Effect of LIK066 on Reduction of Fatty Content in Livers of Obese Patients
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03205150
Collaborator
(none)
107
15
3
25.3
7.1
0.3
Study Details
Study Description
Brief Summary
The purpose of this study was to assess the effects of LIK066 on a variety of metabolic and inflammation biomarkers in patients with non-alcoholic steatohepatitis (NASH)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This was a a non-confirmatory, multicenter, patient and investigator blinded, randomized, placebo-controlled, parallel group study in patients with non-alcoholic steatohepatitis (NASH).
The study consisted of a 28 day screening period (Day -44 to Day -16), a baseline period of 14 days (Day -15 to Day -1), a treatment period of 12 weeks (Day 1 to Day 84), and a study completion evaluation approximately 28 days after the last drug administration. The patients were advised to maintain their recommended diet during the study.
Patients who met the inclusion/exclusion criteria at screening went to the study site for baseline assessments. All baseline safety evaluation results were available prior to the first dosing.
The study started by enrolling patients into the 150 mg and placebo arms with a randomization ratio of 2:1. After the enrollment of the first 33 patients, the 30 mg arm was added to the study and the randomization ratio changed to a 2:4:1 ratio (150 mg: 30 mg: placebo) to maintain the 2:2:1 ratio across the three groups (150 mg: 30 mg: placebo) at study completion.
Study Design
Study Type:
Interventional
Actual Enrollment
:
107 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A 12-week Randomized, Patient and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate the Efficacy of LIK066 in Obese Patients With Non-alcoholic Steatohepatitis (NASH)
Actual Study Start Date
:
Oct 4, 2017
Actual Primary Completion Date
:
Nov 11, 2019
Actual Study Completion Date
:
Nov 14, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LIK066 30 mg Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
Drug: LIK066
Film coated tablet of LIK066 either 30mg or 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84
|
| Experimental: LIK066 150 mg Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84 |
Drug: LIK066
Film coated tablet of LIK066 either 30mg or 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84
|
| Experimental: Placebo LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
Drug: Placebo
LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 [Baseline, Week 12]
Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits.
Secondary Outcome Measures
- Change From Baseline in Percent Liver Fat at Week 12 [Baseline, Week 12]
Percent (%) Liver fat was measured by Magnetic Resonance Imaging Proton Density Liver Fat Fraction(MRIPDFF). Patients underwent magnetic resonance imaging twice during the course of the study ( baseline and end of treatment) to quantitate liver fat.
- Percent Change From Baseline in Total Body Weight at Week 12 [Baseline, Week 12]
Body weight (to the nearest 0.1 kilogram [kg] was measured on a calibrated scale. The measurement was performed with the study subject in underwear and without shoes; or while wearing minimal indoor clothing.
- Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12 [Baseline, Week 12]
The markers of fibrosis assessed in this test comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during fibrogenesis as a result of activation of the hepatic stellate cell. The ELF test is a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis.
- Change From Baseline in the Concentration of Hyaluronic Acid at Week 12. [Baseline, Week 12]
Hyaluronic Acid is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).
- Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12. [Baseline, Week 12]
PIIINP is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).
- Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12. [Baseline, Week 12]
TIMP-1 is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).
- Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration [Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)]
Cmax is the observed maximum plasma concentration following drug administration (ng/mL)
- Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration [Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)]
Tmax is the time to reach the maximum concentration after drug administration (hour). The time points presented are the actual and not the planned time points.
- Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration [Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)]
AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (hour*ng/mL)
- Change From Baseline in Aspartate Aminotransferase (AST) at Week 12 [Baseline, Week 12]
Aspartate aminotransferase (AST) is an enzyme found in many cells of the body specifically those of the liver, heart and skeletal muscle. In healthy individuals, levels of AST in the blood are low. When liver or muscle cells are injured, they release AST into the blood. In this study, the blood levels of AST was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
EITHER
-Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3 in the absence of a histological diagnosis of alternative chronic liver disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening.
OR
Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening:
-
ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND
-
BMI greater than or equal to 27 kg/m2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m2 (in patients with a self identified Asian race) AND
-
Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10%
-
Patients must weigh no more than 150 kg (330 lbs) to participate in the study.
-
Male and female patients 18 years or older at the time of screening visit.
