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A Study to Evaluate the Change in Weight After 24 Weeks Treatment With LIK066 in Obese or Overweight Adults

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03100058
Collaborator
(none)
460
Enrollment
83
Locations
13
Arms
14.9
Actual Duration (Months)
5.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was a dose-finding study that evaluated the change in weight after 24 weeks treatment with 8 different doses of LIK066 compared to placebo in obese or overweight adults, followed by 24 weeks treatment with 2 doses of LIK066 and placebo.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
460 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Dose-finding Study to Evaluate the Change in Weight After 24 Weeks Treatment With 8 Doses of LIK066 Compared to Placebo in Obese or Overweight Adults, Followed by 24 Weeks Treatment With 2 Doses of LIK066 and Placebo
Actual Study Start Date :
May 6, 2017
Actual Primary Completion Date :
Mar 2, 2018
Actual Study Completion Date :
Aug 2, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: LIK066 2.5mg qd (Epoch 3)

LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks.

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Placebo Comparator: Placebo (Epoch 3)

Matching placebo tablets for 24 weeks

Drug: Placebo
Placebo
Experimental: LIK066 10mg qd (Epoch 3)

LIK066 10mg qd (once daily) dosing frequency for 24 weeks

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 50mg qd (Epoch 3)

LIK066 50mg qd (once daily) dosing frequency for 24 weeks

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 150mg qd (Epoch 3)

LIK066 150mg qd (once daily) dosing frequency for 24 weeks

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 2.5mg bid (Epoch 3)

LIK066 2.5mg bid (once daily) dosing frequency for 24 weeks

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 5mg bid (Epoch 3)

LIK066 5mg bid (once daily) dosing frequency for 24 weeks

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 25mg bid (Epoch 3)

LIK066 25mg bid (once daily) dosing frequency for 24 weeks

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 50mg bid (Epoch 3)

LIK066 50mg bid dosing frequency for 24 weeks

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 qd/LIK066 25mg qd (Epoch 4)

Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: LIK066 bid/LIK066 35mg qd (Epoch 4)

Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Experimental: Placebo/LIK066 25mg qd (Epoch 4)

Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily

Drug: LIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
Placebo Comparator: Placebo/Placebo (Epoch 4)

Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily

Drug: Placebo
Placebo

Outcome Measures

Primary Outcome Measures

  1. Percent Change From Baseline in Body Weight at 24 Weeks [Baseline, Week 24 (Epoch 3)]

    Dose-response relationship of two dose regimens of LIK066 as measured by the percent change from baseline in body weight relative to placebo after 24 weeks of treatment

Secondary Outcome Measures

  1. Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study [Baseline, Week 24]

    Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline

  2. Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups [Baseline, Week 24]

    Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline for dysglycemic, normoglycemic, Type 2 Diabetes Mellitus (T2DM)

  3. Percentage Change From Baseline on Waist Circumference [Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)]

    Waist circumference will be measured to the nearest 0.1cm in a standing position, at the end of a normal expiration, using a tape at the level of the iliac crest.

  4. Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) [Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)]

    FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake).

  5. Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) [Baseline, Week 24 (Epoch 3), Week 24 to week 48 (Epoch 4)]

    HbA1c will be measured from a blood sample obtained at indicated visits and will be analyzed at a central laboratory.

  6. Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) [Baseline, Week 24 (Epoch 3) Week 24 to Week 48 (Epoch 4)]

    At each study visit (baseline, week 24, Week 48), after the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP and DBP will be measured

  7. Change From Baseline in 24-hour Urinary Glucose Excretion [Baseline, week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)]

    Urinary glucose excretion will be measured from 24-hour urinary collection at indicated visits and will be analyzed at a central laboratory.

  8. Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4) [Between Week 24 and Week 48 (Epoch 4)]

    Between -treatment analysis of percentage change from Week 24 in body weight (kg) at Week 48 (Epoch 4)

  9. Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion [Baseline, Week 24]

    Evaluation of 24-hour urinary calcium excretion after 24 week of treatment.

  10. Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion [Baseline, Week 24, Week 48]

    Evaluation of 24-hour urinary calcium after 48 weeks of treatment

  11. Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion [Week 24, Week 48]

    Evaluation of 24-hour urinary phosphorus excretion after 24 weeks of treatment

  12. Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion [Week 24, Week 48]

    Evaluation of 24-hour urinary phosphorus excretion after 48 weeks of treatment

  13. Change From Baseline in Fasting Lipid Profile (Lipoproteins) [Baseline, Week 24, Week 24 to Week 48 (Epoch 4)]

    Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48

  14. Change From Baseline in High Sensitive C-reactive Protein (hsCRP) [Baseline to Week 24, Week 24 to Week 48 (Epoch 4)]

    Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48

  15. Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) [Baseline to Week 24, Week 24 to Week 48 (Epoch 4)]

    Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48

  16. Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) [Summary at Week 24 from qd or bid regimens]

    Observe maximum plasma concentration following administration of LIK066 (Cmax)

  17. Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) [Summary at Week 24 for qd or bid regimens]

    Time to reach the maximum concentration after administration of LIK066 (Tmax)

  18. Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) [Summary at Week 24 from qd or bid regimens (0-6h)]

    Area under the plasma concentration-time curve from time zero time 't' where t is a defined time point after administration (AUC0-t)

  19. Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) [Summary at Week 24 from qd or bid regimens]

    Last non-zero concentration area under the curve (AUClast)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. informed consent

  2. (BMI>=30) or (BMI>=27 with history of CV disease, hypertension, dyslipidemia, pre-diabetes or type 2 diabetes mellitus, sleep-apnea syndrome)

  3. willing to comply with life-style intervention and treatment during the full duration of the study (approximately 54 weeks)

Exclusion Criteria:

  • Hypersensitivity to any of the study medications

  • Pregnancy or lactating women

  • History of malignancies

  • Use of pharmacologically active weight loss products

  • Bariatric surgery

  • Ketoacidosis, lactic acidosis, hyperosmolar coma in the 6 months before the screening visit.

