Effect of LIK066 on Body Weight in Patients With Elevated Body Mass Index
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02470403
Collaborator
(none)
181
1
5
10
18.1
Study Details
Study Description
Brief Summary
A 12-week study to assess LIK066 effect on body weight in diabetics, prediabetics and normoglycemic patients with elevated body mass index (BMI)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
181 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
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
Actual Study Start Date
:
Jun 5, 2015
Actual Primary Completion Date
:
Apr 4, 2016
Actual Study Completion Date
:
Apr 4, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: LIK066 150 mg once daily (qd) LIK066 150 mg qd within 15 minutes before starting lunch |
Drug: LIK066
LIK066 25 mg tablets
|
| Placebo Comparator: Part 1: Placebo once daily Matching placebo tablets of LCZ696 150 mg within 15 minutes before starting lunch. |
Drug: LIK066
LIK066 25 mg tablets
|
| Experimental: Part 2: LIK066 75 mg twice daily (bid) LIK066 75 mg bid before breakfast and dinner |
Drug: Placebo
Matching placebo tablets
|
| Experimental: Part 2: LIK066 50 mg three times daily (tid) LIK066 50 mg tid before all 3 meals; |
Drug: Placebo
Matching placebo tablets
|
| Placebo Comparator: Part 2: Placebo three times daily Matching placebo tablets tid before meals. |
Drug: LIK066
LIK066 25 mg tablets
|
Outcome Measures
Primary Outcome Measures
- Part 1: Percent Change in Body Weight From Baseline to Week 12 [Baseline, Week 12 (Day 85)]
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.
- Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death [12 weeks]
This endpoint reports patients with at least one AE (any AE), serious AE and death.
- Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) [Baseline, 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.
- Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death [2 weeks]
This endpoint reports patients with at least one AE (any AE), serious AE and death
Secondary Outcome Measures
- Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms [Baseline, Week 2]
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.
- Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study [Day 84]
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.
- Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study [Day 84]
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.
- 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 [Day 84]
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.
- 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 [Day 84]
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.
- The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study [Day 84]
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 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 [Day 84]
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.
- Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study [Day 1, Day 14]
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)
- Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study [Day 1, Day 14]
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)
- Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study [Day 1, Day 14]
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)
- Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study [Day 1, Day 14]
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)
- The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study [Day 1, Day 14]
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)
- The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study [Day 1, Day 14]
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)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
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: Study Director, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02470403
Other Study ID Numbers:
- CLIK066X2201
First Posted:
Jun 12, 2015
Last Update Posted:
Jan 5, 2021
Last Verified:
Mar 1, 2019
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Subjects were stratified by their glycemic status (dysglycemic or normoglycemic) and randomized to LIK066 or placebo within each stratum in each part of the study. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily |
|---|---|---|---|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch | Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch. | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; | Matching placebo tablets tid before meals. |
