A Study to Evaluate the Change in Weight After 24 Weeks Treatment With LIK066 in Obese or Overweight Adults

Study Overview
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Brief Summary
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This was a dose-finding study that evaluated the change in weight after 24 weeks treatment with 8 different doses of LIK066 compared to placebo in obese or overweight adults, followed by 24 weeks treatment with 2 doses of LIK066 and placebo.

Official Title
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A Randomized, Double-blind, Dose-finding Study to Evaluate the Change in Weight After 24 Weeks Treatment With 8 Doses of LIK066 Compared to Placebo in Obese or Overweight Adults, Followed by 24 Weeks Treatment With 2 Doses of LIK066 and Placebo

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Drug: LIK066
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent (BMI>=30) or (BMI>=27 with history of CV disease, hypertension, dyslipidemia, pre-diabetes or type 2 diabetes mellitus, sleep-apnea syndrome) willing to comply with life-style intervention and treatment during the full duration of the study (approximately 54 weeks) Exclusion Criteria: Hypersensitivity to any of the study medications Pregnancy or lactating women History of malignancies Use of pharmacologically active weight loss products Bariatric surgery Ketoacidosis, lactic acidosis, hyperosmolar coma in the 6 months before the screening visit. HbA1c >10% at the screening visit.

Ages Eligible for Study
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Minimum Age: 18 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 2.5mg qd (Epoch 3)<br>LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks. | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Placebo Comparator: Placebo (Epoch 3)<br>Matching placebo tablets for 24 weeks | Drug: Placebo<br>* Placebo<br>|
| Experimental: LIK066 10mg qd (Epoch 3)<br>LIK066 10mg qd (once daily) dosing frequency for 24 weeks | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 50mg qd (Epoch 3)<br>LIK066 50mg qd (once daily) dosing frequency for 24 weeks | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 150mg qd (Epoch 3)<br>LIK066 150mg qd (once daily) dosing frequency for 24 weeks | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 2.5mg bid (Epoch 3)<br>LIK066 2.5mg bid (once daily) dosing frequency for 24 weeks | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 5mg bid (Epoch 3)<br>LIK066 5mg bid (once daily) dosing frequency for 24 weeks | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 25mg bid (Epoch 3)<br>LIK066 25mg bid (once daily) dosing frequency for 24 weeks | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 50mg bid (Epoch 3)<br>LIK066 50mg bid dosing frequency for 24 weeks | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 qd/LIK066 25mg qd (Epoch 4)<br>Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: LIK066 bid/LIK066 35mg qd (Epoch 4)<br>Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Experimental: Placebo/LIK066 25mg qd (Epoch 4)<br>Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily | Drug: LIK066<br>* LIK066 will be supplied in different doses as tablets to be taken orally.<br>|
| Placebo Comparator: Placebo/Placebo (Epoch 4)<br>Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Body Weight at 24 Weeks | Dose-response relationship of two dose regimens of LIK066 as measured by the percent change from baseline in body weight relative to placebo after 24 weeks of treatment | Baseline, Week 24 (Epoch 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline | Baseline, Week 24 | 
| Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline for dysglycemic, normoglycemic, Type 2 Diabetes Mellitus (T2DM) | Baseline, Week 24 | 
| Percentage Change From Baseline on Waist Circumference | Waist circumference will be measured to the nearest 0.1cm in a standing position, at the end of a normal expiration, using a tape at the level of the iliac crest. | Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4) | 
| Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake). | Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4) | 
| Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | HbA1c will be measured from a blood sample obtained at indicated visits and will be analyzed at a central laboratory. | Baseline, Week 24 (Epoch 3), Week 24 to week 48 (Epoch 4) | 
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | At each study visit (baseline, week 24, Week 48), after the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP and DBP will be measured | Baseline, Week 24 (Epoch 3) Week 24 to Week 48 (Epoch 4) | 
| Change From Baseline in 24-hour Urinary Glucose Excretion | Urinary glucose excretion will be measured from 24-hour urinary collection at indicated visits and will be analyzed at a central laboratory. | Baseline, week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4) | 
| Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4) | Between -treatment analysis of percentage change from Week 24 in body weight (kg) at Week 48 (Epoch 4) | Between Week 24 and Week 48 (Epoch 4) | 
| Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Evaluation of 24-hour urinary calcium excretion after 24 week of treatment. | Baseline, Week 24 | 
| Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Evaluation of 24-hour urinary calcium after 48 weeks of treatment | Baseline, Week 24, Week 48 | 
| Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Evaluation of 24-hour urinary phosphorus excretion after 24 weeks of treatment | Week 24, Week 48 | 
| Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Evaluation of 24-hour urinary phosphorus excretion after 48 weeks of treatment | Week 24, Week 48 | 
| Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48 | Baseline, Week 24, Week 24 to Week 48 (Epoch 4) | 
| Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48 | Baseline to Week 24, Week 24 to Week 48 (Epoch 4) | 
| Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48 | Baseline to Week 24, Week 24 to Week 48 (Epoch 4) | 
| Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | Observe maximum plasma concentration following administration of LIK066 (Cmax) | Summary at Week 24 from qd or bid regimens | 
| Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | Time to reach the maximum concentration after administration of LIK066 (Tmax) | Summary at Week 24 for qd or bid regimens | 
| Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | Area under the plasma concentration-time curve from time zero time 't' where t is a defined time point after administration (AUC0-t) | Summary at Week 24 from qd or bid regimens (0-6h) | 
| Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | Last non-zero concentration area under the curve (AUClast) | Summary at Week 24 from qd or bid regimens | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Overweight