A Dose-finding Study to Evaluate the Change in Weight After Treatment With LIK066 in Japanese Patients With Obesity

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy, tolerability and safety of LIK066 to support dose selection for Phase 3 development in Japanese adults with obesity disease.

Official Title
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A Randomized, Double-blind, Dose-finding Study to Evaluate the Change in Weight After 12 Weeks Treatment With 4 Doses of LIK066 Compared to Placebo in Japanese Patients With Obesity Disease

Conditions
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Obesity

Intervention / Treatment
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* Drug: LIK066
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with obesity disease and inadequately controlled body weight with diet and/or exercise BMI ≥ 25 kg/m^2 combined with at least two obesity-related comorbidities, or BMI ≥ 35 kg/m^2 at least one obesity-related comorbidity Patients with FPG ≥ 110 mg/dL and/or 5.6% ≤ HbA1c ≤ 10.0%, or T2DM with HbA1c ≤ 10.0% Waist circumference at umbilical level ≥ 85 cm for male, ≥ 90 cm for female Visceral fat area ≥ 100 cm^2 Agreement to comply with the study-required life-style intervention and treatment during the full duration of the study Exclusion Criteria: Pregnancy or lactating women Use of pharmacologically active weight-loss medications Bariatric surgery Ketoacidosis, lactic acidosis, hyperosmolar coma Symptomatic genital ingection or urinary tract infection in the 4 weeks prior to screening Gastro-intestinal (GI) disorders associated with chronic diarrhea Congestive heart failure, New York Heart Association (NYHA) class III or IV

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LIK066 2.5 mg<br>Eligible patients randomized to this arm will receive LIK066 2.5 mg orally daily for 12 weeks. | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally daily.<br>|
| Experimental: LIK066 10 mg<br>Eligible patients randomized to this arm will receive LIK066 10 mg orally daily for 12 weeks. | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally daily.<br>|
| Experimental: LIK066 25 mg<br>Eligible patients randomized to this arm will receive LIK066 25 mg orally daily for 12 weeks. | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally daily.<br>|
| Experimental: LIK066 50 mg<br>Eligible patients randomized to this arm will receive LIK066 50 mg orally daily for 12 weeks. | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally daily.<br>|
| Placebo Comparator: Placebo<br>Eligible patient randomized to this arm will receive LIK066 matching placebo orally daily for 12 weeks. | Drug: Placebo<br>* Placebo will be supplied as tablets to be taken daily orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Body Weight at Week 12 | The dose-response relationship of LIK066 as measured by percent change from baseline in body weight relative to placebo after 12 weeks of treatment. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rates According to Percentage Decrease in Body Weight From Baseline to Week 12 | The responder rates according to percentage decrease in body weight either ≥ 3%, ≥ 5% or ≥ 10%, from baseline at Week 12, for the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 No Statistical Analysis for >=5% and >=10% was not calculated due to division by zero | Baseline, Week 12 | 
| Percentage Change From Baseline in Body Weight at Week 12 in Dysglycemic Participants and Participants With Type 2 Diabetes Mellitus (T2DM) | The dose-response relationship for weight loss in dysglycemic participants and participants with T2DM. Percentage change from baseline in body weight at Week 12. | Baseline, Week 12 | 
| Change From Baseline at Week 12 on Waist Circumference at Umbilical Level | Waist circumference will be measured to the nearest 0.1 cm in a standing position, at the end of a normal expiration, using a tape at the level of umbilicus. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percentage Change From Baseline at Week 12 on Hemoglobin A1c (HbA1c) | HbA1c will be measured from a blood sample obtained and analyzed at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Change From Baseline at Week 12 on Fasting Plasma Glucose (FPG) | FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake) at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Change From Baseline at Week 12 on Systolic Blood Pressure (SBP) | After the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP will be measured three times using the automatic BP monitor and an appropriate size cuff. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Change From Baseline at Week 12 on Diastolic Blood Pressure (DBP) | After the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, DBP will be measured three times using the automatic BP monitor and an appropriate size cuff. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Triglycerides (TG) | Fasting lipid profile (Triglycerides (TG)), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Total Cholesterol | Fasting lipid profile (total cholesterol), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - High Density Lipoprotein (HDL) | Fasting lipid profile (HDL), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Low Density Lipoprotein (LDL) | Fasting lipid profile (LDL), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percent Change From Baseline at Week 12 on High Sensitive C-reactive Protein (hsCRP) | High sensitivity CRP will be measured from a blood sample and analyzed at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Change From Baseline in Uric Acid at Week 12 | Uric acid will be measured from a blood sample and analyzed at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Change From Baseline on Urine Albumin at Week 12 | Urine albumin will be measured from urine sample and analyzed at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Change From Baseline on Urine Albumin to Creatinine Ratio at Week 12 | Urine albumin to creatinine ratio will be measured from urine sample and analyzed at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percent Change From Baseline on Visceral Fat Area (VFA) at Week 12 | VFA by CT scan will be measured at visits and evaluated centrally. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Percent Change From Baseline on Subcutaneous Fat Area (SFA) at Week 12 | SFA by CT scan will be measured at visits and evaluated centrally. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 | Baseline, Week 12 | 
| Pharmacokinetics - Plasma Trough Concentrations of LIK066 | Plasma trough concentrations of LIK066 were measured at Week 12 after daily administrations of LIK066 (2.5, 10, 25 and 50 mg). | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity disease, Over weight, T2DM, interventional study, Weight loss