| Period Title: Overall Study | |||||
| STARTED | 44 | 44 | 40 | 43 | 10 |
| Dysglycemic | 24 | 24 | 20 | 20 | 5 |
| Normoglycemic | 20 | 20 | 20 | 23 | 5 |
| COMPLETED | 42 | 43 | 40 | 39 | 10 |
| NOT COMPLETED | 2 | 1 | 0 | 4 | 0 |
Baseline Characteristics
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch | Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch. | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; | Matching placebo tablets tid before meals. | Total of all reporting groups |
| Overall Participants | 44 | 44 | 40 | 43 | 10 | 181 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Part 1 (44, 44, NA,NA,NA,88) |
39.0
(12.01)
|
41.3
(11.07)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
40.2
(11.54)
|
| Part 2 (NA, NA, 40,43,10,93) |
NA
(NA)
|
NA
(NA)
|
42.9
(8.96)
|
39.9
(11.22)
|
43.4
(12.39)
|
41.6
(10.44)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
19
43.2%
|
26
59.1%
|
26
65%
|
26
60.5%
|
8
80%
|
105
58%
|
| Male |
25
56.8%
|
18
40.9%
|
14
35%
|
17
39.5%
|
2
20%
|
76
42%
|
Outcome Measures
| Title | Part 1: Percent Change in Body Weight From Baseline to Week 12 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 12 (Day 85) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamics (PD) analysis set included all subjects with available PD data and no protocol deviations with relevant impact on PD data. The analysis is based on all subjects with a Baseline body weight and at least one post-Baseline body weight measurement. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily |
|---|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch | Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch. |
| Measure Participants | 44 | 43 |
| All subjects (n= 42, 43) |
-5.51
|
0.19
|
| Dysglycemic subjects (n= 22, 23) |
-6.55
|
0.29
|
| Normoglycemic subjects (n= 20,20) |
-4.46
|
0.09
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1: LIK066 150 mg Once Daily (qd), Part 1: Placebo Once Daily |
|---|---|---|
| Comments | This analysis included all subjects. The following criteria were assessed: upper confidence limit of the 80% CI for treatment difference (LIK066 - placebo) was less than 0, and estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -5.70 | |
| Confidence Interval |
(2-Sided) 80% -6.52 to -4.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part 1: LIK066 150 mg Once Daily (qd), Part 1: Placebo Once Daily |
|---|---|---|
| Comments | This analysis included dysglycemic subjects. The following criteria were assessed: upper confidence limit of 80% CI for treatment difference was less than 0, and estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -6.85 | |
| Confidence Interval |
(2-Sided) 80% -7.96 to -5.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part 1: LIK066 150 mg Once Daily (qd), Part 1: Placebo Once Daily |
|---|---|---|
| Comments | This analysis included normoglycemic subjects. The following criteria were assessed: upper confidence limit of 80% CI for treatment difference was less than 0, and estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -4.55 | |
| Confidence Interval |
(2-Sided) 80% -5.76 to -3.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death |
|---|---|
| Description | This endpoint reports patients with at least one AE (any AE), serious AE and death. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all subjects that received any study drug. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily |
|---|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch | Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch. |
| Measure Participants | 44 | 44 |
| With at least one AE (any AE) |
43
|
39
|
| Serious AE |
1
|
0
|
| Death |
0
|
0
|
| Title | Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 2 (Day 14) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic set. The analysis was based on all subjects with a baseline body weight and at least one post-Baseline body weight measurement. Only data from common time points in Part 1 and Part 2 were included in the analysis, i.e., Baseline and Day 14. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 1 and 2 : Pooled Placebo |
|---|---|---|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; | Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses |
| Measure Participants | 44 | 40 | 39 | 53 |
| Least Squares Mean (80% Confidence Interval) [Percent change] |
-1.17
|
-1.73
|
-1.71
|
0.66
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1: LIK066 150 mg Once Daily (qd), Part 1 and 2 : Pooled Placebo |
|---|---|---|
