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NCT03320941

A Dose-finding Study to Evaluate the Change in Weight After Treatment With LIK066 in Japanese Patients With Obesity

Completed Phase 2 Results posted Last updated 26 June 2024
What this trial tests

Phase 2 trial testing LIK066 in Obesity in 126 participants. Completed in 25 July 2018.

Timeline
7 December 2017
Primary endpoint
25 July 2018
25 July 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment126
Start date7 December 2017
Primary completion25 July 2018
Estimated completion25 July 2018
Sites24 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 20 to 75, any sex, with Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage Change From Baseline in Body Weight at Week 12 Primary · Baseline, Week 12

The dose-response relationship of LIK066 as measured by percent change from baseline in body weight relative to placebo after 12 weeks of treatment.

GroupValue95% CI
LIK066 2.5mg qd-1.86-2.59 – -0.67
LIK066 10mg qd-2.84-3.79 – -2.16
LIK066 25 mg qd-3.41-3.96 – -2.84
LIK066 50 mg qd-3.80-4.48 – -3.17
Placebo0.11-0.90 – 0.97
Responder Rates According to Percentage Decrease in Body Weight From Baseline to Week 12 Secondary · Baseline, Week 12

The responder rates according to percentage decrease in body weight either ≥ 3%, ≥ 5% or ≥ 10%, from baseline at Week 12, for the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12 No Statistical Analysis for \>=5% and \>=10% was not calculated due to division by zero

>= 3%
GroupValue95% CI
LIK066 2.5mg qd15.8
LIK066 10mg qd55.6
LIK066 25 mg qd50.0
LIK066 50 mg qd56.7
Placebo7.1
>= 5%
GroupValue95% CI
LIK066 2.5mg qd5.3
LIK066 10mg qd27.8
LIK066 25 mg qd17.9
LIK066 50 mg qd26.7
Placebo0.0
>= 10%
GroupValue95% CI
LIK066 2.5mg qd0.0
LIK066 10mg qd0.0
LIK066 25 mg qd0.0
LIK066 50 mg qd3.3
Placebo0.0
>= 3% (Dysglycemic)
GroupValue95% CI
LIK066 2.5mg qd12.5
LIK066 10mg qd75.0
LIK066 25 mg qd38.5
LIK066 50 mg qd46.2
Placebo7.7
>= 5% (Dysglycemic)
GroupValue95% CI
LIK066 2.5mg qd0.0
LIK066 10mg qd62.5
LIK066 25 mg qd23.1
LIK066 50 mg qd23.1
Placebo0.0
>= 10% (Dysglycemic)
GroupValue95% CI
LIK066 2.5mg qd0.0
LIK066 10mg qd0.0
LIK066 25 mg qd0.0
LIK066 50 mg qd0.0
Placebo0.0
>= 3% (T2DM)
GroupValue95% CI
LIK066 2.5mg qd18.2
LIK066 10mg qd40.0
LIK066 25 mg qd60.0
LIK066 50 mg qd64.7
Placebo6.7
>= 5% (T2DM)
GroupValue95% CI
LIK066 2.5mg qd9.1
LIK066 10mg qd0.00
LIK066 25 mg qd13.3
LIK066 50 mg qd29.4
Placebo0.00
Percentage Change From Baseline in Body Weight at Week 12 in Dysglycemic Participants and Participants With Type 2 Diabetes Mellitus (T2DM) Secondary · Baseline, Week 12

The dose-response relationship for weight loss in dysglycemic participants and participants with T2DM. Percentage change from baseline in body weight at Week 12.

Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-1.90-3.17 – -0.37
LIK066 10mg qd-2.95-3.95 – -2.15
LIK066 25 mg qd-3.29-4.19 – -2.57
LIK066 50 mg qd-3.47-4.31 – -2.54
Placebo0.00-1.25 – 1.19
T2DM
GroupValue95% CI
LIK066 2.5mg qd-1.64-2.54 – -0.26
LIK066 10mg qd-2.66-3.49 – -1.16
LIK066 25 mg qd-3.42-4.30 – -2.42
LIK066 50 mg qd-4.23-5.63 – -3.27
Placebo0.10-1.40 – 1.48
Change From Baseline at Week 12 on Waist Circumference at Umbilical Level Secondary · Baseline, Week 12

