Obesity
Conditions
Keywords
obesity, overweight, body mass index, BMI, diarrhea
Brief summary
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.
Interventions
DRUGLIK066
LIK066 50 mg tablets. Open-label, bulk, blister-pack.
DIETARY_SUPPLEMENTCarbohydrate 50%
50% carbohydrate in breakfast meal
DIETARY_SUPPLEMENTCarbohydrate 25%
25% carbohydrate in breakfast meal
DIETARY_SUPPLEMENTCarbohydrate 8%
8% carbohydrate in breakfast meal
DIETARY_SUPPLEMENTCarbohydrate 0%
0% carbohydrate in breakfast meal
DIETARY_SUPPLEMENTPsyllium
Powder 6 grams
DIETARY_SUPPLEMENTCalcium carbonate
Liquid 1 gram (4 mL equivalent sugar free)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Episodes of Diarrhea (Part A and Part B) | 24 hours on Day 3 of each treatment period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | Day 1 to 3 of each treatment period | 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. |
| Average Consistency With Bristol Stool Chart (Part A and Part B) | 24 hours on Day 3 of each treatment period | BSC is frequently used as a measure of consistency, ranging from score 1 (hard lumps) to 7 (watery stool). |
| Average Stool pH (Part A and Part B) | 24 hours on Day 3 of each treatment period | Average PH of Stool at day 3 |
| Average Stool Weight (Part A and Part B) | 24 hours on Day 3 of each treatment period | 24 hour average stool weight on day 3 |
Countries
United States
Participant flow
Recruitment details
A total of 116 subjects were screened and 54 subjects were enrolled and randomized, with 48 completing the study. 6 subjects in Part A were discontinued due to a protocol deviation after day 3 dosing (the protein drink provided to subjects was incorrect and included 8% carbohydrate).
Participants by arm
| Arm | Count |
|---|---|
| Part A: LIK066 + P1: 50% CHO / P2: 25% CHO / P3: 0% CHO 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 | 8 |
| Part A: LIK066 + P1: 25% CHO / P2: 0% CHO / P3: 50% CHO 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 | 8 |
| Part A: LIK066 + P1: 0% CHO / P2: 50% CHO / P3: 25% CHO 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 | 8 |
| Part A: LIK066 + P1: 8% CHO 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. | 6 |
| Part B: LIK066 + 50% CHO + P1: NS / P2: PS / P3: CC 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) | 8 |
| Part B: LIK066 + 50% CHO + P1: PS / P2: CC / P3: NS 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) | 8 |
| Part B: LIK066 + 50% CHO + P1: CC / P2: NS / P3: PS 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) | 8 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 0 | 6 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: LIK066 + P1: 50% CHO / P2: 25% CHO / P3: 0% CHO | Part A: LIK066 + P1: 25% CHO / P2: 0% CHO / P3: 50% CHO | Part A: LIK066 + P1: 0% CHO / P2: 50% CHO / P3: 25% CHO | Part A: LIK066 + P1: 8% CHO | Part B: LIK066 + 50% CHO + P1: NS / P2: PS / P3: CC | Part B: LIK066 + 50% CHO + P1: PS / P2: CC / P3: NS | Part B: LIK066 + 50% CHO + P1: CC / P2: NS / P3: PS | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 32.1 Years | 45.5 Years | 43.9 Years | 53.3 Years | 43.8 Years | 50.1 Years | 43.3 Years | 44.3 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 7 Participants | 6 Participants | 6 Participants | 7 Participants | 8 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 6 Participants | 5 Participants | 8 Participants | 5 Participants | 4 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 6 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 21 / 24 | 19 / 24 | 19 / 24 | 5 / 6 | 21 / 24 | 19 / 24 | 22 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 6 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
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.
Time frame: 24 hours on Day 3 of each treatment period
Population: PD Analysis Set. All subjects with any available pharmacodynamic (PD) data and no major protocol deviations with impact on PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: LIK066 + 50% CHO | Number of Episodes of Diarrhea (Part A and Part B) | 1.67 Number of stools | Standard Deviation 1.74 |
| Part A: LIK066 + 25% CHO | Number of Episodes of Diarrhea (Part A and Part B) | 1.25 Number of stools | Standard Deviation 1.42 |
| Part A: LIK066 + 0% CHO | Number of Episodes of Diarrhea (Part A and Part B) | 0.38 Number of stools | Standard Deviation 0.71 |
| Part B: LIK066 + 50% CHO + NS | Number of Episodes of Diarrhea (Part A and Part B) | 1.88 Number of stools | Standard Deviation 1.51 |
| Part B: LIK066 + 50% CHO + PS | Number of Episodes of Diarrhea (Part A and Part B) | 1.46 Number of stools | Standard Deviation 1.41 |
| Part B: LIK066 + 50% CHO CC | Number of Episodes of Diarrhea (Part A and Part B) | 1.46 Number of stools | Standard Deviation 1.67 |
Comparison: Day 3p-value: 0.20280% CI: [0.5, 1]Mixed Models Analysis
Comparison: Day 3p-value: <0.00180% CI: [0.14, 0.32]Mixed Models Analysis
Comparison: Day 3p-value: <0.00180% CI: [0.19, 0.46]Mixed Models Analysis
Comparison: Day 3p-value: 0.27580% CI: [0.6, 1.04]Mixed Models Analysis
Comparison: Day 3p-value: 0.23480% CI: [0.59, 1.02]Mixed Models Analysis
Comparison: Day 3p-value: 0.92180% CI: [0.73, 1.3]Mixed Models Analysis
Secondary
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).
