not to be eligible for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LC15-0444 25 mg bid; LC15-0444 25 mg bid(twice daily)added on Metformin therapy	Drug: LC15-0444 25mg bid; Each patient was given 3 different bottles of study drugs that comprised of two morning bottles and one evening bottles. Each morning bottle contained LC15-0444 25 mg or 50 mg or Sitagliptin 100mg(depending on the randomized group) or its matching placebo while the evening bottle contained LC15-0444 25 mg or its matching placebo. Patient was instructed to take 1 tablet from each bottle at regular times in the morning and evening every day during the 24-week double-blind treatment period.
Experimental: LC15-0444 50 mg qd; LC15-0444 50 mg qd(once daily) added on Metformin therapy	Drug: LC15-0444 50mg qd; Each patient was given 3 different bottles of study drugs that comprised of two morning bottles and one evening bottles. Each morning bottle contained LC15-0444 25 mg or 50 mg or Sitagliptin 100mg(depending on the randomized group) or its matching placebo while the evening bottle contained LC15-0444 25 mg or its matching placebo. Patient was instructed to take 1 tablet from each bottle at regular times in the morning and evening every day during the 24-week double-blind treatment period.
Active Comparator: Sitagliptin 100mg qd; Sitagliptin 100 mg qd (once daily) added on the Metformin therapy	Drug: Sitagliptin 100mg qd; Each patient was given 3 different bottles of study drugs that comprised of two morning bottles and one evening bottles. Each morning bottle contained LC15-0444 25 mg or 50 mg or Sitagliptin 100mg(depending on the randomized group) or its matching placebo while the evening bottle contained LC15-0444 25 mg or its matching placebo. Patient was instructed to take 1 tablet from each bottle at regular times in the morning and evening every day during the 24-week double-blind treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of HbAlc	from baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c Responder Rate	responder rate of HbA1c <7%, <6.5% at week 24	at Week 24

Collaborators and Investigators

• Sponsor: LG Life Sciences
• Investigators: Principal Investigator: Sun Woo Kim, MD, PhD, Kangbuk Samsung Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: May 15, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (Estimate): May 18, 2012

Study Record Updates

• Last Update Posted (Estimate): May 18, 2012
• Last Update Submitted That Met QC Criteria: May 17, 2012
• Last Verified: May 1, 2012

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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: LG-DPCL006