Waist circumference will be measured to the nearest 0.1 cm in a standing position, at the end of a normal expiration, using a tape at the level of umbilicus. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd-2.47-4.003 – -0.937
LIK066 10mg qd-2.63-4.172 – -1.082
LIK066 25 mg qd-2.65-3.907 – -1.393
LIK066 50 mg qd-3.11-4.320 – -1.895
Placebo-1.37-2.636 – -0.100
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-2.78-5.187 – -0.368
LIK066 10mg qd-4.49-6.856 – -2.123
LIK066 25 mg qd-2.08-3.977 – -0.177
LIK066 50 mg qd-2.23-4.123 – -0.333
Placebo-0.41-2.312 – 1.483
T2DM
GroupValue95% CI
LIK066 2.5mg qd-2.22-4.156 – -0.283
LIK066 10mg qd-1.39-3.418 – 0.631
LIK066 25 mg qd-2.90-4.557 – -1.244
LIK066 50 mg qd-3.88-5.416 – -2.340
Placebo-2.19-3.859 – -0.520
Percentage Change From Baseline at Week 12 on Hemoglobin A1c (HbA1c) Secondary · Baseline, Week 12

HbA1c will be measured from a blood sample obtained and analyzed at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd-0.285-0.415 – -0.155
LIK066 10mg qd-0.355-0.488 – -0.223
LIK066 25 mg qd-0.366-0.473 – -0.259
LIK066 50 mg qd-0.418-0.521 – -0.314
Placebo-0.079-0.187 – 0.028
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-0.139-0.261 – -0.016
LIK066 10mg qd-0.184-0.306 – -0.062
LIK066 25 mg qd-0.196-0.292 – -0.101
LIK066 50 mg qd-0.163-0.259 – -0.067
Placebo-0.050-0.146 – 0.046
T2DM
GroupValue95% CI
LIK066 2.5mg qd-0.405-0.616 – -0.195
LIK066 10mg qd-0.491-0.708 – -0.275
LIK066 25 mg qd-0.502-0.679 – -0.325
LIK066 50 mg qd-0.618-0.784 – -0.452
Placebo-0.093-0.271 – 0.086
Change From Baseline at Week 12 on Fasting Plasma Glucose (FPG) Secondary · Baseline, Week 12

FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake) at a central laboratory. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd-0.334-0.652 – -0.016
LIK066 10mg qd-0.665-0.990 – -0.340
LIK066 25 mg qd-0.747-1.007 – -0.486
LIK066 50 mg qd-0.986-1.238 – -0.733
Placebo-0.160-0.423 – 0.103
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd0.002-0.322 – 0.326
LIK066 10mg qd-0.126-0.453 – 0.200
LIK066 25 mg qd-0.262-0.515 – -0.008
LIK066 50 mg qd-0.472-0.728 – -0.217
Placebo-0.217-0.471 – 0.038
T2DM
GroupValue95% CI
LIK066 2.5mg qd-0.606-1.095 – -0.118
LIK066 10mg qd-1.111-1.619 – -0.604
LIK066 25 mg qd-1.145-1.559 – -0.730
LIK066 50 mg qd-1.377-1.766 – -0.988
Placebo-0.079-0.497 – 0.339
Change From Baseline at Week 12 on Systolic Blood Pressure (SBP) Secondary · Baseline, Week 12

After the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP will be measured three times using the automatic BP monitor and an appropriate size cuff. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd-4.90-9.049 – -0.746
LIK066 10mg qd-5.12-9.403 – -0.834
LIK066 25 mg qd-6.36-9.781 – -2.935
LIK066 50 mg qd-6.94-10.233 – -3.655
Placebo-5.36-8.758 – -1.961
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-5.79-12.457 – 0.883
LIK066 10mg qd-7.10-13.825 – -0.369
LIK066 25 mg qd-3.58-8.811 – 1.657
LIK066 50 mg qd-4.17-9.399 – 1.051
Placebo-7.09-12.294 – -1.891
T2DM
GroupValue95% CI
LIK066 2.5mg qd-4.16-9.414 – 1.091
LIK066 10mg qd-2.96-8.500 – 2.588
LIK066 25 mg qd-8.63-13.143 – -4.120
LIK066 50 mg qd-9.00-13.182 – -4.810
Placebo-3.77-8.255 – 0.724
Change From Baseline at Week 12 on Diastolic Blood Pressure (DBP) Secondary · Baseline, Week 12