Exclusion Criteria:
-
History or presence of other concomitant liver diseases
-
History or current diagnosis of ECG abnormalities
-
Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study
-
Patients with contraindications to MRI imaging
-
Current or history of significant alcohol consumption
-
Clinical evidence of hepatic decompensation or severe liver impairment
-
Women of child bearing potential (unless on basic contraception methods)
-
Presence of liver cirrhosis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Baton Rouge | Louisiana | United States | 70808 |
| 2 | Novartis Investigative Site | Saint Louis | Missouri | United States | 63110 |
| 3 | Novartis Investigative Site | Knoxville | Tennessee | United States | 37920 |
| 4 | Novartis Investigative Site | Live Oak | Texas | United States | 78233 |
| 5 | Novartis Investigative Site | Caba | Buenos Aires | Argentina | C1056ABJ |
| 6 | Novartis Investigative Site | Buenos Aires | Argentina | C1120AAC | |
| 7 | Novartis Investigative Site | Montreal | Quebec | Canada | H3P 3P1 |
| 8 | Novartis Investigative Site | Haifa | Israel | 343621 | |
| 9 | Novartis Investigative Site | Ramat Gan | Israel | ||
| 10 | Novartis Investigative Site | Tel Aviv | Israel | 64239 | |
| 11 | Novartis Investigative Site | Leiden | Netherlands | 2333 CL | |
| 12 | Novartis Investigative Site | St-Petersburg | Russian Federation | 194358 | |
| 13 | Novartis Investigative Site | Chia-Yi | Taiwan | 60002 | |
| 14 | Novartis Investigative Site | Tainan | Taiwan | 70403 | |
| 15 | Novartis Investigative Site | Bangkok | Thailand | 10700 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03205150
Other Study ID Numbers:
- CLIK066X2204
- 2017-002046-71
First Posted:
Jul 2, 2017
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 107 participants were enrolled in 15 centers across 8 countries: Argentina (2), Canada (1), Israel (3), Netherlands (1), Russia federation (1), Taiwan (2), Thailand (1), United States (4). |
|---|---|
| Pre-assignment Detail | Participants were randomized in 2:2:1 ratio to the 3 groups: LIK066 150 mg, LIK066 30 mg and placebo. |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Period Title: Overall Study | |||
| STARTED | 43 | 43 | 21 |
| Safety Analysis Set | 43 | 43 | 21 |
| Pharmacokinetics (PK) Analysis Set | 42 | 36 | 0 |
| Pharmacodynamics (PD) Analysis Set | 43 | 41 | 21 |
| COMPLETED | 41 | 36 | 19 |
| NOT COMPLETED | 2 | 7 | 2 |
Baseline Characteristics
| Arm/Group Title | Placebo | LIK066 30 mg | LIK066 150 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Total of all reporting groups |
| Overall Participants | 21 | 43 | 43 | 107 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
48.0
(11.16)
|
53.1
(12.57)
|
49.5
(11.10)
|
50.7
(11.80)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
12
57.1%
|
25
58.1%
|
22
51.2%
|
59
55.1%
|
| Male |
9
42.9%
|
18
41.9%
|
21
48.8%
|
48
44.9%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White |
17
81%
|
34
79.1%
|
35
81.4%
|
86
80.4%
|
| Asian |
3
14.3%
|
8
18.6%
|
4
9.3%
|
15
14%
|
| Black or African American |
1
4.8%
|
1
2.3%
|
3
7%
|
5
4.7%
|
| Other |
0
0%
|
0
0%
|
1
2.3%
|
1
0.9%
|
Outcome Measures
| Title | Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 |
|---|---|
| Description | Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 40 | 34 | 20 |
| Mean (Standard Error) [Units per Liter (U/L)] |
-22.06
(4.16)
|
-30.41
(4.52)
|
-8.77
(5.99)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.075 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -13.29 | |
| Confidence Interval |
(2-Sided) 80% -22.80 to -3.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.35 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LIK066 150 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -21.64 | |
| Confidence Interval |
(2-Sided) 80% -31.33 to -11.94 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.49 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, LIK066 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.178 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 8.35 | |
| Confidence Interval |
(2-Sided) 80% 0.41 to 16.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.14 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Percent Liver Fat at Week 12 |
|---|---|
| Description | Percent (%) Liver fat was measured by Magnetic Resonance Imaging Proton Density Liver Fat Fraction(MRIPDFF). Patients underwent magnetic resonance imaging twice during the course of the study ( baseline and end of treatment) to quantitate liver fat. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 39 | 33 | 19 |
| Mean (Standard Error) [Percentage of Liver Fat] |
-4.40
(0.81)
|
-6.92
(0.87)
|
-2.67
(1.17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.235 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.73 | |
| Confidence Interval |
(2-Sided) 80% -3.60 to 0.14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.45 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LIK066 150 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -4.26 | |