| Comments | This analysis on all subjects. The following criteria were assessed: upper confidence limit of 80% CI for treatment difference was less than 0, and estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.83 | |
| Confidence Interval |
(2-Sided) 80% -2.16 to -1.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part 1: Placebo Once Daily, Part 1 and 2 : Pooled Placebo |
|---|---|---|
| Comments | This analysis on all subjects. The following criteria were assessed: upper confidence limit of 80% CI for treatment difference was less than 0, and estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -2.39 | |
| Confidence Interval |
(2-Sided) 80% -2.94 to -1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part 2: LIK066 50 mg Three Times Daily (Tid), Part 1 and 2 : Pooled Placebo |
|---|---|---|
| Comments | This analysis on all subjects. The following criteria were assessed: upper confidence limit of 80% CI for treatment difference was less than 0, and estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5% | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -2.38 | |
| Confidence Interval |
(2-Sided) 80% -2.93 to -1.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death |
|---|---|
| Description | This endpoint reports patients with at least one AE (any AE), serious AE and death |
| Time Frame | 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all subjects that received any study drug. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily |
|---|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; | Matching placebo tablets tid before meals. |
| Measure Participants | 40 | 43 | 10 |
| At least one AE (Any AE) |
40
|
43
|
10
|
| Serious AE |
0
|
0
|
0
|
| Death |
0
|
0
|
0
|
| Title | Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamics (PD) analysis set included all subjects with available PD data and no protocol deviations with relevant impact on PD data. The analysis is based on all subjects with a Baseline body weight and at least one post-Baseline body weight measurement. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) |
|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; |
| Measure Participants | 40 | 43 |
| Dysglycemic (n= 20, 19) |
-1.99
|
-1.73
|
| Normoglycemic (n=20, 20) |
-1.46
|
-1.70
|
| Title | Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study |
|---|---|
| Description | 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. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) |
|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch |
| Measure Participants | 40 |
| Dysglycemic (n=22) |
1230
(328)
|
| Normoglycemic (n=18) |
1220
(327)
|
| Overall (n=40) |
1230
(323)
|
| Title | Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study |
|---|---|
| Description | 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. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) |
|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch |
| Measure Participants | 40 |
| Dysglycemic (n=22) |
3.02
|
| Normoglycemic (n=18) |
4.02
|
| Overall (n=40) |
3.02
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) |
|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch |
| Measure Participants | 40 |
| Dysglycemic (n=22) |
11600
(3260)
|
| Normoglycemic (n=18) |
12800
(4860)
|
| Overall (n=40) |
12100
(4050)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) |
|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch |
| Measure Participants | 40 |
| Dysglycemic (n=22) |
11600
(3260)
|
| Normoglycemic (n=18) |
12800
(4860)
|
| Overall (n=40) |
12100
(4050)
|
| Title | The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study |
|---|---|
| Description | 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. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) |
|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch |
| Measure Participants | 40 |
| Dysglycemic (n=22) |
14.1
(4.67)
|
| Normoglycemic (n=18) |
13.2
(4.42)
|
| Overall (n=40) |
13.7
(4.52)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) |
|---|---|
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch |
| Measure Participants | 40 |
| Dysglycemic (n=14) |
110
(23.8)
|
| Normoglycemic (n=8) |
106
(31.2)
|
| Overall (n=22) |
109
(26.1)
|
| Title | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study |
|---|---|
| Description | 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) |
| Time Frame | Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) |
|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; |
| Measure Participants | 40 | 39 |