  • HbA1c >10% at the screening visit.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Novartis Investigative Site Anniston Alabama United States 36207
2 Novartis Investigative Site Jasper Alabama United States 35501
3 Novartis Investigative Site Beverly Hills California United States 90211
4 Novartis Investigative Site Carmichael California United States 95608
5 Novartis Investigative Site Concord California United States 94520
6 Novartis Investigative Site Los Angeles California United States 90017
7 Novartis Investigative Site Northridge California United States 91325
8 Novartis Investigative Site Roseville California United States 95661
9 Novartis Investigative Site San Ramon California United States 94582
10 Novartis Investigative Site Stockton California United States 95204
11 Novartis Investigative Site Walnut Creek California United States 94598
12 Novartis Investigative Site Denver Colorado United States 80246
13 Novartis Investigative Site Golden Colorado United States 80401
14 Novartis Investigative Site Bradenton Florida United States 34209
15 Novartis Investigative Site Fort Lauderdale Florida United States 33312
16 Novartis Investigative Site Port Charlotte Florida United States 33952
17 Novartis Investigative Site West Palm Beach Florida United States 33401
18 Novartis Investigative Site Athens Georgia United States 30606
19 Novartis Investigative Site Augusta Georgia United States 30909
20 Novartis Investigative Site Honolulu Hawaii United States 96814
21 Novartis Investigative Site Gurnee Illinois United States 60031
22 Novartis Investigative Site Springfield Illinois United States 62711
23 Novartis Investigative Site Wauconda Illinois United States 60084
24 Novartis Investigative Site Evansville Indiana United States 47713
25 Novartis Investigative Site Evansville Indiana United States 47714
26 Novartis Investigative Site Indianapolis Indiana United States 46260
27 Novartis Investigative Site Louisville Kentucky United States 40213
28 Novartis Investigative Site Baton Rouge Louisiana United States 70808
29 Novartis Investigative Site Covington Louisiana United States 70433
30 Novartis Investigative Site Hammond Louisiana United States 70403
31 Novartis Investigative Site Metairie Louisiana United States 70006
32 Novartis Investigative Site New Orleans Louisiana United States 70115
33 Novartis Investigative Site New Orleans Louisiana United States 70119
34 Novartis Investigative Site Baltimore Maryland United States 21229
35 Novartis Investigative Site Beltsville Maryland United States 20705
36 Novartis Investigative Site Towson Maryland United States 21204
37 Novartis Investigative Site Royal Oak Michigan United States 48073
38 Novartis Investigative Site Saint Louis Missouri United States 63128
39 Novartis Investigative Site Saint Peters Missouri United States 63303
40 Novartis Investigative Site Missoula Montana United States 59808
41 Novartis Investigative Site Omaha Nebraska United States 68134
42 Novartis Investigative Site Bronx New York United States 10455
43 Novartis Investigative Site New York New York United States 10016
44 Novartis Investigative Site New York New York United States 10021
45 Novartis Investigative Site Hickory North Carolina United States 28601
46 Novartis Investigative Site Lansdale Pennsylvania United States 19446
47 Novartis Investigative Site Pittsburgh Pennsylvania United States 15212
48 Novartis Investigative Site Moncks Corner South Carolina United States 29464
49 Novartis Investigative Site Mount Pleasant South Carolina United States 29464
50 Novartis Investigative Site Summerville South Carolina United States 29485
51 Novartis Investigative Site Houston Texas United States 77081
52 Novartis Investigative Site Bountiful Utah United States 84010
53 Novartis Investigative Site Salt Lake City Utah United States 84102
54 Novartis Investigative Site Newport News Virginia United States 23606
55 Novartis Investigative Site Richmond Virginia United States 23235
56 Novartis Investigative Site Richmond Virginia United States 23294
57 Novartis Investigative Site Renton Washington United States 98057
58 Novartis Investigative Site Tacoma Washington United States 98405
59 Novartis Investigative Site Kenosha Wisconsin United States 53144
60 Novartis Investigative Site Graz Austria 8036
61 Novartis Investigative Site Wien Austria 1010
62 Novartis Investigative Site Wien Austria 1030
63 Novartis Investigative Site Toronto Ontario Canada M4G 3E8
64 Novartis Investigative Site Toronto Ontario Canada M9W 4L6
65 Novartis Investigative Site Gatineau Quebec Canada J8Y 6S8
66 Novartis Investigative Site Levis Quebec Canada G6W 5M6
67 Novartis Investigative Site Praha 2 Czech Republic Czechia 128 08
68 Novartis Investigative Site Ceske Budejovice Czechia 370 01
69 Novartis Investigative Site Olomouc Lazce Czechia 77900
70 Novartis Investigative Site Praha 1 Czechia 116 94
71 Novartis Investigative Site Praha 3 Czechia 13000
72 Novartis Investigative Site Slany Czechia 274 01
73 Novartis Investigative Site Csongrad Hungary 6640
74 Novartis Investigative Site Nyiregyhaza Hungary 4400
75 Novartis Investigative Site Szentes Hungary 6600
76 Novartis Investigative Site Bratislava Slovakia 85101
77 Novartis Investigative Site Kosice Slovakia 040 01
78 Novartis Investigative Site Sered Slovakia 92601
79 Novartis Investigative Site Basingstoke United Kingdom RG24 9DT
80 Novartis Investigative Site Blackburn United Kingdom BB2 1AX
81 Novartis Investigative Site Exeter United Kingdom EX2 5DW
82 Novartis Investigative Site Rotherham United Kingdom S65 1DA
83 Novartis Investigative Site Stevenage United Kingdom SG1 4AB

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03100058
Other Study ID Numbers:
  • CLIK066B2201
  • 2016-002868-14
First Posted:
Apr 4, 2017
Last Update Posted:
Feb 6, 2020
Last Verified:
Jan 1, 2020
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
Obesity
Overweight
Additional relevant MeSH terms:
Overweight
Licogliflozin

Study Results

Participant Flow

Recruitment Details Overall, 674 patients were screened. Of the 460 patients who were randomized to the study, the majority (85.7%) completed Epoch 3. Of the 394 patients who completed Epoch 3 and entered Epoch 4, the majority (93.1%) completed the Epoch 4 study period.
Pre-assignment Detail Overall, 674 patients were screened. Of the 460 patients who were randomized to the study, the majority (85.7%) completed Epoch 3. Of the 394 patients who completed Epoch 3 and entered Epoch 4, the majority (93.1%) completed the Epoch 4 study period.
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25 mg qd (Epoch 4) LIK066 Bid/LIK066 35 mg qd (Epoch 4) Placebo/LIK066 25 mg qd (Epoch 4) Placebo qd (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks LIK066 qd (once daily) patients who entered Epoch 4 and received LIK066 25 mg qd LIK066 bid patients who entered Epoch 4 and received LIK066 35 mg qd Matching placebo tablets for 24 weeks Placebo patients who entered Epoch 4 and received matching Placebo tablets qd
Period Title: Epoch 3 (24 Weeks of Treatment)
STARTED 38 38 38 77 38 39 38 76 78 0 0 0 0
COMPLETED 35 31 29 63 36 37 30 60 73 0 0 0 0
NOT COMPLETED 3 7 9 14 2 2 8 16 5 0 0 0 0
Period Title: Epoch 3 (24 Weeks of Treatment)
STARTED 0 0 0 0 0 0 0 0 0 158 163 39 34
COMPLETED 0 0 0 0 0 0 0 0 0 153 148 36 30
NOT COMPLETED 0 0 0 0 0 0 0 0 0 5 15 3 4

Baseline Characteristics

Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) Total
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Total of all reporting groups
Overall Participants 38 38 38 77 38 39 38 76 78 460
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
51.3
(12.20)
53.2
(10.08)
52.9
(13.60)
51.1
(12.94)
53.4
(12.28)
49.8
(11.50)
49.7
(11.93)
52.9
(11.87)
51.1
(13.27)
51.7
(12.31)
Sex: Female, Male (Count of Participants)
Female
23
60.5%
27
71.1%
25
65.8%
44
57.1%
20
52.6%
24
61.5%
26
68.4%
49
64.5%
45
57.7%
283
61.5%
Male
15
39.5%
11
28.9%
13
34.2%
33
42.9%
18
47.4%
15
38.5%
12
31.6%
27
35.5%
33
42.3%
177
38.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
2
5.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
2
2.6%
2
2.6%
6
1.3%
Asian
0
0%
0
0%
0
0%
2
2.6%
0
0%
2
5.1%
0
0%
5
6.6%
1
1.3%
10
2.2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
2
2.6%
0
0%
0
0%
0
0%
0
0%
1
1.3%
3
0.7%
Black or African American
5
13.2%
4
10.5%
5
13.2%
5
6.5%
2
5.3%
3
7.7%
4
10.5%
6
7.9%
8
10.3%
42
9.1%
White
30
78.9%
33
86.8%
33
86.8%
67
87%
36
94.7%
32
82.1%
34
89.5%
63
82.9%
64
82.1%
392
85.2%
More than one race
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
1
2.6%
1
2.6%
0
0%
1
1.3%
0
0%
2
5.1%
0
0%
0
0%
2
2.6%
7
1.5%

