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

A Randomized, Double-blind, Dose-finding Study to Evaluate the Change in Weight After 12 Weeks Treatment With 4 Doses of LIK066 Compared to Placebo in Japanese Patients With Obesity Disease

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Matsudo city, Chiba, Japan, 271 0077
      • Novartis Investigative Site
  • Fukuoka
    • Chikushino-city, Fukuoka, Japan, 818-0036
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 810-0066
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 819-0006
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 807-0857
      • Novartis Investigative Site
  • Hyogo
    • Akashi, Hyogo, Japan, 674-0081
      • Novartis Investigative Site
    • Kakogawa-city, Hyogo, Japan, 675-0101
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama-city, Kanagawa, Japan, 231-0023
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-0863
      • Novartis Investigative Site
    • Kumamoto-city, Kumamoto, Japan, 860-8039
      • Novartis Investigative Site
  • Kyoto
    • Kyoto city, Kyoto, Japan, 600-8898
      • Novartis Investigative Site
    • Kyoto-city, Kyoto, Japan, 615-8125
      • Novartis Investigative Site
  • Nagasaki
    • Nagasaki city, Nagasaki, Japan, 850 0045
      • Novartis Investigative Site
  • Osaka
    • Higashiosaka-city, Osaka, Japan, 577-0802
      • Novartis Investigative Site
    • Higashiosaka-city, Osaka, Japan, 577-0803
      • Novartis Investigative Site
  • Saitama
    • Ageo-city, Saitama, Japan, 362-8588
      • Novartis Investigative Site
    • Kawaguchi-City, Saitama, Japan, 332 0021
      • Novartis Investigative Site
    • Tokorozawa, Saitama, Japan
      • Novartis Investigative Site
    • Tokorozawa-city, Saitama, Japan, 359-0042
      • Novartis Investigative Site
  • Tokyo
    • Hachioji-city, Tokyo, Japan, 192-0046
      • Novartis Investigative Site
    • Kiyose-city, Tokyo, Japan, 204-0021
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 108-0075
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 141-0032
      • Novartis Investigative Site
    • Toshima-ku, Tokyo, Japan, 171-0021
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with obesity disease and inadequately controlled body weight with diet and/or exercise
• BMI ≥ 25 kg/m^2 combined with at least two obesity-related comorbidities, or BMI ≥ 35 kg/m^2 at least one obesity-related comorbidity
• Patients with FPG ≥ 110 mg/dL and/or 5.6% ≤ HbA1c ≤ 10.0%, or T2DM with HbA1c ≤ 10.0%
• Waist circumference at umbilical level ≥ 85 cm for male, ≥ 90 cm for female
• Visceral fat area ≥ 100 cm^2
• Agreement to comply with the study-required life-style intervention and treatment during the full duration of the study

Exclusion Criteria:

• Pregnancy or lactating women
• Use of pharmacologically active weight-loss medications
• Bariatric surgery
• Ketoacidosis, lactic acidosis, hyperosmolar coma
• Symptomatic genital ingection or urinary tract infection in the 4 weeks prior to screening
• Gastro-intestinal (GI) disorders associated with chronic diarrhea
• Congestive heart failure, New York Heart Association (NYHA) class III or IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LIK066 2.5 mg; Eligible patients randomized to this arm will receive LIK066 2.5 mg orally daily for 12 weeks.	Drug: LIK066; LIK066 will be supplied in different doses as tablets to be taken orally daily.
Experimental: LIK066 10 mg; Eligible patients randomized to this arm will receive LIK066 10 mg orally daily for 12 weeks.	Drug: LIK066; LIK066 will be supplied in different doses as tablets to be taken orally daily.
Experimental: LIK066 25 mg; Eligible patients randomized to this arm will receive LIK066 25 mg orally daily for 12 weeks.	Drug: LIK066; LIK066 will be supplied in different doses as tablets to be taken orally daily.
Experimental: LIK066 50 mg; Eligible patients randomized to this arm will receive LIK066 50 mg orally daily for 12 weeks.	Drug: LIK066; LIK066 will be supplied in different doses as tablets to be taken orally daily.
Placebo Comparator: Placebo; Eligible patient randomized to this arm will receive LIK066 matching placebo orally daily for 12 weeks.	Drug: Placebo; Placebo will be supplied as tablets to be taken daily orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Body Weight at 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.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder Rates According to Percentage Decrease in Body Weight From Baseline to 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	Baseline, Week 12
Percentage Change From Baseline in Body Weight at Week 12 in Dysglycemic Participants and Participants With Type 2 Diabetes Mellitus (T2DM)	The dose-response relationship for weight loss in dysglycemic participants and participants with T2DM. Percentage change from baseline in body weight at Week 12.	Baseline, Week 12
Change From Baseline at Week 12 on Waist Circumference at Umbilical Level	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	Baseline, Week 12
Percentage Change From Baseline at Week 12 on Hemoglobin A1c (HbA1c)	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	Baseline, Week 12
Change From Baseline at Week 12 on Fasting Plasma Glucose (FPG)	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	Baseline, Week 12
Change From Baseline at Week 12 on Systolic Blood Pressure (SBP)	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	Baseline, Week 12
Change From Baseline at Week 12 on Diastolic Blood Pressure (DBP)	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	Baseline, Week 12
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Triglycerides (TG)	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	Baseline, Week 12
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Total Cholesterol	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	Baseline, Week 12
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - High Density Lipoprotein (HDL)	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	Baseline, Week 12
Percentage Change From Baseline at Week 12 on Fasting Lipid Profile - Low Density Lipoprotein (LDL)	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	Baseline, Week 12
Percent Change From Baseline at Week 12 on High Sensitive C-reactive Protein (hsCRP)	High sensitivity CRP will be measured from a blood sample 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	Baseline, Week 12
Change From Baseline in Uric Acid at Week 12	Uric acid will be measured from a blood sample 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	Baseline, Week 12
Change From Baseline on Urine Albumin at Week 12	Urine albumin will be measured from urine sample 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	Baseline, Week 12
Change From Baseline on Urine Albumin to Creatinine Ratio at Week 12	Urine albumin to creatinine ratio will be measured from urine sample 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	Baseline, Week 12
Percent Change From Baseline on Visceral Fat Area (VFA) at Week 12	VFA by CT scan will be measured at visits and evaluated centrally. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12	Baseline, Week 12
Percent Change From Baseline on Subcutaneous Fat Area (SFA) at Week 12	SFA by CT scan will be measured at visits and evaluated centrally. For the overall population and each of the subgroups (Dysglycemic and Type 2 Diabetes Mellitis (T2DM)) from Baseline to Week 12	Baseline, Week 12
Pharmacokinetics - Plasma Trough Concentrations of LIK066	Plasma trough concentrations of LIK066 were measured at Week 12 after daily administrations of LIK066 (2.5, 10, 25 and 50 mg).	Week 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Yokote K, Sano M, Tsumiyama I, Keefe D. Dose-dependent reduction in body weight with LIK066 (licogliflozin) treatment in Japanese patients with obesity. Diabetes Obes Metab. 2020 Jul;22(7):1102-1110. doi: 10.1111/dom.14006. Epub 2020 Mar 12.

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2017
• Primary Completion (Actual): July 25, 2018
• Study Completion (Actual): July 25, 2018

Study Registration Dates

• First Submitted: October 22, 2017
• First Submitted That Met QC Criteria: October 22, 2017
• First Posted (Actual): October 25, 2017

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Weight loss; T2DM; Over weight; interventional study; Obesity disease
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Licogliflozin
• Other Study ID Numbers: CLIK066B1201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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