Time frame: 24 hours on Day 3 of each treatment period
Population: PD Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: LIK066 + 50% CHO | Average Consistency With Bristol Stool Chart (Part A and Part B) | 5.45 score | Standard Deviation 1.24 |
| Part A: LIK066 + 25% CHO | Average Consistency With Bristol Stool Chart (Part A and Part B) | 5.42 score | Standard Deviation 1.42 |
| Part A: LIK066 + 0% CHO | Average Consistency With Bristol Stool Chart (Part A and Part B) | 4.71 score | Standard Deviation 1.45 |
| Part B: LIK066 + 50% CHO + NS | Average Consistency With Bristol Stool Chart (Part A and Part B) | 5.81 score | Standard Deviation 1.07 |
| Part B: LIK066 + 50% CHO + PS | Average Consistency With Bristol Stool Chart (Part A and Part B) | 5.52 score | Standard Deviation 0.99 |
| Part B: LIK066 + 50% CHO CC | Average Consistency With Bristol Stool Chart (Part A and Part B) | 5.62 score | Standard Deviation 1.02 |
p-value: 0.42680% CI: [-0.56, 0.13]Mixed Models Analysis
p-value: 0.00180% CI: [-1.46, -0.67]Mixed Models Analysis
p-value: 0.00980% CI: [-1.25, -0.45]Mixed Models Analysis
p-value: 0.13580% CI: [-0.68, -0.05]Mixed Models Analysis
p-value: 0.43680% CI: [-0.5, 0.12]Mixed Models Analysis
p-value: 0.45280% CI: [-0.13, 0.49]Mixed Models Analysis
Secondary
Average Stool pH (Part A and Part B)
Average PH of Stool at day 3
Time frame: 24 hours on Day 3 of each treatment period
Population: PD Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: LIK066 + 50% CHO | Average Stool pH (Part A and Part B) | 6.35 pH | Standard Deviation 0.44 |
| Part A: LIK066 + 25% CHO | Average Stool pH (Part A and Part B) | 6.50 pH | Standard Deviation 0.59 |
| Part A: LIK066 + 0% CHO | Average Stool pH (Part A and Part B) | 6.29 pH | Standard Deviation 0.23 |
| Part B: LIK066 + 50% CHO + NS | Average Stool pH (Part A and Part B) | 6.52 pH | Standard Deviation 0.59 |
| Part B: LIK066 + 50% CHO + PS | Average Stool pH (Part A and Part B) | 6.79 pH | Standard Deviation 0.67 |
| Part B: LIK066 + 50% CHO CC | Average Stool pH (Part A and Part B) | 6.66 pH | Standard Deviation 0.5 |
Secondary
Average Stool Weight (Part A and Part B)
24 hour average stool weight on day 3
Time frame: 24 hours on Day 3 of each treatment period
Population: PD Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: LIK066 + 50% CHO | Average Stool Weight (Part A and Part B) | 136.5 gram | Standard Deviation 88.99 |
| Part A: LIK066 + 25% CHO | Average Stool Weight (Part A and Part B) | 154.5 gram | Standard Deviation 87.11 |
| Part A: LIK066 + 0% CHO | Average Stool Weight (Part A and Part B) | 116.7 gram | Standard Deviation 65.57 |
| Part B: LIK066 + 50% CHO + NS | Average Stool Weight (Part A and Part B) | 145.5 gram | Standard Deviation 75.21 |
| Part B: LIK066 + 50% CHO + PS | Average Stool Weight (Part A and Part B) | 177.1 gram | Standard Deviation 138.1 |
| Part B: LIK066 + 50% CHO CC | Average Stool Weight (Part A and Part B) | 164.3 gram | Standard Deviation 108.5 |
Secondary
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.
Time frame: Day 1 to 3 of each treatment period
Population: PD Analysis Set. All subjects with any available pharmacodynamic (PD) data and no major protocol deviations with impact on PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: LIK066 + 50% CHO | Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | 3.96 Number of stools | Standard Deviation 3.01 |
| Part A: LIK066 + 25% CHO | Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | 2.83 Number of stools | Standard Deviation 2.97 |
| Part A: LIK066 + 0% CHO | Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | 1.50 Number of stools | Standard Deviation 2.02 |
| Part B: LIK066 + 50% CHO + NS | Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | 4.42 Number of stools | Standard Deviation 3.41 |
| Part B: LIK066 + 50% CHO + PS | Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | 3.46 Number of stools | Standard Deviation 3.24 |
| Part B: LIK066 + 50% CHO CC | Three-day Total Number of Episodes of Diarrhea (Part A and Part B) | 4.00 Number of stools | Standard Deviation 3.11 |
p-value: 0.0480% CI: [0.54, 0.86]Mixed Models Analysis
p-value: <0.00180% CI: [0.28, 0.49]Mixed Models Analysis
p-value: 0.00880% CI: [0.41, 0.72]Mixed Models Analysis
p-value: 0.14180% CI: [0.65, 0.97]Mixed Models Analysis
p-value: 0.5180% CI: [0.74, 1.1]Mixed Models Analysis
p-value: 0.40180% CI: [0.93, 1.41]Mixed Models Analysis