Outcome Measures

1. Primary Outcome
Title Percent Change From Baseline in Body Weight at 24 Weeks
Description Dose-response relationship of two dose regimens of LIK066 as measured by the percent change from baseline in body weight relative to placebo after 24 weeks of treatment
Time Frame Baseline, Week 24 (Epoch 3)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks
Measure Participants 38 38 38 77 38 39 38 76 78
Mean (95% Confidence Interval) [Percent change]
-1.24
-2.04
-3.52
-4.37
-1.67
-2.51
-4.06
-4.47
-0.63
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.73
Confidence Interval (2-Sided) 95%
-3.17 to -0.29
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.93
Confidence Interval (2-Sided) 95%
-3.36 to -0.50
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.30
Confidence Interval (2-Sided) 95%
-4.86 to -1.75
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.42
Confidence Interval (2-Sided) 95%
-5.39 to -3.44
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.14
Confidence Interval (2-Sided) 95%
-2.53 to -0.25
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.74
Confidence Interval (2-Sided) 95%
-4.11 to -1.36
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.11
Confidence Interval (2-Sided) 95%
-5.54 to -2.68
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.48
Confidence Interval (2-Sided) 95%
-5.54 to -3.43
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study
Description Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline
Time Frame Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks
Measure Participants 38 38 38 77 38 39 37 75 78
>=5%
26.3
15.8
34.2
42.9
15.8
20.5
37.8
45.3
12.8
>=10%
5.3
5.3
5.3
6.5
5.3
2.6
10.8
9.3
3.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.099
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.38
Confidence Interval (2-Sided) 95%
0.85 to 6.67
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.779
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.36 to 3.84
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.011
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.69
Confidence Interval (2-Sided) 95%
1.35 to 10.11
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.57
Confidence Interval (2-Sided) 95%
2.41 to 12.88
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.812
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.36 to 3.74
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.229
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.94
Confidence Interval (2-Sided) 95%
0.66 to 5.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.004
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.29
Confidence Interval (2-Sided) 95%
1.61 to 11.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.37
Confidence Interval (2-Sided) 95%
2.72 to 14.93
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.943
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.10 to 12.41
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.465
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.11
Confidence Interval (2-Sided) 95%
0.28 to 15.77
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.696
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.60
Confidence Interval (2-Sided) 95%
0.15 to 17.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.389
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.14
Confidence Interval (2-Sided) 95%
0.38 to 12.10
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.976
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.09 to 11.87
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.986
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.09 to 11.70
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.181
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.51
Confidence Interval (2-Sided) 95%
0.56 to 22.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=10%
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.100
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.97
Confidence Interval (2-Sided) 95%
0.77 to 20.54
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups
Description Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline for dysglycemic, normoglycemic, Type 2 Diabetes Mellitus (T2DM)
Time Frame Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks
Measure Participants 38 38 38 77 38 39 37 75 78
Dysglycemic (>=5%)
31.3
25.0
40.0
48.4
6.7
37.5
40.0
41.9
9.7
Normoglycemic (>=5%)
44.4
11.1
44.4
47.4
11.1
11.1
55.6
52.9
20.0
Type 2 Diabetes Mellitus (T2DM) (>=5%)
7.7
15.4
28.6
37.0
28.6
14.3
30.8
44.4
14.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dysglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.048
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.29
Confidence Interval (2-Sided) 95%
1.02 to 38.76
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dsyglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.171
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 3.94
Confidence Interval (2-Sided) 95%
0.55 to 28.03
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dysglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.041
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.17
Confidence Interval (2-Sided) 95%
1.09 to 47.27
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dysglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.003
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.89
Confidence Interval (2-Sided) 95%
2.32 to 60.93
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dysglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.976
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.08 to 11.72
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dysglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.022
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.78
Confidence Interval (2-Sided) 95%
1.37 to 56.44
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dysglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.032
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.50
Confidence Interval (2-Sided) 95%
1.20 to 46.99
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Dysglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.005
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.28
Confidence Interval (2-Sided) 95%
2.11 to 60.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.227
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.21
Confidence Interval (2-Sided) 95%
0.48 to 21.28
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.763
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.06 to 7.85
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.095
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.68
Confidence Interval (2-Sided) 95%
0.76 to 28.70
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.033
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.33
Confidence Interval (2-Sided) 95%
1.14 to 24.83
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.788
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.06 to 8.10
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.751
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.06 to 7.62
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.027
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.05
Confidence Interval (2-Sided) 95%
1.27 to 51.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (Normoglycemic)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.023
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.64
Confidence Interval (2-Sided) 95%
1.30 to 34.00
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.528
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.05 to 4.78
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.958
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.17 to 6.68
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.546
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
0.30 to 9.49
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding test
Statistical Test of Hypothesis p-Value 0.098
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.09
Confidence Interval (2-Sided) 95%
0.81 to 11.75
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.563
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
0.31 to 8.70
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.610
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.06 to 5.38
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.528
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.71
Confidence Interval (2-Sided) 95%
0.32 to 9.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments >=5% (T2DM)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.023
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.55
Confidence Interval (2-Sided) 95%
1.23 to 16.90
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Percentage Change From Baseline on Waist Circumference
Description Waist circumference will be measured to the nearest 0.1cm in a standing position, at the end of a normal expiration, using a tape at the level of the iliac crest.
Time Frame Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
Mean (95% Confidence Interval) [Percentage Change]
-2.1
-2.7
-3.7
-5.6
-2.7
-4.3
-4.8
-4.6
-1.3
-0.4
-0.7
-2.1
0.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.470
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.96 to 1.37
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.199
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-3.64 to 0.76
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-3.64 to 0.76
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.206
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-3.56 to 0.77
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.006
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-5.18 to -0.88
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.002
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-5.70 to -1.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-5.10 to -1.51
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 qd/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.391
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.82 to 1.10
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LIK066 Bid/LIK066 35mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.259
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-3.10 to 0.84
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.048
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-4.91 to -0.02
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM)
Description FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake).
Time Frame Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
Mean (95% Confidence Interval) [mmol/L]
1.9
-0.1
-1.2
-0.8
-0.5
-1.1
-0.9
-1.0
0.9
-0.1
-0.3
-0.1
0.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.225
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-0.62 to 2.61
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.247
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-2.62 to 0.68
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.019
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-3.75 to -0.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.015
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-2.96 to -0.33
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.106
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.97 to 0.29
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.020
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.54 to -0.31
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.035
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.44 to -0.12
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.004
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.22 to -0.61
Parameter Dispersion Type:
Value:
Estimation Comments
6. Secondary Outcome
Title Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM)
Description HbA1c will be measured from a blood sample obtained at indicated visits and will be analyzed at a central laboratory.
Time Frame Baseline, Week 24 (Epoch 3), Week 24 to week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
Mean (95% Confidence Interval) [mmol/L]
0.1
-0.5
-0.9
-0.7
-0.3
-0.5
-0.6
-0.6
-0.3
0.2
0.0
-0.1
0.3
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.082
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.05 to 0.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.319
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.63 to 0.21
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.008
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.05 to -0.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.015
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.76 to -0.08
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.707
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.50 to 0.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.280
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.65 to 0.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.086
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.80 to 0.05
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.030
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.72 to -0.04
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP)
Description At each study visit (baseline, week 24, Week 48), after the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP and DBP will be measured
Time Frame Baseline, Week 24 (Epoch 3) Week 24 to Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
systolic blood pressure (SBP)
-1.2
-1.5
-4.9
-1.2
-0.7
0.8
-2.6
-1.8
1.6
-0.9
-1.6
-5.6
0.8
diastolic blood pressure (DBP)
-0.2
0.1
-2.3
-1.3
0.8
-1.4
0.3
-1.7
0.5
-0.6
-1.2
-2.0
0.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.156
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-6.64 to 1.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.127
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-7.11 to 0.89
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.002
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.5
Confidence Interval (2-Sided) 95%
-10.52 to -2.42
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.089
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-5.86 to 0.42
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.245
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-6.12 to 1.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.678
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-4.65 to 3.02
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.040
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-8.07 to -0.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments SBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.038
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-6.61 to -0.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.601
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-3.38 to 1.96
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.760
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-3.20 to 2.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.051
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-5.60 to 0.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.105
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.98 to 0.38
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.820
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-2.36 to 2.98
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.157
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-4.58 to 0.74
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.859
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-2.99 to 2.49
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments DBP
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.054
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-4.41 to 0.04
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Change From Baseline in 24-hour Urinary Glucose Excretion
Description Urinary glucose excretion will be measured from 24-hour urinary collection at indicated visits and will be analyzed at a central laboratory.
Time Frame Baseline, week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
Mean (95% Confidence Interval) [mmol/24hr]
208.6
134.6
377.0
306.1
183.0
193.8
241.3
308.9
-17.8
26.8
122.5
248.0
-148.9
9. Secondary Outcome
Title Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4)
Description Between -treatment analysis of percentage change from Week 24 in body weight (kg) at Week 48 (Epoch 4)
Time Frame Between Week 24 and Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 158 163 39 34
Mean (95% Confidence Interval) [Percentage]
-0.2
-0.2
-2.4
0.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), LIK066 150mg qd (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.355
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.84 to 0.66
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), LIK066 150mg qd (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.373
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.83 to 0.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), LIK066 150mg qd (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-4.36 to -1.24
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion
Description Evaluation of 24-hour urinary calcium excretion after 24 week of treatment.
Time Frame Baseline, Week 24

