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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03198767
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 7
• Actual Duration (Months): 2.5
• Patients Per Site Per Month: 21.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	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	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: Jun 21, 2017
• Actual Primary Completion Date: Sep 4, 2017
• Actual Study Completion Date: Sep 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: LIK066; LIK066 50 mg tablets. Open-label, bulk, blister-pack.; Dietary Supplement: Carbohydrate 50%; 50% carbohydrate in breakfast meal; Dietary Supplement: Carbohydrate 25%; 25% carbohydrate in breakfast meal; Dietary Supplement: Carbohydrate 0%; 0% carbohydrate in breakfast meal
Experimental: 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	Drug: LIK066; LIK066 50 mg tablets. Open-label, bulk, blister-pack.; Dietary Supplement: Carbohydrate 50%; 50% carbohydrate in breakfast meal; Dietary Supplement: Carbohydrate 25%; 25% carbohydrate in breakfast meal; Dietary Supplement: Carbohydrate 0%; 0% carbohydrate in breakfast meal
Experimental: 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	Drug: LIK066; LIK066 50 mg tablets. Open-label, bulk, blister-pack.; Dietary Supplement: Carbohydrate 50%; 50% carbohydrate in breakfast meal; Dietary Supplement: Carbohydrate 25%; 25% carbohydrate in breakfast meal; Dietary Supplement: Carbohydrate 0%; 0% carbohydrate in breakfast meal
Experimental: 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.	Drug: LIK066; LIK066 50 mg tablets. Open-label, bulk, blister-pack.; Dietary Supplement: Carbohydrate 8%; 8% carbohydrate in breakfast meal
Experimental: 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)	Drug: LIK066; LIK066 50 mg tablets. Open-label, bulk, blister-pack.; Dietary Supplement: Carbohydrate 50%; 50% carbohydrate in breakfast meal; Dietary Supplement: Psyllium; Powder 6 grams; Other Names: MetaMucil® ; Dietary Supplement: Calcium carbonate; Liquid 1 gram (4 mL equivalent sugar free); Other Names: Quality Value®
Experimental: 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)	Drug: LIK066; LIK066 50 mg tablets. Open-label, bulk, blister-pack.; Dietary Supplement: Carbohydrate 50%; 50% carbohydrate in breakfast meal; Dietary Supplement: Psyllium; Powder 6 grams; Other Names: MetaMucil® ; Dietary Supplement: Calcium carbonate; Liquid 1 gram (4 mL equivalent sugar free); Other Names: Quality Value®
Experimental: 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)	Drug: LIK066; LIK066 50 mg tablets. Open-label, bulk, blister-pack.; Dietary Supplement: Carbohydrate 50%; 50% carbohydrate in breakfast meal; Dietary Supplement: Psyllium; Powder 6 grams; Other Names: MetaMucil® ; Dietary Supplement: Calcium carbonate; Liquid 1 gram (4 mL equivalent sugar free); Other Names: Quality Value®

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

3. Average Stool pH (Part A and Part B) [24 hours on Day 3 of each treatment period]

   Average PH of Stool at day 3

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Lincoln	Nebraska	United States	68502

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 8, 2017
• Statistical Analysis Plan - Sep 27, 2017

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03198767
• Other Study ID Numbers: CLIK066B2203
• First Posted: Jun 26, 2017
• Last Update Posted: Jan 5, 2021
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: obesity; overweight; body mass index; BMI; diarrhea
• Additional relevant MeSH terms: Obesity; Licogliflozin; Calcium Carbonate; Psyllium; Calcium

Study Results

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).

