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

Primary Purpose

Elevated Body Mass Index

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

LIK066

Placebo

About this trial

This is an interventional other trial for Elevated Body Mass Index focused on measuring dysglycemic, normoglycemic, prediabetes, type 2 diabetes mellitus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part 1: LIK066 150 mg once daily (qd)

Part 1: Placebo once daily

Part 2: LIK066 75 mg twice daily (bid)

Part 2: LIK066 50 mg three times daily (tid)

Part 2: Placebo three times daily

Arm Description

LIK066 150 mg qd within 15 minutes before starting lunch

Matching placebo tablets of LCZ696 150 mg within 15 minutes before starting lunch.

LIK066 75 mg bid before breakfast and dinner

LIK066 50 mg tid before all 3 meals;

Matching placebo tablets tid before meals.

Outcomes

Primary Outcome Measures

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.

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.

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.

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

Secondary Outcome Measures

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.

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.

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.

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.

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

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.

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.

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)

Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study

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)

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)

The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study

The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study

Full Information

NCT ID

NCT02470403

First Posted

June 10, 2015

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02470403

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

June 5, 2015 (Actual)

Primary Completion Date

April 4, 2016 (Actual)

Study Completion Date

April 4, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Elevated Body Mass Index

Keywords

dysglycemic, normoglycemic, prediabetes, type 2 diabetes mellitus

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

181 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: LIK066 150 mg once daily (qd)

Arm Type

Experimental

Arm Description

LIK066 150 mg qd within 15 minutes before starting lunch

Arm Title

Part 1: Placebo once daily

Arm Type

Placebo Comparator

Arm Description

Matching placebo tablets of LCZ696 150 mg within 15 minutes before starting lunch.

Arm Title

Part 2: LIK066 75 mg twice daily (bid)

Arm Type

Experimental

Arm Description

LIK066 75 mg bid before breakfast and dinner

Arm Title

Part 2: LIK066 50 mg three times daily (tid)

Arm Type

Experimental

Arm Description

LIK066 50 mg tid before all 3 meals;

Arm Title

Part 2: Placebo three times daily

Arm Type

Placebo Comparator

Arm Description

Matching placebo tablets tid before meals.

Intervention Type

Drug

Intervention Name(s)

LIK066

Intervention Description

LIK066 25 mg tablets

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo tablets

Primary Outcome Measure Information:

Title

Part 1: Percent Change in Body Weight From Baseline to Week 12

Description

Time Frame

Baseline, Week 12 (Day 85)

Title

Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death

Description

This endpoint reports patients with at least one AE (any AE), serious AE and death.

Time Frame

12 weeks

Title

Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14)

Description

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.

Time Frame

Baseline, Week 2 (Day 14)

Title

Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death

Description

This endpoint reports patients with at least one AE (any AE), serious AE and death

Time Frame

2 weeks

Secondary Outcome Measure Information:

Title

Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms

Description

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.

Time Frame

Baseline, Week 2

Title

Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study

Description

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.

Time Frame

Day 84

Title

Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study

Description

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.

Time Frame

Day 84

Title

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

Description

Time Frame

Day 84

Title

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

Description

Time Frame

Day 84

Title

The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study

Description

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.

Time Frame

Day 84

Title

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

Description

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.

Time Frame

Day 84

Title

Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study

Description

Time Frame

Day 1, Day 14

Title

Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study

Description

Time Frame

Day 1, Day 14

Title

Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study

Description

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)

Time Frame

Day 1, Day 14

Title

Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study

Description

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)

Time Frame

Day 1, Day 14

Title

The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study

Description

Time Frame

Day 1, Day 14

Title

The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study

Description

Time Frame

Day 1, Day 14

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68502

Country

United States

12. IPD Sharing Statement

Links:

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=172

Description

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

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

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