| Confidence Interval |
(2-Sided) 80% -6.14 to -2.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.46 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, LIK066 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.52 | |
| Confidence Interval |
(2-Sided) 80% 0.98 to 4.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.19 |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline in Total Body Weight at Week 12 |
|---|---|
| Description | Body weight (to the nearest 0.1 kilogram [kg] was measured on a calibrated scale. The measurement was performed with the study subject in underwear and without shoes; or while wearing minimal indoor clothing. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 40 | 34 | 19 |
| Mean (Standard Error) [percentage change] |
-3.48
(0.47)
|
-4.51
(0.52)
|
-0.33
(0.68)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -3.15 | |
| Confidence Interval |
(2-Sided) 80% -4.22 to -2.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LIK066 150 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -4.18 | |
| Confidence Interval |
(2-Sided) 80% -5.28 to -3.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.85 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, LIK066 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.148 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 80% 0.12 to 1.94 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.71 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12 |
|---|---|
| Description | The markers of fibrosis assessed in this test comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during fibrogenesis as a result of activation of the hepatic stellate cell. The ELF test is a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 40 | 34 | 21 |
| Mean (Standard Deviation) [scores on a scale] |
-0.2
(0.65)
|
-0.1
(0.61)
|
0.1
(0.37)
|
| Title | Change From Baseline in the Concentration of Hyaluronic Acid at Week 12. |
|---|---|
| Description | Hyaluronic Acid is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 40 | 34 | 21 |
| Mean (Standard Deviation) [ug/L] |
-3.4
(75.38)
|
0.4
(30.56)
|
4.7
(21.73)
|
| Title | Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12. |
|---|---|
| Description | PIIINP is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 40 | 34 | 20 |
| Mean (Standard Deviation) [ug/L] |
-1.7
(2.73)
|
-1.2
(3.66)
|
0.3
(1.88)
|
| Title | Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12. |
|---|---|
| Description | TIMP-1 is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 40 | 34 | 20 |
| Mean (Standard Deviation) [ug/L] |
-3.0
(38.98)
|
-10.9
(38.21)
|
10.3
(25.73)
|
| Title | Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration |
|---|---|
| Description | Cmax is the observed maximum plasma concentration following drug administration (ng/mL) |
| Time Frame | Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set consisted of LIK066 treated patients. Placebo patients were excluded from the PK analysis |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg |
|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 38 | 32 |
| Mean (Standard Deviation) [ng/mL] |
405
(109)
|
1810
(729)
|
| Title | Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration |
|---|---|
| Description | Tmax is the time to reach the maximum concentration after drug administration (hour). The time points presented are the actual and not the planned time points. |
| Time Frame | Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set consisted of LIK066 treated patients. Placebo patients were excluded from the PK analysis |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg |
|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 38 | 32 |
| Median (Full Range) [hours] |
1.00
|
1.51
|
| Title | Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration |
|---|---|
| Description | AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (hour*ng/mL) |
| Time Frame | Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set consisted of LIK066 treated patients. Placebo patients were excluded from the PK analysis |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg |
|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 38 | 32 |
| Mean (Standard Deviation) [hour*ng/mL] |
1280
(413)
|
5770
(1680)
|
| Title | Change From Baseline in Aspartate Aminotransferase (AST) at Week 12 |
|---|---|
| Description | Aspartate aminotransferase (AST) is an enzyme found in many cells of the body specifically those of the liver, heart and skeletal muscle. In healthy individuals, levels of AST in the blood are low. When liver or muscle cells are injured, they release AST into the blood. In this study, the blood levels of AST was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure |
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. |
| Measure Participants | 40 | 34 | 20 |
| Mean (Standard Error) [Units per liter (U/L)] |
-13.45
(2.46)
|
-17.01
(2.68)
|
-2.30