Arm/Group Title	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
Arm/Group Description	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	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	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	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.	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)	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)	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)
Period Title: Overall Study
STARTED	8	8	8	6	8	8	8
COMPLETED	8	8	8	0	8	8	8
NOT COMPLETED	0	0	0	6	0	0	0

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	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	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	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	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.	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)	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)	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)	Total of all reporting groups
Overall Participants	8	8	8	6	8	8	8	54
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	32.1	45.5	43.9	53.3	43.8	50.1	43.3	44.3
Sex: Female, Male (Count of Participants)
Female	5 62.5%	2 25%	2 25%	1 16.7%	0 0%	3 37.5%	4 50%	17 31.5%
Male	3 37.5%	6 75%	6 75%	5 83.3%	8 100%	5 62.5%	4 50%	37 68.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 37.5%	1 12.5%	1 12.5%	0 0%	2 25%	1 12.5%	0 0%	8 14.8%
Not Hispanic or Latino	5 62.5%	7 87.5%	7 87.5%	6 100%	6 75%	7 87.5%	8 100%	46 85.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Episodes of Diarrhea (Part A and Part B)
Description	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

Outcome Measure Data

Analysis Population Description

PD Analysis Set. All subjects with any available pharmacodynamic (PD) data and no major protocol deviations with impact on PD data.

Arm/Group Title	Part A: LIK066 + 50% CHO	Part A: LIK066 + 25% CHO	Part A: LIK066 + 0% CHO	Part B: LIK066 + 50% CHO + NS	Part B: LIK066 + 50% CHO + PS	Part B: LIK066 + 50% CHO CC
Arm/Group Description	Part A: LIK066 + 50% carbohydrate CHO	Part A: LIK066 + 25% carbohydrate CHO	Part A: LIK066 + 0% carbohydrate CHO	Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS)	Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS)	Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC)
Measure Participants	24	24	24	24	24	24
Mean (Standard Deviation) [Number of stools]	1.67 (1.74)	1.25 (1.42)	0.38 (0.71)	1.88 (1.51)	1.46 (1.41)	1.46 (1.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 50% CHO, Part A: LIK066 + 25% CHO
	Comments	Day 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.202
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 80%; 0.50 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 50% CHO, Part A: LIK066 + 0% CHO
	Comments	Day 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 80%; 0.14 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 25% CHO, Part A: LIK066 + 0% CHO
	Comments	Day 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 80%; 0.19 to 0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + NS, Part B: LIK066 + 50% CHO + PS
	Comments	Day 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.275
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 80%; 0.60 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + NS, Part B: LIK066 + 50% CHO CC
	Comments	Day 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.234
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 80%; 0.59 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + PS, Part B: LIK066 + 50% CHO CC
	Comments	Day 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.921
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 80%; 0.73 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Three-day Total Number of Episodes of Diarrhea (Part A and Part B)
Description	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

Outcome Measure Data

Analysis Population Description

PD Analysis Set. All subjects with any available pharmacodynamic (PD) data and no major protocol deviations with impact on PD data.

Arm/Group Title	Part A: LIK066 + 50% CHO	Part A: LIK066 + 25% CHO	Part A: LIK066 + 0% CHO	Part B: LIK066 + 50% CHO + NS	Part B: LIK066 + 50% CHO + PS	Part B: LIK066 + 50% CHO CC
Arm/Group Description	Part A: LIK066 + 50% carbohydrate CHO	Part A: LIK066 + 25% carbohydrate CHO	Part A: LIK066 + 0% carbohydrate CHO	Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS)	Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS)	Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC)
Measure Participants	24	24	24	24	24	24
Mean (Standard Deviation) [Number of stools]	3.96 (3.01)	2.83 (2.97)	1.50 (2.02)	4.42 (3.41)	3.46 (3.24)	4.00 (3.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 50% CHO, Part A: LIK066 + 25% CHO
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.040
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 80%; 0.54 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 50% CHO, Part A: LIK066 + 0% CHO
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 80%; 0.28 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 25% CHO, Part A: LIK066 + 0% CHO
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 80%; 0.41 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + NS, Part B: LIK066 + 50% CHO + PS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.141
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 80%; 0.65 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + NS, Part B: LIK066 + 50% CHO CC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.510
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 80%; 0.74 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + PS, Part B: LIK066 + 50% CHO CC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.401
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio of number of events
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 80%; 0.93 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Average Consistency With Bristol Stool Chart (Part A and Part B)
Description	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

Outcome Measure Data

Analysis Population Description

PD Analysis Set.