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks
Measure Participants 38 38 38 77 38 39 38 76 78
Baseline
49.6
(25.08)
33.1
(29.65)
40.2
(21.55)
34.6
(17.56)
44.7
(26.83)
43.6
(16.91)
38.0
(22.13)
47.9
(23.64)
43.0
(22.63)
Week 24 (Timepoint 1)
48.8
(26.59)
38.1
(32.20)
39.8
(22.48)
40.1
(18.20)
52.4
(32.78)
45.9
(15.41)
38.0
(22.13)
48.1
(21.93)
44.7
(23.0)
Week 24 (Timepoint 2)
54.2
(29.34)
42.0
(29.99)
39.2
(20.24)
62.8
(34.26)
51.2
(35.32)
54.6
(23.77)
37.9
(32.33)
53.0
(26.95)
52.2
(30.75)
Week 24 (Timepoint 3)
5.4
(22.74)
3.9
(19.56)
-0.6
(12.07)
22.8
(28.42)
-1.2
(7.77)
8.7
(18.21)
-0.1
(14.39)
4.9
(26.20)
7.5
(32.91)
11. Secondary Outcome
Title Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion
Description Evaluation of 24-hour urinary calcium after 48 weeks of treatment
Time Frame Baseline, Week 24, Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 158 163 39 34
Baseline
4.8
(3.02)
5.0
(2.84)
4.6
(0.91)
5.6
(4.07)
Week 48(Timepoint 1)
5.1
(307)
5.2
(2.95)
4.5
(0.95)
6.6
(4.55)
Week 48(Timepoint 2)
4.6
(2.33)
5.6
(4.55)
5.4
(3.65)
4.8
(2.10)
Week 48(Timepoint 3)
-0.5
(3.41)
0.4
(2.81)
0.9
(4.10)
-1.8
(3.26)
12. Secondary Outcome
Title Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion
Description Evaluation of 24-hour urinary phosphorus excretion after 24 weeks of treatment
Time Frame Week 24, Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks
Measure Participants 38 38 38 77 38 39 38 76 78
Baseline
282.1
(128.10)
240.5
(74.64)
254.5
(105.70)
291.5
(175.10)
284.0
(117.60)
241.8
(82.75)
277.0
(99.67)
293.7
(120.70)
297.0
(145.10)
Week 24 (Timepoint 1)
284.0
(140.10)
239.7
(80.40)
260.9
(111.10)
275.0
(101.30)
319.9
(32.78)
246.5
(84.19)
299.3
(79.06)
302.5
(121.30)
307.9
(145.90)
Week 24 (Timepoint 2)
297.7
(117.40)
295.3
(95.60)
299.2
(145.50)
264.7
(74.84)
317.8
(205.10)
341.6
(109.20)
260.5
(124.80)
289.3
(83.62)
352.8
(159.30)
Week 24 (Timepoint 3)
13.0
(132.00)
55.6
(89.81)
38.3
(70.00)
-10.2
(103.60)
-2.1
(159.60)
95.1
(67.36)
-38.7
(107.80)
-13.2
(153.80)
44.9
(177.60)
13. Secondary Outcome
Title Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion
Description Evaluation of 24-hour urinary phosphorus excretion after 48 weeks of treatment
Time Frame Week 24, Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 158 163 39 34
Baseline
27.6
(11.46)
30.5
(11.63)
28.6
(14.11)
40.2
(15.96)
Week 48 (Timepoint 1)
27.5
(11.73)
30.2
(11.85)
28.6
(14.11)
44.4
(17.60)
Week 48 (Timepoint 2)
24.7
(12.74)
31.1
(16.21)
31.0
(14.67)
29.0
(15.42)
Week 48(Timepoint 3)
-2.8
(11.44)
0.9
(14.52)
2.4
(17.33)
-15.5
(18.92)
14. Secondary Outcome
Title Change From Baseline in Fasting Lipid Profile (Lipoproteins)
Description Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48
Time Frame Baseline, Week 24, Week 24 to Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
Apoliprotein A1
8.9
8.13
10.7
8.9
5.3
8.1
6.7
11.0
6.7
3.0
3.4
5.6
-0.7
Apoliprotein B
2.9
7.7
3.3
12.4
-0.4
4.5
2.3
3.9
5.8
-1.7
-2.4
-2.3
-2.0
15. Secondary Outcome
Title Change From Baseline in High Sensitive C-reactive Protein (hsCRP)
Description Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48
Time Frame Baseline to Week 24, Week 24 to Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
Geometric Mean (95% Confidence Interval) [mg/L]
0.99
1.06
1.31
0.98
1.02
0.93
1.00
0.98
0.92
0.95
0.93
0.96
1.07
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.632
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.81 to 1.42
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.352
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.86 to 1.55
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.027
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
1.04 to 1.92
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.587
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.85 to 1.35
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.508
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.82 to 1.47
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.945
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.76 to 1.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.602
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.81 to 1.45
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.612
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.84 to 1.35
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LIK066 qd/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.382
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.68 to 1.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LIK066 Bid/LIK066 35mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.310
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.67 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.525
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.65 to 1.25
Parameter Dispersion Type:
Value:
Estimation Comments
16. Secondary Outcome
Title Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol)
Description Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48
Time Frame Baseline to Week 24, Week 24 to Week 48 (Epoch 4)