After the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, DBP will be measured three times using the automatic BP monitor and an appropriate size cuff. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd-3.72-6.803 – -0.627
LIK066 10mg qd-3.54-6.700 – -0.377
LIK066 25 mg qd-4.36-6.892 – -1.818
LIK066 50 mg qd-5.23-7.677 – -2.788
Placebo-3.12-5.647 – -0.597
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-3.32-8.404 – 1.769
LIK066 10mg qd-4.40-9.490 – 0.699
LIK066 25 mg qd-2.46-6.441 – 1.513
LIK066 50 mg qd-4.25-8.230 – -0.279
Placebo-4.31-8.257 – -0.357
T2DM
GroupValue95% CI
LIK066 2.5mg qd-4.00-7.943 – -0.059
LIK066 10mg qd-2.45-6.584 – 1.687
LIK066 25 mg qd-5.98-9.352 – -2.607
LIK066 50 mg qd-5.92-9.066 – -2.776
Placebo-1.93-5.303 – 1.448
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Triglycerides (TG) Secondary · Baseline, Week 12

Fasting lipid profile (Triglycerides (TG)), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd1.840-30.956 – 34.636
LIK066 10mg qd11.057-22.372 – 44.487
LIK066 25 mg qd43.92817.118 – 70.737
LIK066 50 mg qd5.307-20.648 – 31.261
Placebo17.401-9.474 – 44.275
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-1.153-62.637 – 60.331
LIK066 10mg qd-1.986-64.104 – 60.132
LIK066 25 mg qd52.2843.839 – 100.729
LIK066 50 mg qd14.061-34.625 – 62.746
Placebo20.962-27.416 – 69.340
T2DM
GroupValue95% CI
LIK066 2.5mg qd1.016-36.069 – 38.100
LIK066 10mg qd23.108-14.937 – 61.153
LIK066 25 mg qd34.7473.600 – 65.893
LIK066 50 mg qd-0.057-29.478 – 29.363
Placebo13.806-17.085 – 44.697
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Total Cholesterol Secondary · Baseline, Week 12

Fasting lipid profile (total cholesterol), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd-1.290-6.809 – 4.229
LIK066 10mg qd-2.983-8.711 – 2.745
LIK066 25 mg qd0.884-3.663 – 5.430
LIK066 50 mg qd0.302-4.096 – 4.700
Placebo-2.244-6.800 – 2.312
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-3.055-12.284 – 6.173
LIK066 10mg qd-6.017-15.916 – 3.882
LIK066 25 mg qd4.273-3.085 – 11.630
LIK066 50 mg qd-1.734-9.000 – 5.532
Placebo-3.559-10.940 – 3.822
T2DM
GroupValue95% CI
LIK066 2.5mg qd0.158-6.814 – 7.129
LIK066 10mg qd-1.367-8.670 – 5.937
LIK066 25 mg qd-1.646-7.772 – 4.481
LIK066 50 mg qd1.817-3.857 – 7.491
Placebo-0.671-6.635 – 5.294
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - High Density Lipoprotein (HDL) Secondary · Baseline, Week 12

Fasting lipid profile (HDL), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd1.499-3.683 – 6.682
LIK066 10mg qd-2.461-7.790 – 2.868
LIK066 25 mg qd-5.253-9.514 – -0.993
LIK066 50 mg qd0.112-4.014 – 4.237
Placebo-3.454-7.739 – 0.830
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-0.519-9.144 – 8.107
LIK066 10mg qd0.329-8.368 – 9.027
LIK066 25 mg qd-3.279-10.056 – 3.498
LIK066 50 mg qd-0.147-6.917 – 6.622
Placebo-4.329-11.096 – 2.437
T2DM
GroupValue95% CI
LIK066 2.5mg qd2.886-3.774 – 9.545
LIK066 10mg qd-4.696-11.654 – 2.261
LIK066 25 mg qd-6.993-12.672 – -1.315
LIK066 50 mg qd0.235-5.133 – 5.604
Placebo-2.677-8.484 – 3.130
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Low Density Lipoprotein (LDL) Secondary · Baseline, Week 12

Fasting lipid profile (LDL), will be measured on blood samples obtained after an overnight fast and analyzed at a central laboratory For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12