(3.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.013 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -11.15 | |
| Confidence Interval |
(2-Sided) 80% -16.79 to -5.50 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.36 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LIK066 150 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -14.71 | |
| Confidence Interval |
(2-Sided) 80% -20.43 to -8.98 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.43 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LIK066 30 mg, LIK066 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.332 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 3.56 | |
| Confidence Interval |
(2-Sided) 80% -1.15 to 8.28 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.65 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Adverse events were collected from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Any signs or symptoms that occured from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period. | |||||||
| Arm/Group Title | LIK066 30 mg | LIK066 150 mg | Placebo | All Patients | ||||
| Arm/Group Description | Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84. | All Patients | ||||
All Cause Mortality |
||||||||
| LIK066 30 mg | LIK066 150 mg | Placebo | All Patients | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/43 (0%) | 0/43 (0%) | 0/21 (0%) | 0/107 (0%) | ||||
Serious Adverse Events |
||||||||
| LIK066 30 mg | LIK066 150 mg | Placebo | All Patients | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Infections and infestations | ||||||||
| Gastroenteritis viral | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| LIK066 30 mg | LIK066 150 mg | Placebo | All Patients | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 31/43 (72.1%) | 36/43 (83.7%) | 18/21 (85.7%) | 85/107 (79.4%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Neutropenia | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Cardiac disorders | ||||||||
| Palpitations | 0/43 (0%) | 1/43 (2.3%) | 1/21 (4.8%) | 2/107 (1.9%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vertigo | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Eye disorders | ||||||||
| Glaucoma | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Abdominal distension | 2/43 (4.7%) | 6/43 (14%) | 0/21 (0%) | 8/107 (7.5%) | ||||
| Abdominal pain | 1/43 (2.3%) | 5/43 (11.6%) | 2/21 (9.5%) | 8/107 (7.5%) | ||||
| Abdominal pain upper | 0/43 (0%) | 3/43 (7%) | 2/21 (9.5%) | 5/107 (4.7%) | ||||
| Abdominal tenderness | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Anal pruritus | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Colitis | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Constipation | 2/43 (4.7%) | 3/43 (7%) | 1/21 (4.8%) | 6/107 (5.6%) | ||||
| Diarrhoea | 21/43 (48.8%) | 33/43 (76.7%) | 9/21 (42.9%) | 63/107 (58.9%) | ||||
| Dyspepsia | 1/43 (2.3%) | 1/43 (2.3%) | 1/21 (4.8%) | 3/107 (2.8%) | ||||
| Flatulence | 2/43 (4.7%) | 8/43 (18.6%) | 2/21 (9.5%) | 12/107 (11.2%) | ||||
| Gastric dilatation | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Gastric ulcer | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Gastrooesophageal reflux disease | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Haemorrhoids | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Large intestine polyp | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Nausea | 4/43 (9.3%) | 3/43 (7%) | 3/21 (14.3%) | 10/107 (9.3%) | ||||
| Toothache | 1/43 (2.3%) | 1/43 (2.3%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Vomiting | 5/43 (11.6%) | 2/43 (4.7%) | 2/21 (9.5%) | 9/107 (8.4%) | ||||
| General disorders | ||||||||
| Asthenia | 1/43 (2.3%) | 1/43 (2.3%) | 1/21 (4.8%) | 3/107 (2.8%) | ||||
| Chills | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Early satiety | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Fatigue | 2/43 (4.7%) | 3/43 (7%) | 0/21 (0%) | 5/107 (4.7%) | ||||
| Feeling hot | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Feeling jittery | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Hunger | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Pyrexia | 0/43 (0%) | 1/43 (2.3%) | 1/21 (4.8%) | 2/107 (1.9%) | ||||
| Thirst | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Vessel puncture site bruise | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Hepatic cirrhosis | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Portal hypertension | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Immune system disorders | ||||||||
| Allergy to arthropod bite | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Fungal infection | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Furuncle | 1/43 (2.3%) | 0/43 (0%) | 1/21 (4.8%) | 2/107 (1.9%) | ||||
| Gastroenteritis | 1/43 (2.3%) | 1/43 (2.3%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Gastroenteritis viral | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Gingival abscess | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Influenza | 4/43 (9.3%) | 0/43 (0%) | 0/21 (0%) | 4/107 (3.7%) | ||||