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3) Placebo (Epoch 3) LIK066 qd/LIK066 25mg qd (Epoch 4) LIK066 Bid/LIK066 35mg qd (Epoch 4) Placebo/LIK066 25mg qd (Epoch 4) Placebo/Placebo (Epoch 4)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily Between week 24 to week 48, the patients who received a once daily regimen in the first 24 weeks will receive Dose A of LIK066 once daily and patients who received a twice daily regimen in the first 24 weeks will receive Dose B LIK066 once daily
Measure Participants 38 38 38 77 38 39 38 76 78 158 163 39 34
Triglycerides (TG)
-3.8
1.3
-11.5
-3.0
2.3
1.7
5.5
-7.4
4.0
6.7
12.4
-0.9
4.8
Total Cholesterol (TC)
6.0
7.3
4.8
14.6
1.5
5.1
6.4
8.8
4.7
0.8
0.3
0.8
-1.7
HDL Cholesterol
0.8
4.9
5.2
8.0
2.9
2.4
1.5
8.0
0.7
3.9
3.7
9.2
0.7
LDL Cholesterol
8.7
17.5
8.2
21.8
4.1
8.7
7.7
10.9
12.5
-0.6
-1.2
-1.4
-3.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.254
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -7.9
Confidence Interval (2-Sided) 95%
-21.37 to 5.65
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.716
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-17.44 to 11.99
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.038
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15.6
Confidence Interval (2-Sided) 95%
-30.30 to -0.86
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.213
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -7.0
Confidence Interval (2-Sided) 95%
-18.15 to 4.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.806
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-15.38 to 11.96
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.739
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-15.80 to 11.21
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.837
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-12.36 to 15.26
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.049
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -11.4
Confidence Interval (2-Sided) 95%
-22.71 to -0.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.764
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-7.22 to 9.82
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.571
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-6.43 to 11.63
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.987
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-9.30 to 9.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.006
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.9
Confidence Interval (2-Sided) 95%
2.85 to 16.87
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.463
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-12.03 to 5.48
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.925
Comments
Method ANOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-8.18 to 9.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.711
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-7.19 to 10.53
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.265
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
-3.10 to 11.26
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.995
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-7.31 to 7.36
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.288
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
-3.52 to 11.81
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.269
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.5
Confidence Interval (2-Sided) 95%
-3.50 to 12.50
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.018
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
1.23 to 13.27
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.565
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-5.32 to 9.73
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.649
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-5.67 to 9.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.847
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-6.87 to 8.36
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.020
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
1.14 to 13.43
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg qd (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.579
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-17.09 to 9.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection LIK066 10mg qd (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.487
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-9.08 to 19.02
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection LIK066 50mg qd (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.561
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.3
Confidence Interval (2-Sided) 95%
-18.96 to 10.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection LIK066 150mg qd (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.097
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.3
Confidence Interval (2-Sided) 95%
-1.68 to 20.25
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection LIK066 2.5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.227
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.4
Confidence Interval (2-Sided) 95%
-22.10 to 5.26
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection LIK066 5mg Bid (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.580
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-17.22 to 9.64
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection LIK066 25mg Bid (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.494
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-18.67 to 9.03
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection LIK066 50mg Bid (Epoch 3), Placebo (Epoch 3)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.782
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-12.81 to 9.65
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection LIK066 qd/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.816
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-13.82 to 17.54
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection LIK066 Bid/LIK066 35mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.341
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.02
Confidence Interval (2-Sided) 95%
-8.13 to 23.42
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Placebo/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments Triglycerides (TG)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.566
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 9.99
Confidence Interval (2-Sided) 95%
-25.39 to 13.91
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection LIK066 qd/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.405
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.98
Confidence Interval (2-Sided) 95%
-3.38 to 8.36
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection LIK066 Bid/LIK066 35mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.511
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-3.92 to 7.87
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Placebo/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments Total Cholesterol (TC)
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.506
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
-4.83 to 9.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection LIK066 qd/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.392
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
-4.20 to 10.70
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection LIK066 Bid/LIK066 35mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.426
Comments
Method ANOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-4.45 to 10.53
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Placebo/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments HDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.071
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.5
Confidence Interval (2-Sided) 95%
-0.72 to 17.80
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection LIK066 qd/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.498
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-5.56 to 11.42
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection LIK066 Bid/LIK066 35mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.586
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
-6.17 to 10.90
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Placebo/LIK066 25mg qd (Epoch 4), Placebo/Placebo (Epoch 4)
Comments LDL Cholesterol
Type of Statistical Test Other
Comments Dose finding study
Statistical Test of Hypothesis p-Value 0.696
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-8.47 to 12.67
Parameter Dispersion Type:
Value:
Estimation Comments
17. Secondary Outcome
Title Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax)
Description Observe maximum plasma concentration following administration of LIK066 (Cmax)
Time Frame Summary at Week 24 from qd or bid regimens

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks
Measure Participants 38 38 38 77 38 39 37 76
Mean (Standard Deviation) [ng/mL]
80.0
(97.2)
128
(00.0)
798
(397)
1810
(545)
38.6
(5.22)
84.2
(19.0)
523
(118)
811
(367)
18. Secondary Outcome
Title Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax)
Description Time to reach the maximum concentration after administration of LIK066 (Tmax)
Time Frame Summary at Week 24 for qd or bid regimens

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks
Measure Participants 38 38 38 77 38 39 37 76
Median (Full Range) [hour]
1.00
1.00
1.01
1.02
1.00
1.00
0.992
1.00
19. Secondary Outcome
Title Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t)
Description Area under the plasma concentration-time curve from time zero time 't' where t is a defined time point after administration (AUC0-t)
Time Frame Summary at Week 24 from qd or bid regimens (0-6h)

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks
Measure Participants 38 38 38 77 38 39 37 76
Mean (Standard Deviation) [hr*ng/mL]
196
(186)
275
(000)
2280
(522)
5700
(1490)
105
(17.1)
273
(69.3)
1520
(277)
2190
(841)
20. Secondary Outcome
Title Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast)
Description Last non-zero concentration area under the curve (AUClast)
Time Frame Summary at Week 24 from qd or bid regimens

Outcome Measure Data

Analysis Population Description
Full Analysis Set
Arm/Group Title LIK066 2.5mg qd (Epoch 3) LIK066 10mg qd (Epoch 3) LIK066 50mg qd (Epoch 3) LIK066 150mg qd (Epoch 3) LIK066 2.5mg Bid (Epoch 3) LIK066 5mg Bid (Epoch 3) LIK066 25mg Bid (Epoch 3) LIK066 50mg Bid (Epoch 3)
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks
Measure Participants 38 38 38 77 38 39 37 76
Mean (Standard Deviation) [hr*ng/mL]
196
(186)
275
(000)
2290
(526)
5690
(1480)
105
(17.2)
273
(70.2)
1520
(271)
2190
(843)