| Day 1, Dysglycemic (n= 19, 20) |
728
(274)
|
513
(176)
|
| Day 1, Normoglycemic (n= 19, 19) |
767
(275)
|
517
(223)
|
| Day 1, Overall (n= 38, 39) |
747
(272)
|
515
(198)
|
| Day 14, Dysglycemic (n= 20, 19) |
1100
(361)
|
716
(282)
|
| Day 14, Normoglycemic (n= 20, 19) |
1030
(266)
|
792
(276)
|
| Day 14, Overall (n= 40, 38) |
1070
(315)
|
754
(278)
|
| Title | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study |
|---|---|
| Description | 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) |
| Time Frame | Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) |
|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; |
| Measure Participants | 40 | 39 |
| Day 1, Dysglycemic (n= 19, 20) |
1.00
(274)
|
1.00
(176)
|
| Day 1, Normoglycemic (n= 19, 19) |
1.00
(275)
|
0.983
(223)
|
| Day 1, Overall (n= 38, 39) |
1.00
(272)
|
1.00
(198)
|
| Day 14, Dysglycemic (n= 20, 19) |
0.983
(361)
|
1.00
(282)
|
| Day 14, Normoglycemic (n= 20, 19) |
1.00
(266)
|
0.533
(276)
|
| Day 14, Overall (n= 40, 38) |
0.992
(315)
|
1.00
(278)
|
| Title | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study |
|---|---|
| Description | 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) |
| Time Frame | Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) |
|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; |
| Measure Participants | 40 | 39 |
| Day 1, Dysglycemic (n= 19, 20) |
3160
(571)
|
3910
(840)
|
| Day 1, Normoglycemic (n= 19, 19) |
3280
(674)
|
3870
(1360)
|
| Day 1, Overall (n= 38, 39) |
3220
(619)
|
3890
(1110)
|
| Day 14, Dysglycemic (n= 20, 19) |
4600
(1050)
|
4740
(1200)
|
| Day 14, Normoglycemic (n= 20, 19) |
4300
(1160)
|
4950
(1580)
|
| Day 14, Overall (n= 40, 38) |
4450
(1100)
|
4850
(1390)
|
| Title | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study |
|---|---|
| Description | 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) |
| Time Frame | Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) |
|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; |
| Measure Participants | 40 | 39 |
| Day 1, Dysglycemic (n= 19, 20) |
3170
(573)
|
1340
(295)
|
| Day 1, Normoglycemic (n= 18, 19) |
3290
(699)
|
1350
(429)
|
| Day 1, Overall (n= 37, 39) |
3230
(632)
|
1350
(362)
|
| Day 14, Dysglycemic (n= 20, 19) |
4620
(1060)
|
1940
(600)
|
| Day 14, Normoglycemic (n= 20, 19) |
4310
(1160)
|
2000
(586)
|
| Day 14, Overall (n= 40, 38) |
4470
(1100)
|
1970
(586)
|
| Title | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study |
|---|---|
| Description | 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) |
| Time Frame | Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) |
|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; |
| Measure Participants | 40 | 39 |
| Day 1, Dysglycemic (n= 19, 20) |
24.3
(3.97)
|
39.3
(9.42)
|
| Day 1, Normoglycemic (n= 18, 19) |
23.8
(5.28)
|
40.5
(12.8)
|
| Day 1, Overall (n= 37, 39) |
24.1
(4.59)
|
39.9
(11.1)
|
| Day 14, Dysglycemic (n= 20, 19) |
17.1
(4.05)
|
27.8
(7.35)
|
| Day 14, Normoglycemic (n= 20, 19) |
18.5
(4.72)
|
27.2
(8.50)
|
| Day 14, Overall (n= 40, 38) |
17.8
(4.40)
|
27.5
(7.84)
|
| Title | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study |
|---|---|
| Description | 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) |
| Time Frame | Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data. |
| Arm/Group Title | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) |
|---|---|---|
| Arm/Group Description | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; |
| Measure Participants | 40 | 39 |
| Day 1, Dysglycemic (n= 19, 19) |
132
(51.7)
|
274
(224)
|
| Day 1, Normoglycemic (n= 18, 17) |
127
(42.4)
|
519
(1330)
|
| Day 1, Overall (n= 37, 36) |
130
(46.8)
|
390
(919)
|
| Day 14, Dysglycemic (n= 20, 16) |
108
(52.5)
|
580
(1380)
|
| Day 14, Normoglycemic (n= 20, 19) |
112
(34.1)
|
267
(493)
|
| Day 14, Overall (n= 40, 35) |
110
(43.7)
|
410
(997)
|
Adverse Events
| Time Frame | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily | |||||
| Arm/Group Description | LIK066 150 mg qd within 15 minutes before starting lunch | Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch. | LIK066 75 mg bid before breakfast and dinner | LIK066 50 mg tid before all 3 meals; | Matching placebo tablets tid before meals. | |||||
All Cause Mortality |
||||||||||
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Infections and infestations | ||||||||||
