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

• ClinicalTrials.gov Identifier: NCT02470403
• Recruitment Status: Completed
• First Posted: June 12, 2015
• Results First Posted: May 12, 2017
• Last Update Posted: January 5, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Elevated Body Mass Index	Drug: LIK066; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 181 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: June 5, 2015
• Actual Primary Completion Date: April 4, 2016
• Actual Study Completion Date: April 4, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Part 1: Percent Change in Body Weight From Baseline to Week 12 [ Time Frame: Baseline, Week 12 (Day 85) ]

   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.

2. Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death [ Time Frame: 12 weeks ]
   This endpoint reports patients with at least one AE (any AE), serious AE and death.
3. Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) [ Time Frame: Baseline, 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.

4. Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death [ Time Frame: 2 weeks ]
   This endpoint reports patients with at least one AE (any AE), serious AE and death

Secondary Outcome Measures :

1. Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms [ Time Frame: Baseline, Week 2 ]

   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.

2. Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study [ Time Frame: Day 84 ]
   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.
3. Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study [ Time Frame: Day 84 ]
   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.
4. 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 [ Time Frame: Day 84 ]
   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.
5. 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 [ Time Frame: Day 84 ]
   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.
6. The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study [ Time Frame: Day 84 ]
   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.
7. 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 [ Time Frame: Day 84 ]
   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.
8. Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study [ Time Frame: Day 1, Day 14 ]
   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)
9. Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study [ Time Frame: Day 1, Day 14 ]
   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)
10. Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study [ Time Frame: Day 1, Day 14 ]
    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)
11. Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study [ Time Frame: Day 1, Day 14 ]
    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)
12. The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study [ Time Frame: Day 1, Day 14 ]
    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)
13. The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study [ Time Frame: Day 1, Day 14 ]
    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)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Nebraska

Novartis Investigative Site

Lincoln, Nebraska, United States, 68502

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Study Director; Novartis Pharmaceuticals

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02470403
• Other Study ID Numbers: CLIK066X2201
• First Posted: June 12, 2015
• Results First Posted: May 12, 2017
• Last Update Posted: January 5, 2021
• Last Verified: March 2019

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

dysglycemic, normoglycemic, prediabetes, type 2 diabetes mellitus

Additional relevant MeSH terms:

Body Weight; Licogliflozin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs