Effects of Carbohydrate in Diet and Supplements on the Gastrointestinal Tolerability of LIK066

Study Overview
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Brief Summary
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The purpose of this study was to determine if LIK066 taken with a meal containing low carbohydrate is associated with less diarrhea compared to a high carbohydrate meal and to assess the potential effects of supplements such as psyllium or calcium carbonate on alleviating diarrhea associated with LIK066.

Official Title
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A Randomized, Open Label, Two-part, Three-period, Cross Over Study to Investigate the Effects of Carbohydrate in Diet and to Evaluate Supplements on the Gastrointestinal Tolerability of LIK066 in Overweight or Obese Subjects

Conditions
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Obesity

Intervention / Treatment
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* Drug: LIK066
* Dietary Supplement: Carbohydrate 50%
* Dietary Supplement: Carbohydrate 25%
* Dietary Supplement: Carbohydrate 8%
* Dietary Supplement: Carbohydrate 0%
* Dietary Supplement: Psyllium
* Dietary Supplement: Calcium carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: obese and overweight, BMI 25-50, HbA1C <10% Exclusion Criteria: Preexisting, clinically significant cardiovascular, liver, renal, or GI disease that is considered unstable; pregnancy, Type 1 diabetes; Other protocol-defined inclusion/exclusion criteria may apply

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: LIK066 + P1: 50% CHO / P2: 25% CHO / P3: 0% CHO<br>Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 50% carbohydrate (CHO) Period 2 (Day 9-11): Daily dose of 50 mg LIK066 + 25% carbohydrate Period 3 (Day 17-19): Daily dose of 50 mg LIK066 + 0% carbohydrate | Drug: LIK066<br>* LIK066 50 mg tablets. Open-label, bulk, blister-pack.<br>Dietary Supplement: Carbohydrate 50%<br>* 50% carbohydrate in breakfast meal<br>Dietary Supplement: Carbohydrate 25%<br>* 25% carbohydrate in breakfast meal<br>Dietary Supplement: Carbohydrate 0%<br>* 0% carbohydrate in breakfast meal<br>|
| Experimental: Part A: LIK066 + P1: 25% CHO / P2: 0% CHO / P3: 50% CHO<br>Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 25% carbohydrate (CHO) Period 2 (Day 9-11): Daily dose of 50 mg LIK066 + 0% carbohydrate Period 3 (Day 17-19): Daily dose of 50 mg LIK066 + 50% carbohydrate | Drug: LIK066<br>* LIK066 50 mg tablets. Open-label, bulk, blister-pack.<br>Dietary Supplement: Carbohydrate 50%<br>* 50% carbohydrate in breakfast meal<br>Dietary Supplement: Carbohydrate 25%<br>* 25% carbohydrate in breakfast meal<br>Dietary Supplement: Carbohydrate 0%<br>* 0% carbohydrate in breakfast meal<br>|
| Experimental: Part A: LIK066 + P1: 0% CHO / P2: 50% CHO / P3: 25% CHO<br>Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 0% carbohydrate (CHO) Period 2 (Day 9-11): Daily dose of 50 mg LIK066 + 50% carbohydrate Period 3 (Day 17-19): Daily dose of 50 mg LIK066 + 25% carbohydrate | Drug: LIK066<br>* LIK066 50 mg tablets. Open-label, bulk, blister-pack.<br>Dietary Supplement: Carbohydrate 50%<br>* 50% carbohydrate in breakfast meal<br>Dietary Supplement: Carbohydrate 25%<br>* 25% carbohydrate in breakfast meal<br>Dietary Supplement: Carbohydrate 0%<br>* 0% carbohydrate in breakfast meal<br>|
| Experimental: Part A: LIK066 + P1: 8% CHO<br>Period 1 (Day 1-3): Daily dose of 50 mg LIK066 + 8% carbohydrate (CHO) PROTOCOL DEVIATION: subjects received 8% CHO in error and were discontinued after Period 1. | Drug: LIK066<br>* LIK066 50 mg tablets. Open-label, bulk, blister-pack.<br>Dietary Supplement: Carbohydrate 8%<br>* 8% carbohydrate in breakfast meal<br>|
| Experimental: Part B: LIK066 + 50% CHO + P1: NS / P2: PS / P3: CC<br>Period 1 (Day 1-3): Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS) Period 2 (Day 9-11): Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS) Period 3 (Day 17-19): Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC) | Drug: LIK066<br>* LIK066 50 mg tablets. Open-label, bulk, blister-pack.<br>Dietary Supplement: Carbohydrate 50%<br>* 50% carbohydrate in breakfast meal<br>Dietary Supplement: Psyllium<br>* Powder 6 grams<br>* Other names: MetaMucil®;Dietary Supplement: Calcium carbonate<br>* Liquid 1 gram (4 mL equivalent sugar free)<br>* Other names: Quality Value®;|
| Experimental: Part B: LIK066 + 50% CHO + P1: PS / P2: CC / P3: NS<br>Period 1 (Day 1-3): Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS) Period 2 (Day 9-11): Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC) Period 3 (Day 17-19): Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS) | Drug: LIK066<br>* LIK066 50 mg tablets. Open-label, bulk, blister-pack.<br>Dietary Supplement: Carbohydrate 50%<br>* 50% carbohydrate in breakfast meal<br>Dietary Supplement: Psyllium<br>* Powder 6 grams<br>* Other names: MetaMucil®;Dietary Supplement: Calcium carbonate<br>* Liquid 1 gram (4 mL equivalent sugar free)<br>* Other names: Quality Value®;|
| Experimental: Part B: LIK066 + 50% CHO + P1: CC / P2: NS / P3: PS<br>Period 1 (Day 1-3): Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC) Period 2 (Day 9-11): Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS) Period 3 (Day 17-19): Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS) | Drug: LIK066<br>* LIK066 50 mg tablets. Open-label, bulk, blister-pack.<br>Dietary Supplement: Carbohydrate 50%<br>* 50% carbohydrate in breakfast meal<br>Dietary Supplement: Psyllium<br>* Powder 6 grams<br>* Other names: MetaMucil®;Dietary Supplement: Calcium carbonate<br>* Liquid 1 gram (4 mL equivalent sugar free)<br>* Other names: Quality Value®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Episodes of Diarrhea (Part A and Part B) | Episodes of diarrhea is defined as the total number of stools with a Bristol Stool Chart (BSC) Score of 6 or 7 on day 3 of each treatment period. BSC is frequently used as a measure of consistency, and a score of 6 or 7 (pourable or watery stool) is considered abnormal. | 24 hours on Day 3 of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | Episodes of diarrhea is defined as the total number of stools with a Bristol Stool Chart (BSC) Score of 6 or 7 on days 1 to 3 of each treatment period. BSC is frequently used as a measure of consistency, and a score of 6 or 7 (pourable or watery stool) is considered abnormal. | Day 1 to 3 of each treatment period | 
| Average Consistency With Bristol Stool Chart (Part A and Part B) | BSC is frequently used as a measure of consistency, ranging from score 1 (hard lumps) to 7 (watery stool). | 24 hours on Day 3 of each treatment period | 
| Average Stool pH (Part A and Part B) | Average PH of Stool at day 3 | 24 hours on Day 3 of each treatment period | 
| Average Stool Weight (Part A and Part B) | 24 hour average stool weight on day 3 | 24 hours on Day 3 of each treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, overweight, body mass index, BMI, diarrhea