Arm/Group Title	Part A: LIK066 + 50% CHO	Part A: LIK066 + 25% CHO	Part A: LIK066 + 0% CHO	Part B: LIK066 + 50% CHO + NS	Part B: LIK066 + 50% CHO + PS	Part B: LIK066 + 50% CHO CC
Arm/Group Description	Part A: LIK066 + 50% carbohydrate CHO	Part A: LIK066 + 25% carbohydrate CHO	Part A: LIK066 + 0% carbohydrate CHO	Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS)	Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS)	Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC)
Measure Participants	24	24	24	24	24	24
Mean (Standard Deviation) [score]	5.45 (1.24)	5.42 (1.42)	4.71 (1.45)	5.81 (1.07)	5.52 (0.99)	5.62 (1.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 50% CHO, Part A: LIK066 + 25% CHO
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.426
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 80%; -0.56 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 50% CHO, Part A: LIK066 + 0% CHO
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 80%; -1.46 to -0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: LIK066 + 25% CHO, Part A: LIK066 + 0% CHO
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 80%; -1.25 to -0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + NS, Part B: LIK066 + 50% CHO + PS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.135
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 80%; -0.68 to -0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + NS, Part B: LIK066 + 50% CHO CC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.436
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 80%; -0.50 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part B: LIK066 + 50% CHO + PS, Part B: LIK066 + 50% CHO CC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.452
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 80%; -0.13 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Average Stool pH (Part A and Part B)
Description	Average PH of Stool at day 3
Time Frame	24 hours on Day 3 of each treatment period

Outcome Measure Data

Analysis Population Description

PD Analysis Set

Arm/Group Title	Part A: LIK066 + 50% CHO	Part A: LIK066 + 25% CHO	Part A: LIK066 + 0% CHO	Part B: LIK066 + 50% CHO + NS	Part B: LIK066 + 50% CHO + PS	Part B: LIK066 + 50% CHO CC
Arm/Group Description	Part A: LIK066 + 50% carbohydrate CHO	Part A: LIK066 + 25% carbohydrate CHO	Part A: LIK066 + 0% carbohydrate CHO	Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS)	Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS)	Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC)
Measure Participants	24	24	24	24	24	24
Mean (Standard Deviation) [pH]	6.35 (0.44)	6.50 (0.59)	6.29 (0.23)	6.52 (0.59)	6.79 (0.67)	6.66 (0.50)

5. Secondary Outcome

Title	Average Stool Weight (Part A and Part B)
Description	24 hour average stool weight on day 3
Time Frame	24 hours on Day 3 of each treatment period

Outcome Measure Data

Analysis Population Description

PD Analysis Set

Arm/Group Title	Part A: LIK066 + 50% CHO	Part A: LIK066 + 25% CHO	Part A: LIK066 + 0% CHO	Part B: LIK066 + 50% CHO + NS	Part B: LIK066 + 50% CHO + PS	Part B: LIK066 + 50% CHO CC
Arm/Group Description	Part A: LIK066 + 50% carbohydrate CHO	Part A: LIK066 + 25% carbohydrate CHO	Part A: LIK066 + 0% carbohydrate CHO	Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS)	Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS)	Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC)
Measure Participants	24	24	24	24	24	24
Mean (Standard Deviation) [gram]	136.5 (88.99)	154.5 (87.11)	116.7 (65.57)	145.5 (75.21)	177.1 (138.1)	164.3 (108.5)

