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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: Placebo; Drug: LIK066

• Study Type: Interventional
• Enrollment (Actual): 460
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Novartis Investigative Site
  • Wien, Austria, 1010
    • Novartis Investigative Site
  • Wien, Austria, 1030
    • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M9W 4L6
      • Novartis Investigative Site
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 6S8
      • Novartis Investigative Site
    • Levis, Quebec, Canada, G6W 5M6
      • Novartis Investigative Site
• Czechia
  • Ceske Budejovice, Czechia, 370 01
    • Novartis Investigative Site
  • Olomouc Lazce, Czechia, 77900
    • Novartis Investigative Site
  • Praha 1, Czechia, 116 94
    • Novartis Investigative Site
  • Praha 3, Czechia, 13000
    • Novartis Investigative Site
  • Slany, Czechia, 274 01
    • Novartis Investigative Site
  • Czech Republic
    • Praha 2, Czech Republic, Czechia, 128 08
      • Novartis Investigative Site
• Hungary
  • Csongrad, Hungary, 6640
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary, 4400
    • Novartis Investigative Site
  • Szentes, Hungary, 6600
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 85101
    • Novartis Investigative Site
  • Kosice, Slovakia, 040 01
    • Novartis Investigative Site
  • Sered, Slovakia, 92601
    • Novartis Investigative Site
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9DT
    • Novartis Investigative Site
  • Blackburn, United Kingdom, BB2 1AX
    • Novartis Investigative Site
  • Exeter, United Kingdom, EX2 5DW
    • Novartis Investigative Site
  • Rotherham, United Kingdom, S65 1DA
    • Novartis Investigative Site
  • Stevenage, United Kingdom, SG1 4AB
    • Novartis Investigative Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Novartis Investigative Site
    • Jasper, Alabama, United States, 35501
      • Novartis Investigative Site
  • California
    • Beverly Hills, California, United States, 90211
      • Novartis Investigative Site
    • Carmichael, California, United States, 95608
      • Novartis Investigative Site
    • Concord, California, United States, 94520
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90017
      • Novartis Investigative Site
    • Northridge, California, United States, 91325
      • Novartis Investigative Site
    • Roseville, California, United States, 95661
      • Novartis Investigative Site
    • San Ramon, California, United States, 94582
      • Novartis Investigative Site
    • Stockton, California, United States, 95204
      • Novartis Investigative Site
    • Walnut Creek, California, United States, 94598
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80246
      • Novartis Investigative Site
    • Golden, Colorado, United States, 80401
      • Novartis Investigative Site
  • Florida
    • Bradenton, Florida, United States, 34209
      • Novartis Investigative Site
    • Fort Lauderdale, Florida, United States, 33312
      • Novartis Investigative Site
    • Port Charlotte, Florida, United States, 33952
      • Novartis Investigative Site
    • West Palm Beach, Florida, United States, 33401
      • Novartis Investigative Site
  • Georgia
    • Athens, Georgia, United States, 30606
      • Novartis Investigative Site
    • Augusta, Georgia, United States, 30909
      • Novartis Investigative Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novartis Investigative Site
  • Illinois
    • Gurnee, Illinois, United States, 60031
      • Novartis Investigative Site
    • Springfield, Illinois, United States, 62711
      • Novartis Investigative Site
    • Wauconda, Illinois, United States, 60084
      • Novartis Investigative Site
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Novartis Investigative Site
    • Evansville, Indiana, United States, 47714
      • Novartis Investigative Site
    • Indianapolis, Indiana, United States, 46260
      • Novartis Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Novartis Investigative Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Novartis Investigative Site
    • Covington, Louisiana, United States, 70433
      • Novartis Investigative Site
    • Hammond, Louisiana, United States, 70403
      • Novartis Investigative Site
    • Metairie, Louisiana, United States, 70006
      • Novartis Investigative Site
    • New Orleans, Louisiana, United States, 70115
      • Novartis Investigative Site
    • New Orleans, Louisiana, United States, 70119
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Novartis Investigative Site
    • Beltsville, Maryland, United States, 20705
      • Novartis Investigative Site
    • Towson, Maryland, United States, 21204
      • Novartis Investigative Site
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Novartis Investigative Site
    • Saint Peters, Missouri, United States, 63303
      • Novartis Investigative Site
  • Montana
    • Missoula, Montana, United States, 59808
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Novartis Investigative Site
  • New York
    • Bronx, New York, United States, 10455
      • Novartis Investigative Site
    • New York, New York, United States, 10016
      • Novartis Investigative Site
    • New York, New York, United States, 10021
      • Novartis Investigative Site
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Novartis Investigative Site
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446
      • Novartis Investigative Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Novartis Investigative Site
  • South Carolina
    • Moncks Corner, South Carolina, United States, 29464
      • Novartis Investigative Site
    • Mount Pleasant, South Carolina, United States, 29464
      • Novartis Investigative Site
    • Summerville, South Carolina, United States, 29485
      • Novartis Investigative Site
  • Texas
    • Houston, Texas, United States, 77081
      • Novartis Investigative Site
  • Utah
    • Bountiful, Utah, United States, 84010
      • Novartis Investigative Site
    • Salt Lake City, Utah, United States, 84102
      • Novartis Investigative Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Novartis Investigative Site
    • Richmond, Virginia, United States, 23294
      • Novartis Investigative Site
    • Richmond, Virginia, United States, 23235
      • Novartis Investigative Site
  • Washington
    • Renton, Washington, United States, 98057
      • Novartis Investigative Site
    • Tacoma, Washington, United States, 98405
      • Novartis Investigative Site
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