Adverse Events

Time Frame Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 15 months.
Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Arm/Group Title LIK066 2.5 mg qd (Epoch 3)/25 mg qd (Epoch 4) LIK066 10 mg qd/25 mg qd LIK066 50 mg qd/25 mg qd LIK066 150 mg qd/25 mg qd LIK066 2.5 mg Bid/35 mg qd LIK066 5 mg Bid/35 mg qd LIK066 25 mg Bid/35 mg qd LIK066 50 mg Bid/35 mg qd Placebo/LIK066 25 mg qd (Epoch 4) Placebo/Placebo
Arm/Group Description LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks (Epoch3), then LIK066 25 mg qd for 24 weeks (Epoch 4) LIK066 10mg qd (once daily) dosing frequency for 24 weeks LIK066 50mg qd (once daily) dosing frequency for 24 weeks LIK066 150mg qd (once daily) dosing frequency for 24 weeks LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks LIK066 5mg bid (twice daily) dosing frequency for 24 weeks LIK066 25mg bid (twice daily) dosing frequency for 24 weeks LIK066 50mg bid (twice daily) dosing frequency for 24 weeks Matching placebo tablets for 24 weeks Matching placebo tablets
All Cause Mortality
LIK066 2.5 mg qd (Epoch 3)/25 mg qd (Epoch 4) LIK066 10 mg qd/25 mg qd LIK066 50 mg qd/25 mg qd LIK066 150 mg qd/25 mg qd LIK066 2.5 mg Bid/35 mg qd LIK066 5 mg Bid/35 mg qd LIK066 25 mg Bid/35 mg qd LIK066 50 mg Bid/35 mg qd Placebo/LIK066 25 mg qd (Epoch 4) Placebo/Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Serious Adverse Events
LIK066 2.5 mg qd (Epoch 3)/25 mg qd (Epoch 4) LIK066 10 mg qd/25 mg qd LIK066 50 mg qd/25 mg qd LIK066 150 mg qd/25 mg qd LIK066 2.5 mg Bid/35 mg qd LIK066 5 mg Bid/35 mg qd LIK066 25 mg Bid/35 mg qd LIK066 50 mg Bid/35 mg qd Placebo/LIK066 25 mg qd (Epoch 4) Placebo/Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/38 (7.9%) 3/38 (7.9%) 1/38 (2.6%) 3/77 (3.9%) 5/38 (13.2%) 2/39 (5.1%) 2/38 (5.3%) 1/76 (1.3%) 1/40 (2.5%) 4/38 (10.5%)
Blood and lymphatic system disorders
Anaemia 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Cardiac disorders
Acute myocardial infarction 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Angina pectoris 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Atrial fibrillation 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Myocardial infarction 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Gastrointestinal disorders
Abdominal pain lower 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Abdominal pain upper 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Duodenal ulcer 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Obstructive pancreatitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Pancreatitis acute 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hepatobiliary disorders
Bile duct stone 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Cholecystitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Cholecystitis acute 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Cholelithiasis 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Infections and infestations
Diverticulitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Erysipelas 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Leiomyosarcoma 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Uterine leiomyoma 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Reproductive system and breast disorders
Breast enlargement 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Dysmenorrhoea 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Dyspareunia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Endometrial hyperplasia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Menorrhagia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Vascular disorders
Circulatory collapse 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Deep vein thrombosis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hypertension 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Peripheral arterial occlusive disease 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Other (Not Including Serious) Adverse Events
LIK066 2.5 mg qd (Epoch 3)/25 mg qd (Epoch 4) LIK066 10 mg qd/25 mg qd LIK066 50 mg qd/25 mg qd LIK066 150 mg qd/25 mg qd LIK066 2.5 mg Bid/35 mg qd LIK066 5 mg Bid/35 mg qd LIK066 25 mg Bid/35 mg qd LIK066 50 mg Bid/35 mg qd Placebo/LIK066 25 mg qd (Epoch 4) Placebo/Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 33/38 (86.8%) 24/38 (63.2%) 24/38 (63.2%) 55/77 (71.4%) 31/38 (81.6%) 32/39 (82.1%) 26/38 (68.4%) 47/76 (61.8%) 32/40 (80%) 32/38 (84.2%)
Blood and lymphatic system disorders
Anaemia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Iron deficiency anaemia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Neutropenia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Polycythaemia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Thrombocytopenia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Thrombocytosis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Cardiac disorders
Atrial fibrillation 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Bundle branch block right 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Microvascular coronary artery disease 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Sinus tachycardia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Congenital, familial and genetic disorders
Porokeratosis 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Type IIa hyperlipidaemia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Ear and labyrinth disorders
Ear pain 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Eustachian tube dysfunction 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Inner ear disorder 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Tympanic membrane perforation 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vertigo 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 2/39 (5.1%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 1/38 (2.6%)
Vertigo positional 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Endocrine disorders
Hypothyroidism 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Eye disorders
Blepharospasm 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Cataract 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 2/38 (5.3%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Dry eye 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Eye movement disorder 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Eye pruritus 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Myopic chorioretinal degeneration 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Ulcerative keratitis 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Visual impairment 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vitreous floaters 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Gastrointestinal disorders
Abdominal discomfort 1/38 (2.6%) 1/38 (2.6%) 3/38 (7.9%) 7/77 (9.1%) 3/38 (7.9%) 3/39 (7.7%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 4/38 (10.5%)
Abdominal distension 3/38 (7.9%) 2/38 (5.3%) 4/38 (10.5%) 8/77 (10.4%) 9/38 (23.7%) 5/39 (12.8%) 4/38 (10.5%) 6/76 (7.9%) 6/40 (15%) 7/38 (18.4%)
Abdominal pain 2/38 (5.3%) 1/38 (2.6%) 2/38 (5.3%) 3/77 (3.9%) 1/38 (2.6%) 3/39 (7.7%) 2/38 (5.3%) 2/76 (2.6%) 1/40 (2.5%) 4/38 (10.5%)
Abdominal pain lower 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Abdominal pain upper 2/38 (5.3%) 3/38 (7.9%) 4/38 (10.5%) 7/77 (9.1%) 7/38 (18.4%) 3/39 (7.7%) 4/38 (10.5%) 4/76 (5.3%) 4/40 (10%) 4/38 (10.5%)
Bowel movement irregularity 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Breath odour 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Change of bowel habit 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 3/77 (3.9%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Chronic gastritis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Constipation 6/38 (15.8%) 7/38 (18.4%) 6/38 (15.8%) 11/77 (14.3%) 12/38 (31.6%) 5/39 (12.8%) 8/38 (21.1%) 8/76 (10.5%) 7/40 (17.5%) 9/38 (23.7%)
Defaecation urgency 0/38 (0%) 0/38 (0%) 4/38 (10.5%) 7/77 (9.1%) 5/38 (13.2%) 1/39 (2.6%) 4/38 (10.5%) 3/76 (3.9%) 1/40 (2.5%) 3/38 (7.9%)
Diarrhoea 14/38 (36.8%) 7/38 (18.4%) 15/38 (39.5%) 42/77 (54.5%) 16/38 (42.1%) 12/39 (30.8%) 14/38 (36.8%) 29/76 (38.2%) 14/40 (35%) 8/38 (21.1%)
Diverticulum 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Dry mouth 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Dyschezia 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 1/38 (2.6%)
Dyspepsia 3/38 (7.9%) 1/38 (2.6%) 1/38 (2.6%) 1/77 (1.3%) 10/38 (26.3%) 5/39 (12.8%) 4/38 (10.5%) 6/76 (7.9%) 3/40 (7.5%) 10/38 (26.3%)
Eosinophilic oesophagitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Eructation 1/38 (2.6%) 1/38 (2.6%) 2/38 (5.3%) 5/77 (6.5%) 5/38 (13.2%) 1/39 (2.6%) 3/38 (7.9%) 4/76 (5.3%) 2/40 (5%) 2/38 (5.3%)
Faeces hard 2/38 (5.3%) 2/38 (5.3%) 2/38 (5.3%) 3/77 (3.9%) 5/38 (13.2%) 0/39 (0%) 2/38 (5.3%) 2/76 (2.6%) 1/40 (2.5%) 3/38 (7.9%)
Flatulence 7/38 (18.4%) 9/38 (23.7%) 9/38 (23.7%) 21/77 (27.3%) 12/38 (31.6%) 6/39 (15.4%) 11/38 (28.9%) 21/76 (27.6%) 6/40 (15%) 8/38 (21.1%)
Frequent bowel movements 2/38 (5.3%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Gastritis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Gastrointestinal motility disorder 2/38 (5.3%) 2/38 (5.3%) 4/38 (10.5%) 3/77 (3.9%) 7/38 (18.4%) 0/39 (0%) 3/38 (7.9%) 2/76 (2.6%) 0/40 (0%) 4/38 (10.5%)
Gastrointestinal pain 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Gastrointestinal sounds abnormal 1/38 (2.6%) 1/38 (2.6%) 4/38 (10.5%) 5/77 (6.5%) 4/38 (10.5%) 1/39 (2.6%) 4/38 (10.5%) 3/76 (3.9%) 1/40 (2.5%) 3/38 (7.9%)
Gastrooesophageal reflux disease 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 3/77 (3.9%) 2/38 (5.3%) 3/39 (7.7%) 1/38 (2.6%) 4/76 (5.3%) 1/40 (2.5%) 3/38 (7.9%)
Glossodynia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Haematochezia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Haemorrhoidal haemorrhage 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Haemorrhoids 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Irritable bowel syndrome 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Large intestine polyp 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 1/40 (2.5%) 0/38 (0%)
Melaena 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Nausea 1/38 (2.6%) 3/38 (7.9%) 3/38 (7.9%) 3/77 (3.9%) 8/38 (21.1%) 3/39 (7.7%) 3/38 (7.9%) 4/76 (5.3%) 5/40 (12.5%) 5/38 (13.2%)
Splenic artery aneurysm 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Tooth disorder 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Toothache 0/38 (0%) 0/38 (0%) 0/38 (0%) 2/77 (2.6%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 3/76 (3.9%) 0/40 (0%) 1/38 (2.6%)
Vomiting 3/38 (7.9%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 1/38 (2.6%) 2/39 (5.1%) 0/38 (0%) 0/76 (0%) 2/40 (5%) 1/38 (2.6%)
General disorders
Asthenia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Chest discomfort 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Chest pain 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Chills 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Fatigue 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 2/38 (5.3%)