Adverse Events

Time Frame	Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately22 days.
Arm/Group Title	Part A: LIK066 + 50% CHO		Part A: LIK066 + 25% CHO		Part A: LIK066 + 0% CHO		Part A: LIK066 + 8% CHO		Part B: LIK066 + 50% CHO + NS		Part B: LIK066 + 50% CHO + PS		Part B: LIK066 + 50% CHO CC
Arm/Group Description	Part A: LIK066 + 50% carbohydrate CHO		Part A: LIK066 + 25% carbohydrate CHO		Part A: LIK066 + 0% carbohydrate CHO		Part A: LIK066 + 8% carbohydrate CHO		Daily dose of 50 mg LIK066+50% carbohydrate + no supplement (NS)		Daily dose of 50 mg LIK066+50% carbohydrate + 6 g psyllium (PS)		Daily dose of 50 mg LIK066+50% carbohydrate +1g calcium carbonate (CC)
All Cause Mortality
	Part A: LIK066 + 50% CHO		Part A: LIK066 + 25% CHO		Part A: LIK066 + 0% CHO		Part A: LIK066 + 8% CHO		Part B: LIK066 + 50% CHO + NS		Part B: LIK066 + 50% CHO + PS		Part B: LIK066 + 50% CHO CC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Serious Adverse Events
	Part A: LIK066 + 50% CHO		Part A: LIK066 + 25% CHO		Part A: LIK066 + 0% CHO		Part A: LIK066 + 8% CHO		Part B: LIK066 + 50% CHO + NS		Part B: LIK066 + 50% CHO + PS		Part B: LIK066 + 50% CHO CC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Part A: LIK066 + 50% CHO		Part A: LIK066 + 25% CHO		Part A: LIK066 + 0% CHO		Part A: LIK066 + 8% CHO		Part B: LIK066 + 50% CHO + NS		Part B: LIK066 + 50% CHO + PS		Part B: LIK066 + 50% CHO CC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/24 (87.5%)		19/24 (79.2%)		19/24 (79.2%)		5/6 (83.3%)		21/24 (87.5%)		19/24 (79.2%)		22/24 (91.7%)
Gastrointestinal disorders
Diarrhea	20/24 (83.3%)		17/24 (70.8%)		14/24 (58.3%)		3/6 (50%)		20/24 (83.3%)		17/24 (70.8%)		22/24 (91.7%)
Abdominal discomfort	1/24 (4.2%)		1/24 (4.2%)		1/24 (4.2%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Abdominal distension	1/24 (4.2%)		1/24 (4.2%)		3/24 (12.5%)		1/6 (16.7%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Abdominal pain	1/24 (4.2%)		0/24 (0%)		1/24 (4.2%)		0/6 (0%)		2/24 (8.3%)		1/24 (4.2%)		2/24 (8.3%)
Abdominal pain lower	1/24 (4.2%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Constipation	6/24 (25%)		1/24 (4.2%)		5/24 (20.8%)		1/6 (16.7%)		0/24 (0%)		2/24 (8.3%)		1/24 (4.2%)
Flatulence	1/24 (4.2%)		0/24 (0%)		0/24 (0%)		2/6 (33.3%)		2/24 (8.3%)		2/24 (8.3%)		4/24 (16.7%)
Gastrointestinal pain	0/24 (0%)		0/24 (0%)		1/24 (4.2%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Nausea	1/24 (4.2%)		0/24 (0%)		1/24 (4.2%)		0/6 (0%)		0/24 (0%)		1/24 (4.2%)		3/24 (12.5%)
Vomiting	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		1/24 (4.2%)		1/24 (4.2%)
Anorectal discomfort	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Dyspepsia	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		2/24 (8.3%)		1/24 (4.2%)
General disorders
Peripheral swelling	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Vessel puncture site pain	0/24 (0%)		0/24 (0%)		1/24 (4.2%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Injury, poisoning and procedural complications
Scratch	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/24 (4.2%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Back pain	1/24 (4.2%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Nervous system disorders
Dizziness	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Headache	0/24 (0%)		1/24 (4.2%)		1/24 (4.2%)		0/6 (0%)		2/24 (8.3%)		1/24 (4.2%)		3/24 (12.5%)
Burning sensation	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Renal and urinary disorders
Dysuria	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Skin and subcutaneous tissue disorders
Erythema	0/24 (0%)		1/24 (4.2%)		1/24 (4.2%)		0/6 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Pruritus	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Scab	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/6 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.