| Appendicitis perforated | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 43/44 (97.7%) | 39/44 (88.6%) | 40/40 (100%) | 43/43 (100%) | 10/10 (100%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 0/44 (0%) | 1/44 (2.3%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Eye disorders | ||||||||||
| Visual impairment | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 2/44 (4.5%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Abdominal distension | 11/44 (25%) | 4/44 (9.1%) | 9/40 (22.5%) | 9/43 (20.9%) | 0/10 (0%) | |||||
| Abdominal pain | 12/44 (27.3%) | 5/44 (11.4%) | 5/40 (12.5%) | 8/43 (18.6%) | 0/10 (0%) | |||||
| Abdominal pain lower | 3/44 (6.8%) | 0/44 (0%) | 1/40 (2.5%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Abdominal pain upper | 1/44 (2.3%) | 1/44 (2.3%) | 2/40 (5%) | 2/43 (4.7%) | 0/10 (0%) | |||||
| Abdominal tenderness | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 2/43 (4.7%) | 0/10 (0%) | |||||
| Abnormal faeces | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 1/10 (10%) | |||||
| Anal haemorrhage | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Anorectal discomfort | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Constipation | 1/44 (2.3%) | 2/44 (4.5%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Diarrhoea | 40/44 (90.9%) | 11/44 (25%) | 40/40 (100%) | 42/43 (97.7%) | 8/10 (80%) | |||||
| Dry mouth | 1/44 (2.3%) | 1/44 (2.3%) | 2/40 (5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Dyspepsia | 6/44 (13.6%) | 4/44 (9.1%) | 4/40 (10%) | 4/43 (9.3%) | 0/10 (0%) | |||||
| Eructation | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Faeces hard | 0/44 (0%) | 0/44 (0%) | 10/40 (25%) | 8/43 (18.6%) | 6/10 (60%) | |||||
| Flatulence | 19/44 (43.2%) | 4/44 (9.1%) | 9/40 (22.5%) | 12/43 (27.9%) | 0/10 (0%) | |||||
| Gastrointestinal sounds abnormal | 0/44 (0%) | 0/44 (0%) | 4/40 (10%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Haematochezia | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Nausea | 8/44 (18.2%) | 3/44 (6.8%) | 5/40 (12.5%) | 8/43 (18.6%) | 0/10 (0%) | |||||
| Palatal disorder | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Proctalgia | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Toothache | 0/44 (0%) | 2/44 (4.5%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Vomiting | 3/44 (6.8%) | 3/44 (6.8%) | 6/40 (15%) | 4/43 (9.3%) | 1/10 (10%) | |||||
| General disorders | ||||||||||
| Asthenia | 1/44 (2.3%) | 0/44 (0%) | 1/40 (2.5%) | 2/43 (4.7%) | 0/10 (0%) | |||||
| Chills | 0/44 (0%) | 0/44 (0%) | 2/40 (5%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Energy increased | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Fatigue | 0/44 (0%) | 0/44 (0%) | 2/40 (5%) | 4/43 (9.3%) | 0/10 (0%) | |||||
| Feeling hot | 2/44 (4.5%) | 1/44 (2.3%) | 1/40 (2.5%) | 2/43 (4.7%) | 0/10 (0%) | |||||
| Feeling jittery | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Local swelling | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Medical device site dermatitis | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Oedema peripheral | 0/44 (0%) | 2/44 (4.5%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Pain | 0/44 (0%) | 1/44 (2.3%) | 1/40 (2.5%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Pyrexia | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 1/10 (10%) | |||||
| Thirst | 1/44 (2.3%) | 0/44 (0%) | 1/40 (2.5%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Infections and infestations | ||||||||||
| Bacterial vaginosis | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Parotitis | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Sinusitis | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Trichomoniasis | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Urinary tract infection | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Vulvovaginal candidiasis | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Vulvovaginal mycotic infection | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Animal scratch | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Fall | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Laceration | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 1/10 (10%) | |||||
| Mouth injury | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Skin abrasion | 2/44 (4.5%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Wrist fracture | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Investigations | ||||||||||
