Effect of LIK066 on Body Weight in Patients With Elevated Body Mass Index

A Randomized, Double-blind, Placebo-controlled, Parallel Group, 2-part Study Investigating the Effect of LIK066 on Body Weight in Dysglycemic (Prediabetes or Type 2 Diabetes) and Normoglycemic Patients With Elevated Body Mass Index

A 12-week study to assess LIK066 effect on body weight in diabetics, prediabetics and normoglycemic patients with elevated body mass index (BMI)

Study Overview

• Status: Completed
• Conditions: Elevated Body Mass Index
• Intervention / Treatment: Drug: Placebo; Drug: LIK066

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Subjects with stable health condition as determined by past medical history, physical examination, electrocardiogram, and laboratory tests at screening.
• Patients with dysglycemia are patients with: Fasting plasma glucose >100mg/dL (5.6 mmol/L), or HbA1c > 5.7% and < 10% at screening.
• Fasting plasma glucose ≤250mg/dL (13.9 mmol/L) at screening.
• If treated with antidiabetic medications (other than prohibited medications), patients must be on a stable dose for 12 weeks prior to randomization and maintain the dose until the end of the study.
• Subjects must have a body mass index (BMI) within the range of 35 - 50 kg/m2 at screening, with stable body weight (± 5 kg) within 3 months prior to screening

Key Exclusion Criteria:

• Pre-existing, clinically significant gastrointestinal, liver, cardiovascular, renal or other chronic medical condition which is considered serious or unstable, other than stable cardiovascular disease, treated hypertension, dyslipidemia or other stable chronic disorders
• Clinically significant GI disorder related to malabsorption or that may affect drug or glucose absorption or history of significant gastrointestinal surgery that could affect intestinal glucose absorption
• Enrollment in a diet, weight loss or exercise programs with the specific intent of losing weight, within 3 months prior to randomization, or clinical diagnosis of any eating disorder
• Pregnant or nursing (lactating) women, and women of child-bearing potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: LIK066 150 mg once daily (qd); LIK066 150 mg qd within 15 minutes before starting lunch	Drug: LIK066; LIK066 25 mg tablets
Placebo Comparator: Part 1: Placebo once daily; Matching placebo tablets of LCZ696 150 mg within 15 minutes before starting lunch.	Drug: LIK066; LIK066 25 mg tablets
Experimental: Part 2: LIK066 75 mg twice daily (bid); LIK066 75 mg bid before breakfast and dinner	Drug: Placebo; Matching placebo tablets
Experimental: Part 2: LIK066 50 mg three times daily (tid); LIK066 50 mg tid before all 3 meals;	Drug: Placebo; Matching placebo tablets
Placebo Comparator: Part 2: Placebo three times daily; Matching placebo tablets tid before meals.	Drug: LIK066; LIK066 25 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Percent Change in Body Weight From Baseline to Week 12	Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is Day -1 in Part 1. Percent change is calculated as [(post baseline- Baseline) /Baseline] * 100. A longitudinal mixed effects model for percent change in body weight was used. The model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by- time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, and the treatment-by-time-by-glycemic status interaction, and Baseline body weight as a covariate.	Baseline, Week 12 (Day 85)
Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death	This endpoint reports patients with at least one AE (any AE), serious AE and death.	12 weeks
Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14)	Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Part 1: Baseline is defined as Day -1. Part 2: Baseline is defined as Day 1 predose. Percent change is calculated as [(post baseline- Baseline) /Baseline] * 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate.	Baseline, Week 2 (Day 14)
Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death	This endpoint reports patients with at least one AE (any AE), serious AE and death	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms	Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is defined as Day 1 predose. Percent change is calculated as [(post baseline- Baseline) /Baseline] * 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate.	Baseline, Week 2
Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study	Blood samples were collected at predose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h postdose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.	Day 84
Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.	Day 84
Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation.	Day 84
Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation.	Day 84
The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.	Day 84
The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.	Day 84
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Cmax at steady state (Cmax, ss)	Day 1, Day 14
Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Tmax at steady state (Tmax, ss)	Day 1, Day 14
Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUClast at steady state (AUClast, ss)	Day 1, Day 14
Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUCtau at steady state (AUCtau, ss)	Day 1, Day 14
The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports CLss/F at steady state (CLss/F, ss)	Day 1, Day 14
The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study	Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Vz/F at steady state (Vz/F, ss)	Day 1, Day 14

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2015
• Primary Completion (Actual): April 4, 2016
• Study Completion (Actual): April 4, 2016

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 11, 2015
• First Posted (Estimate): June 12, 2015

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: dysglycemic, normoglycemic, prediabetes, type 2 diabetes mellitus
• Additional Relevant MeSH Terms: Body Weight; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Licogliflozin
• Other Study ID Numbers: CLIK066X2201