Overall Study
GroupValue95% CI
LIK066 2.5mg qd0.757-7.220 – 8.734
LIK066 10mg qd-2.363-10.702 – 5.975
LIK066 25 mg qd0.037-6.524 – 6.598
LIK066 50 mg qd4.726-1.616 – 11.068
Placebo-0.552-7.154 – 6.051
Dysglycemic
GroupValue95% CI
LIK066 2.5mg qd-3.065-16.507 – 10.376
LIK066 10mg qd-4.473-18.904 – 9.958
LIK066 25 mg qd2.579-8.102 – 13.259
LIK066 50 mg qd2.128-8.426 – 12.681
Placebo-3.994-14.722 – 6.735
T2DM
GroupValue95% CI
LIK066 2.5mg qd3.727-6.379 – 13.833
LIK066 10mg qd-1.562-12.127 – 9.004
LIK066 25 mg qd-1.295-10.099 – 7.510
LIK066 50 mg qd6.803-1.311 – 14.917
Placebo2.942-5.699 – 11.584

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were collected till the end of the study.(about 12 weeks) and serious adverse events (SAEs) were collected until 30 days after the last study visit (12 weeks + 30 days = about 114 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LIK066 2.5mg qd
Serious: 0/19 (0%)
Deaths: 0/19
LIK066 10mg qd
Serious: 0/19 (0%)
Deaths: 0/19
LIK066 25mg qd
Serious: 0/28 (0%)
Deaths: 0/28
LIK066 50mg qd
Serious: 1/31 (3%)
Deaths: 0/31
Placebo
Serious: 0/29 (0%)
Deaths: 0/29

Serious adverse events (1 terms)

ReactionSystemLIK066 2.5mg qdLIK066 10mg qdLIK066 25mg qdLIK066 50mg qdPlacebo
Cholecystitis acuteHepatobiliary disorders
Other adverse events (32 terms — click to expand)

ReactionSystemLIK066 2.5mg qdLIK066 10mg qdLIK066 25mg qdLIK066 50mg qdPlacebo
DiarrhoeaGastrointestinal disorders
NasopharyngitisInfections and infestations
FlatulenceGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Protein urine presentInvestigations
Urine albumin/creatinine ratio increasedInvestigations
HypoglycaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
VertigoEar and labyrinth disorders
Gastric polypsGastrointestinal disorders
Gastritis erosiveGastrointestinal disorders
Large intestine polypGastrointestinal disorders
NauseaGastrointestinal disorders
MalaiseGeneral disorders
Hepatic steatosisHepatobiliary disorders
Asymptomatic bacteriuriaInfections and infestations
BronchitisInfections and infestations
CellulitisInfections and infestations
ConjunctivitisInfections and infestations
GingivitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Post-traumatic neck syndromeInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
White blood cells urine positiveInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
PeriarthritisMusculoskeletal and connective tissue disorders
HaematuriaRenal and urinary disorders
PollakiuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
EczemaSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders

Most-reported serious reactions: Cholecystitis acute.

Data from ClinicalTrials.gov NCT03320941 adverse events section.

Sponsor's own description

The purpose of the study is to evaluate the efficacy, tolerability and safety of LIK066 to support dose selection for Phase 3 development in Japanese adults with obesity disease.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Signaling pathways in obesity: mechanisms and therapeutic interventions.
    Wen X, Zhang B, Wu B, Xiao H, et al · · 2022 · cited 245× · PMID 36031641 · DOI 10.1038/s41392-022-01149-x
  2. Comprehensive Review of Current and Upcoming Anti-Obesity Drugs.
    Son JW, Kim S. · · 2020 · cited 92× · PMID 33389955 · DOI 10.4093/dmj.2020.0258
  3. The Extraglycemic Effect of SGLT-2is on Mineral and Bone Metabolism and Bone Fracture.
    Dong B, Lv R, Wang J, Che L, et al · · 2022 · cited 23× · PMID 35872985 · DOI 10.3389/fendo.2022.918350
  4. Dose-dependent reduction in body weight with LIK066 (licogliflozin) treatment in Japanese patients with obesity.
    Yokote K, Sano M, Tsumiyama I, Keefe D. · · 2020 · cited 15× · PMID 32072763 · DOI 10.1111/dom.14006
  5. Focus on Glucagon-like Peptide-1 Target: Drugs Approved or Designed to Treat Obesity.
    Zhang J, Wei J, Lai W, Sun J, et al · · 2025 · cited 2× · PMID 40004115 · DOI 10.3390/ijms26041651

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