| Blood pressure increased | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Blood triglycerides increased | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Blood urine present | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Fungal test positive | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Heart rate increased | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 3/44 (6.8%) | 1/44 (2.3%) | 3/40 (7.5%) | 6/43 (14%) | 0/10 (0%) | |||||
| Hypoglycaemia | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Increased appetite | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/44 (0%) | 2/44 (4.5%) | 0/40 (0%) | 0/43 (0%) | 1/10 (10%) | |||||
| Back pain | 2/44 (4.5%) | 2/44 (4.5%) | 0/40 (0%) | 3/43 (7%) | 0/10 (0%) | |||||
| Flank pain | 0/44 (0%) | 1/44 (2.3%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Muscle spasms | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Musculoskeletal pain | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Myalgia | 2/44 (4.5%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Neck pain | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Pain in extremity | 0/44 (0%) | 1/44 (2.3%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Nervous system disorders | ||||||||||
| Burning sensation | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Dizziness | 1/44 (2.3%) | 1/44 (2.3%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Dizziness postural | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Dysgeusia | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Headache | 9/44 (20.5%) | 16/44 (36.4%) | 13/40 (32.5%) | 10/43 (23.3%) | 2/10 (20%) | |||||
| Hypoaesthesia | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Hypogeusia | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Migraine | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Presyncope | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Sinus headache | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Somnolence | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Insomnia | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 2/10 (20%) | |||||
| Renal and urinary disorders | ||||||||||
| Dysuria | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Nephrolithiasis | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Pollakiuria | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Metrorrhagia | 0/44 (0%) | 0/44 (0%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Vaginal discharge | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Vulvovaginal pruritus | 1/44 (2.3%) | 0/44 (0%) | 1/40 (2.5%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 2/44 (4.5%) | 5/44 (11.4%) | 4/40 (10%) | 1/43 (2.3%) | 2/10 (20%) | |||||
| Epistaxis | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Nasal congestion | 0/44 (0%) | 3/44 (6.8%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Oropharyngeal pain | 3/44 (6.8%) | 6/44 (13.6%) | 2/40 (5%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Paranasal sinus discomfort | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Productive cough | 1/44 (2.3%) | 2/44 (4.5%) | 0/40 (0%) | 2/43 (4.7%) | 0/10 (0%) | |||||
| Respiratory tract congestion | 2/44 (4.5%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Rhinorrhoea | 1/44 (2.3%) | 2/44 (4.5%) | 3/40 (7.5%) | 2/43 (4.7%) | 0/10 (0%) | |||||
| Sinus congestion | 3/44 (6.8%) | 2/44 (4.5%) | 1/40 (2.5%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Throat irritation | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Wheezing | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Cold sweat | 1/44 (2.3%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 1/10 (10%) | |||||
| Ecchymosis | 0/44 (0%) | 1/44 (2.3%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Erythema | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 0/10 (0%) | |||||
| Hyperhidrosis | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Pruritus | 2/44 (4.5%) | 0/44 (0%) | 1/40 (2.5%) | 1/43 (2.3%) | 1/10 (10%) | |||||
| Rash | 0/44 (0%) | 1/44 (2.3%) | 1/40 (2.5%) | 0/43 (0%) | 0/10 (0%) | |||||
| Rash erythematous | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 2/43 (4.7%) | 0/10 (0%) | |||||
| Rash maculo-papular | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 0/43 (0%) | 1/10 (10%) | |||||
| Vascular disorders | ||||||||||
| Hot flush | 1/44 (2.3%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
| Hypertension | 0/44 (0%) | 0/44 (0%) | 0/40 (0%) | 1/43 (2.3%) | 0/10 (0%) | |||||
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| trialandresults.registries@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02470403
Other Study ID Numbers:
- CLIK066X2201
First Posted:
Jun 12, 2015
Last Update Posted:
Jan 5, 2021
Last Verified:
Mar 1, 2019