Feeling cold 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hunger 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Influenza like illness 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Oedema peripheral 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Pain 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Peripheral swelling 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Pyrexia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Thirst 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hepatobiliary disorders
Biliary dyskinesia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Cholelithiasis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Hepatic steatosis 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 1/38 (2.6%)
Immune system disorders
Drug hypersensitivity 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Seasonal allergy 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Infections and infestations
Acute sinusitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Bacterial vulvovaginitis 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Balanitis candida 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Bronchitis 4/38 (10.5%) 0/38 (0%) 2/38 (5.3%) 2/77 (2.6%) 0/38 (0%) 2/39 (5.1%) 2/38 (5.3%) 2/76 (2.6%) 3/40 (7.5%) 2/38 (5.3%)
Cellulitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Cystitis 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Cystitis bacterial 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 1/40 (2.5%) 0/38 (0%)
Ear infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Epiglottitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Escherichia urinary tract infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Eye infection 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Folliculitis 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 1/38 (2.6%)
Fungal infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Fungal skin infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Gastroenteritis 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 2/40 (5%) 1/38 (2.6%)
Gastroenteritis viral 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 2/77 (2.6%) 0/38 (0%) 2/39 (5.1%) 1/38 (2.6%) 1/76 (1.3%) 1/40 (2.5%) 1/38 (2.6%)
Gastrointestinal viral infection 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Genital candidiasis 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Genital herpes zoster 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Genital infection fungal 0/38 (0%) 0/38 (0%) 0/38 (0%) 2/77 (2.6%) 1/38 (2.6%) 2/39 (5.1%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Helicobacter infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Herpes simplex 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Hordeolum 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Influenza 2/38 (5.3%) 0/38 (0%) 0/38 (0%) 3/77 (3.9%) 5/38 (13.2%) 2/39 (5.1%) 2/38 (5.3%) 3/76 (3.9%) 1/40 (2.5%) 2/38 (5.3%)
Nasopharyngitis 4/38 (10.5%) 2/38 (5.3%) 3/38 (7.9%) 8/77 (10.4%) 4/38 (10.5%) 3/39 (7.7%) 7/38 (18.4%) 5/76 (6.6%) 0/40 (0%) 2/38 (5.3%)
Onychomycosis 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Oral candidiasis 0/38 (0%) 2/38 (5.3%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Oral herpes 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Otitis externa 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Otitis externa fungal 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Otitis media 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Paronychia 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Pharyngitis 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Pharyngitis streptococcal 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Pneumonia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Post procedural infection 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Pulpitis dental 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Rhinitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 3/77 (3.9%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 1/40 (2.5%) 0/38 (0%)
Sinobronchitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Sinusitis 1/38 (2.6%) 1/38 (2.6%) 3/38 (7.9%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 1/38 (2.6%) 3/76 (3.9%) 3/40 (7.5%) 0/38 (0%)
Tinea pedis 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Tonsillitis 1/38 (2.6%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Tooth abscess 2/38 (5.3%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Tooth infection 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Tracheitis 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Upper respiratory tract infection 2/38 (5.3%) 3/38 (7.9%) 3/38 (7.9%) 7/77 (9.1%) 2/38 (5.3%) 2/39 (5.1%) 1/38 (2.6%) 2/76 (2.6%) 5/40 (12.5%) 5/38 (13.2%)
Urinary tract infection 3/38 (7.9%) 1/38 (2.6%) 3/38 (7.9%) 1/77 (1.3%) 1/38 (2.6%) 4/39 (10.3%) 4/38 (10.5%) 4/76 (5.3%) 2/40 (5%) 5/38 (13.2%)
Urinary tract infection bacterial 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vaginal infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 2/77 (2.6%) 0/38 (0%) 2/39 (5.1%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Vestibular neuronitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Viral infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 2/39 (5.1%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 3/38 (7.9%)
Viral upper respiratory tract infection 2/38 (5.3%) 1/38 (2.6%) 0/38 (0%) 2/77 (2.6%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Vulvitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 2/76 (2.6%) 0/40 (0%) 0/38 (0%)
Vulvovaginal candidiasis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vulvovaginal mycotic infection 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 3/76 (3.9%) 1/40 (2.5%) 0/38 (0%)
Wound infection 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Anastomotic ulcer 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Animal bite 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Ankle fracture 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Contusion 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Epicondylitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Fall 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Foot fracture 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Hand fracture 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Joint injury 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Laceration 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Ligament rupture 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Ligament sprain 1/38 (2.6%) 0/38 (0%) 3/38 (7.9%) 4/77 (5.2%) 2/38 (5.3%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 1/40 (2.5%) 1/38 (2.6%)
Limb injury 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Muscle rupture 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Muscle strain 0/38 (0%) 2/38 (5.3%) 1/38 (2.6%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Post procedural complication 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Post procedural discomfort 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Post-traumatic pain 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Procedural pain 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Skin abrasion 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Tooth fracture 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Investigations
Amylase decreased 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Apolipoprotein A-I decreased 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Blood albumin increased 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Blood alkaline phosphatase increased 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Blood creatinine increased 2/38 (5.3%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 1/39 (2.6%) 1/38 (2.6%) 3/76 (3.9%) 0/40 (0%) 0/38 (0%)
Blood glucose increased 2/38 (5.3%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Blood magnesium decreased 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Blood potassium decreased 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Blood potassium increased 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Blood uric acid increased 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Cardiac murmur 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Creatinine urine increased 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Electrocardiogram change 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Gamma-glutamyltransferase increased 2/38 (5.3%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Glomerular filtration rate decreased 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Glomerular filtration rate increased 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Glycosylated haemoglobin increased 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Haematocrit increased 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Haemoglobin increased 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Haemoglobin urine present 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Heart rate decreased 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Heart rate irregular 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
High density lipoprotein decreased 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Lipase abnormal 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Lipase increased 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Liver function test increased 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Liver scan abnormal 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Prostatic specific antigen increased 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Protein urine present 1/38 (2.6%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Serum ferritin decreased 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Urine albumin/creatinine ratio increased 2/38 (5.3%) 1/38 (2.6%) 3/38 (7.9%) 1/77 (1.3%) 5/38 (13.2%) 1/39 (2.6%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Urine leukocyte esterase 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Urine leukocyte esterase positive 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 1/38 (2.6%)
Weight increased 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Metabolism and nutrition disorders
Appetite disorder 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Decreased appetite 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Dehydration 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Diabetes mellitus 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Gout 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 2/38 (5.3%)
Hypercholesterolaemia 0/38 (0%) 1/38 (2.6%) 1/38 (2.6%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hyperglycaemia 1/38 (2.6%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 2/76 (2.6%) 0/40 (0%) 0/38 (0%)
Hyperkalaemia 0/38 (0%) 0/38 (0%) 2/38 (5.3%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hyperlipidaemia 0/38 (0%) 2/38 (5.3%) 0/38 (0%) 2/77 (2.6%) 1/38 (2.6%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Hypoglycaemia 1/38 (2.6%) 1/38 (2.6%) 0/38 (0%) 3/77 (3.9%) 4/38 (10.5%) 2/39 (5.1%) 1/38 (2.6%) 1/76 (1.3%) 1/40 (2.5%) 2/38 (5.3%)