13

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Body Weight at 24 Weeks	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	Baseline, Week 24 (Epoch 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study	Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline	Baseline, Week 24
Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups	Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline for dysglycemic, normoglycemic, Type 2 Diabetes Mellitus (T2DM)	Baseline, Week 24
Percentage Change From Baseline on Waist Circumference	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.	Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)
Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM)	FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake).	Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM)	HbA1c will be measured from a blood sample obtained at indicated visits and will be analyzed at a central laboratory.	Baseline, Week 24 (Epoch 3), Week 24 to week 48 (Epoch 4)
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP)	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	Baseline, Week 24 (Epoch 3) Week 24 to Week 48 (Epoch 4)
Change From Baseline in 24-hour Urinary Glucose Excretion	Urinary glucose excretion will be measured from 24-hour urinary collection at indicated visits and will be analyzed at a central laboratory.	Baseline, week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)
Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4)	Between -treatment analysis of percentage change from Week 24 in body weight (kg) at Week 48 (Epoch 4)	Between Week 24 and Week 48 (Epoch 4)
Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion	Evaluation of 24-hour urinary calcium excretion after 24 week of treatment.	Baseline, Week 24
Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion	Evaluation of 24-hour urinary calcium after 48 weeks of treatment	Baseline, Week 24, Week 48
Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion	Evaluation of 24-hour urinary phosphorus excretion after 24 weeks of treatment	Week 24, Week 48
Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion	Evaluation of 24-hour urinary phosphorus excretion after 48 weeks of treatment	Week 24, Week 48
Change From Baseline in Fasting Lipid Profile (Lipoproteins)	Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48	Baseline, Week 24, Week 24 to Week 48 (Epoch 4)
Change From Baseline in High Sensitive C-reactive Protein (hsCRP)	Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48	Baseline to Week 24, Week 24 to Week 48 (Epoch 4)
Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol)	Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48	Baseline to Week 24, Week 24 to Week 48 (Epoch 4)
Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax)	Observe maximum plasma concentration following administration of LIK066 (Cmax)	Summary at Week 24 from qd or bid regimens
Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax)	Time to reach the maximum concentration after administration of LIK066 (Tmax)	Summary at Week 24 for qd or bid regimens
Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t)	Area under the plasma concentration-time curve from time zero time 't' where t is a defined time point after administration (AUC0-t)	Summary at Week 24 from qd or bid regimens (0-6h)
Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast)	Last non-zero concentration area under the curve (AUClast)	Summary at Week 24 from qd or bid regimens

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 6, 2017
• Primary Completion (ACTUAL): March 2, 2018
• Study Completion (ACTUAL): August 2, 2018

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: March 28, 2017
• First Posted (ACTUAL): April 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Obesity; Overweight
• Additional Relevant MeSH Terms: Body Weight; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Licogliflozin
• Other Study ID Numbers: CLIK066B2201; 2016-002868-14 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No