| Nasopharyngitis | 0/43 (0%) | 3/43 (7%) | 1/21 (4.8%) | 4/107 (3.7%) | ||||
| Oral herpes | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Otitis externa | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Rhinitis | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Sinusitis | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Upper respiratory tract infection | 3/43 (7%) | 0/43 (0%) | 1/21 (4.8%) | 4/107 (3.7%) | ||||
| Urinary tract infection | 2/43 (4.7%) | 0/43 (0%) | 1/21 (4.8%) | 3/107 (2.8%) | ||||
| Vaginal infection | 0/43 (0%) | 2/43 (4.7%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Viral infection | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Vulvovaginal mycotic infection | 0/43 (0%) | 2/43 (4.7%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Joint injury | 2/43 (4.7%) | 0/43 (0%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 2/43 (4.7%) | 0/43 (0%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Aspartate aminotransferase increased | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Blood bilirubin increased | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Blood cholesterol increased | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Blood triglycerides increased | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Electrocardiogram QT prolonged | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Heart rate irregular | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Lymphocyte morphology abnormal | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/43 (2.3%) | 0/43 (0%) | 1/21 (4.8%) | 2/107 (1.9%) | ||||
| Diabetes mellitus | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Food craving | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Hypercholesterolaemia | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Hypoglycaemia | 2/43 (4.7%) | 0/43 (0%) | 1/21 (4.8%) | 3/107 (2.8%) | ||||
| Hypovitaminosis | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Polydipsia | 2/43 (4.7%) | 1/43 (2.3%) | 0/21 (0%) | 3/107 (2.8%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Arthritis | 1/43 (2.3%) | 1/43 (2.3%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Back pain | 0/43 (0%) | 1/43 (2.3%) | 1/21 (4.8%) | 2/107 (1.9%) | ||||
| Muscle spasms | 0/43 (0%) | 1/43 (2.3%) | 2/21 (9.5%) | 3/107 (2.8%) | ||||
| Muscular weakness | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Musculoskeletal chest pain | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Myalgia | 0/43 (0%) | 0/43 (0%) | 2/21 (9.5%) | 2/107 (1.9%) | ||||
| Neck pain | 1/43 (2.3%) | 2/43 (4.7%) | 1/21 (4.8%) | 4/107 (3.7%) | ||||
| Osteitis | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 0/43 (0%) | 4/43 (9.3%) | 3/21 (14.3%) | 7/107 (6.5%) | ||||
| Head discomfort | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Headache | 2/43 (4.7%) | 5/43 (11.6%) | 3/21 (14.3%) | 10/107 (9.3%) | ||||
| Hypoaesthesia | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Somnolence | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Tremor | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 2/43 (4.7%) | 0/43 (0%) | 0/21 (0%) | 2/107 (1.9%) | ||||
| Depression | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Insomnia | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Mood swings | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Nervousness | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Renal and urinary disorders | ||||||||
| Ketonuria | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Microalbuminuria | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Nocturia | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Polyuria | 4/43 (9.3%) | 1/43 (2.3%) | 1/21 (4.8%) | 6/107 (5.6%) | ||||
| Proteinuria | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Urinary incontinence | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Reproductive system and breast disorders | ||||||||
| Nipple pain | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Epistaxis | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Nasal congestion | 1/43 (2.3%) | 0/43 (0%) | 1/21 (4.8%) | 2/107 (1.9%) | ||||
| Productive cough | 0/43 (0%) | 1/43 (2.3%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Rhinorrhoea | 0/43 (0%) | 1/43 (2.3%) | 1/21 (4.8%) | 2/107 (1.9%) | ||||
| Wheezing | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Night sweats | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
| Papule | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Vascular disorders | ||||||||
| Diastolic hypotension | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Hypertension | 1/43 (2.3%) | 0/43 (0%) | 0/21 (0%) | 1/107 (0.9%) | ||||
| Peripheral coldness | 0/43 (0%) | 0/43 (0%) | 1/21 (4.8%) | 1/107 (0.9%) | ||||
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| Novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03205150
Other Study ID Numbers:
- CLIK066X2204
- 2017-002046-71
First Posted:
Jul 2, 2017
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021