Effect of LIK066 on Body Weight in Patients With Elevated Body Mass Index

Study Overview
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Brief Summary
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A 12-week study to assess LIK066 effect on body weight in diabetics, prediabetics and normoglycemic patients with elevated body mass index (BMI)

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Group, 2-part Study Investigating the Effect of LIK066 on Body Weight in Dysglycemic (Prediabetes or Type 2 Diabetes) and Normoglycemic Patients With Elevated Body Mass Index

Conditions
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Elevated Body Mass Index

Intervention / Treatment
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* Drug: LIK066
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects with stable health condition as determined by past medical history, physical examination, electrocardiogram, and laboratory tests at screening. Patients with dysglycemia are patients with: Fasting plasma glucose >100mg/dL (5.6 mmol/L), or HbA1c > 5.7% and < 10% at screening. Fasting plasma glucose ≤250mg/dL (13.9 mmol/L) at screening. If treated with antidiabetic medications (other than prohibited medications), patients must be on a stable dose for 12 weeks prior to randomization and maintain the dose until the end of the study. Subjects must have a body mass index (BMI) within the range of 35 - 50 kg/m2 at screening, with stable body weight (± 5 kg) within 3 months prior to screening Key Exclusion Criteria: Pre-existing, clinically significant gastrointestinal, liver, cardiovascular, renal or other chronic medical condition which is considered serious or unstable, other than stable cardiovascular disease, treated hypertension, dyslipidemia or other stable chronic disorders Clinically significant GI disorder related to malabsorption or that may affect drug or glucose absorption or history of significant gastrointestinal surgery that could affect intestinal glucose absorption Enrollment in a diet, weight loss or exercise programs with the specific intent of losing weight, within 3 months prior to randomization, or clinical diagnosis of any eating disorder Pregnant or nursing (lactating) women, and women of child-bearing potential

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: LIK066 150 mg once daily (qd)<br>LIK066 150 mg qd within 15 minutes before starting lunch | Drug: LIK066<br>* LIK066 25 mg tablets<br>|
| Placebo Comparator: Part 1: Placebo once daily<br>Matching placebo tablets of LCZ696 150 mg within 15 minutes before starting lunch. | Drug: LIK066<br>* LIK066 25 mg tablets<br>|
| Experimental: Part 2: LIK066 75 mg twice daily (bid)<br>LIK066 75 mg bid before breakfast and dinner | Drug: Placebo<br>* Matching placebo tablets<br>|
| Experimental: Part 2: LIK066 50 mg three times daily (tid)<br>LIK066 50 mg tid before all 3 meals; | Drug: Placebo<br>* Matching placebo tablets<br>|
| Placebo Comparator: Part 2: Placebo three times daily<br>Matching placebo tablets tid before meals. | Drug: LIK066<br>* LIK066 25 mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percent Change in Body Weight From Baseline to Week 12 | Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is Day -1 in Part 1. Percent change is calculated as [(post baseline- Baseline) /Baseline] * 100. A longitudinal mixed effects model for percent change in body weight was used. The model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by- time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, and the treatment-by-time-by-glycemic status interaction, and Baseline body weight as a covariate. | Baseline, Week 12 (Day 85) | 
| Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | This endpoint reports patients with at least one AE (any AE), serious AE and death. | 12 weeks | 
| Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) | Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Part 1: Baseline is defined as Day -1. Part 2: Baseline is defined as Day 1 predose. Percent change is calculated as [(post baseline- Baseline) /Baseline] * 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate. | Baseline, Week 2 (Day 14) | 
| Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | This endpoint reports patients with at least one AE (any AE), serious AE and death | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms | Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is defined as Day 1 predose. Percent change is calculated as [(post baseline- Baseline) /Baseline] * 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate. | Baseline, Week 2 | 
| Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study | Blood samples were collected at predose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h postdose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. | Day 84 | 
| Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. | Day 84 | 
| Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. | Day 84 | 
| Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. | Day 84 | 
| The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. | Day 84 | 
| The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. | Day 84 | 
| Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Cmax at steady state (Cmax, ss) | Day 1, Day 14 | 
| Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Tmax at steady state (Tmax, ss) | Day 1, Day 14 | 
| Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUClast at steady state (AUClast, ss) | Day 1, Day 14 | 
| Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUCtau at steady state (AUCtau, ss) | Day 1, Day 14 | 
| The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports CLss/F at steady state (CLss/F, ss) | Day 1, Day 14 | 
| The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Vz/F at steady state (Vz/F, ss) | Day 1, Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dysglycemic, normoglycemic, prediabetes, type 2 diabetes mellitus