Hypokalaemia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Hypomagnesaemia 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Increased appetite 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Iron deficiency 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Ketosis 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Polydipsia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Type 2 diabetes mellitus 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vitamin D deficiency 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Musculoskeletal and connective tissue disorders
Arthralgia 2/38 (5.3%) 1/38 (2.6%) 0/38 (0%) 6/77 (7.8%) 2/38 (5.3%) 2/39 (5.1%) 2/38 (5.3%) 2/76 (2.6%) 2/40 (5%) 2/38 (5.3%)
Arthritis 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Back pain 3/38 (7.9%) 4/38 (10.5%) 1/38 (2.6%) 7/77 (9.1%) 2/38 (5.3%) 4/39 (10.3%) 3/38 (7.9%) 5/76 (6.6%) 3/40 (7.5%) 1/38 (2.6%)
Bursitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Costochondritis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Dupuytren's contracture 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Exostosis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 1/38 (2.6%)
Extremity contracture 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Fibromyalgia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Flank pain 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Intervertebral disc protrusion 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Joint effusion 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Joint swelling 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 1/38 (2.6%)
Muscle spasms 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 2/40 (5%) 1/38 (2.6%)
Musculoskeletal chest pain 0/38 (0%) 1/38 (2.6%) 1/38 (2.6%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Musculoskeletal pain 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 2/38 (5.3%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 2/40 (5%) 0/38 (0%)
Myalgia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Neck pain 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Osteoarthritis 2/38 (5.3%) 2/38 (5.3%) 0/38 (0%) 3/77 (3.9%) 1/38 (2.6%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 1/38 (2.6%)
Pain in extremity 3/38 (7.9%) 3/38 (7.9%) 1/38 (2.6%) 2/77 (2.6%) 0/38 (0%) 2/39 (5.1%) 1/38 (2.6%) 3/76 (3.9%) 0/40 (0%) 1/38 (2.6%)
Pain in jaw 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Plantar fasciitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Scleroderma 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Spinal osteoarthritis 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Spinal pain 0/38 (0%) 0/38 (0%) 2/38 (5.3%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Tendon pain 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Tendonitis 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Tenosynovitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Trigger finger 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Benign neoplasm of conjunctiva 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Neuroma 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Papilloma 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Nervous system disorders
Carpal tunnel syndrome 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 1/38 (2.6%)
Dizziness 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 2/39 (5.1%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Dizziness postural 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Facial paralysis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Headache 2/38 (5.3%) 1/38 (2.6%) 0/38 (0%) 2/77 (2.6%) 0/38 (0%) 3/39 (7.7%) 1/38 (2.6%) 1/76 (1.3%) 1/40 (2.5%) 1/38 (2.6%)
Hypoaesthesia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hyposmia 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Migraine 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 2/77 (2.6%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Nerve compression 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Paraesthesia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Sciatica 1/38 (2.6%) 2/38 (5.3%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Sinus headache 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Syncope 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Tremor 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Product Issues
Device dislocation 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Psychiatric disorders
Anxiety 1/38 (2.6%) 0/38 (0%) 2/38 (5.3%) 3/77 (3.9%) 1/38 (2.6%) 1/39 (2.6%) 1/38 (2.6%) 1/76 (1.3%) 2/40 (5%) 2/38 (5.3%)
Binge drinking 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Depression 1/38 (2.6%) 2/38 (5.3%) 1/38 (2.6%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 2/38 (5.3%) 1/76 (1.3%) 0/40 (0%) 2/38 (5.3%)
Grief reaction 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Insomnia 1/38 (2.6%) 1/38 (2.6%) 2/38 (5.3%) 2/77 (2.6%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 1/40 (2.5%) 0/38 (0%)
Organic brain syndrome 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Schizophrenia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Stress 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Renal and urinary disorders
Acute kidney injury 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Dysuria 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 0/40 (0%) 1/38 (2.6%)
Haematuria 0/38 (0%) 0/38 (0%) 0/38 (0%) 2/77 (2.6%) 1/38 (2.6%) 2/39 (5.1%) 2/38 (5.3%) 0/76 (0%) 3/40 (7.5%) 1/38 (2.6%)
Hypertonic bladder 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Lower urinary tract symptoms 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Microalbuminuria 0/38 (0%) 1/38 (2.6%) 2/38 (5.3%) 1/77 (1.3%) 3/38 (7.9%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 3/38 (7.9%)
Pollakiuria 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 2/38 (5.3%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Proteinuria 1/38 (2.6%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 1/38 (2.6%) 2/39 (5.1%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 3/38 (7.9%)
Renal cyst 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 2/76 (2.6%) 0/40 (0%) 0/38 (0%)
Renal impairment 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Urinary incontinence 1/38 (2.6%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Reproductive system and breast disorders
Atrophic vulvovaginitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Balanoposthitis 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Breast haematoma 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Endometrial hyperplasia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Epididymal cyst 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Menopausal symptoms 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Menorrhagia 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Menstrual disorder 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Metrorrhagia 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Prostatomegaly 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Scrotal oedema 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vaginal discharge 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vulval disorder 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vulvovaginal pruritus 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 2/38 (5.3%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 4/77 (5.2%) 0/38 (0%) 1/39 (2.6%) 1/38 (2.6%) 2/76 (2.6%) 0/40 (0%) 3/38 (7.9%)
Dysphonia 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Dyspnoea 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Epistaxis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Hydrothorax 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Nasal congestion 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 2/38 (5.3%)
Oropharyngeal pain 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 1/77 (1.3%) 0/38 (0%) 1/39 (2.6%) 2/38 (5.3%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Pleuritic pain 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Respiratory tract congestion 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Rhinitis allergic 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Sinus congestion 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 1/76 (1.3%) 1/40 (2.5%) 0/38 (0%)
Sleep apnoea syndrome 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Sneezing 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Upper respiratory tract congestion 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Upper-airway cough syndrome 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Skin and subcutaneous tissue disorders
Dermal cyst 0/38 (0%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Dermatitis allergic 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Dermatitis contact 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Eczema 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Hyperkeratosis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Lichen sclerosus 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Pruritus 0/38 (0%) 2/38 (5.3%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Pustular psoriasis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (0%)
Rash 0/38 (0%) 0/38 (0%) 0/38 (0%) 1/77 (1.3%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 2/76 (2.6%) 0/40 (0%) 0/38 (0%)
Rash maculo-papular 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Rosacea 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Skin fissures 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Skin ulcer 0/38 (0%) 0/38 (0%) 1/38 (2.6%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Urticaria 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Vascular disorders
Hot flush 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 1/38 (2.6%) 1/76 (1.3%) 0/40 (0%) 0/38 (0%)
Hypertension 1/38 (2.6%) 1/38 (2.6%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 1/39 (2.6%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 3/38 (7.9%)
Hypotension 1/38 (2.6%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 2/39 (5.1%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Peripheral arterial occlusive disease 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Peripheral venous disease 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 1/38 (2.6%)
Shock haemorrhagic 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 1/38 (2.6%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 0/40 (0%) 0/38 (0%)
Thrombophlebitis 0/38 (0%) 0/38 (0%) 0/38 (0%) 0/77 (0%) 0/38 (0%) 0/39 (0%) 0/38 (0%) 0/76 (0%) 1/40 (2.5%) 0/38 (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 (ie, data from all sites) in the clinical trial.

Results Point of Contact

Name/Title Study Director
Organization Novartis Pharmaceuticals
Phone 862-778-8300
Email Novartis.email@novartis.com
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03100058
Other Study ID Numbers:
  • CLIK066B2201
  • 2016-002868-14
First Posted:
Apr 4, 2017
Last Update Posted:
Feb 6, 2020
Last Verified:
Jan 1, 2020