Trial Outcomes & Findings for Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in NAFLD Patients (NCT NCT01811472)

Last Updated: 2016-02-04

Results Overview

Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

From baseline to week 24

Results posted on

2016-02-04

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Overall Study STARTED	20	11	21
Overall Study COMPLETED	18	11	16
Overall Study NOT COMPLETED	2	0	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Overall Study Adverse Event	1	4
Overall Study Lost to Follow-up	0	1
Overall Study Subject/guardian decision	1	0

Baseline Characteristics

Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in NAFLD Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=21 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Total n=52 Participants Total of all reporting groups
Age, Continuous	55.9 Years STANDARD_DEVIATION 7.69 • n=5 Participants	58.7 Years STANDARD_DEVIATION 6.56 • n=7 Participants	47.7 Years STANDARD_DEVIATION 11.76 • n=5 Participants	53.2 Years STANDARD_DEVIATION 10.32 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants	26 Participants n=4 Participants

PRIMARY outcome

Timeframe: From baseline to week 24

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with baseline and post-baseline value at week 24 are included in this analysis.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=10 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=17 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24	0.00 Percentage of liver fat Interval -1.63 to 1.63	-1.68 Percentage of liver fat Interval -3.93 to 0.56	-2.89 Percentage of liver fat Interval -4.59 to -1.18

SECONDARY outcome

Timeframe: From baseline to week 12

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=19 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 12	-0.80 Percentage of liver fat Interval -2.31 to 0.72	-1.71 Percentage of liver fat Interval -3.79 to 0.37	-2.98 Percentage of liver fat Interval -4.55 to -1.42

SECONDARY outcome

Timeframe: At week 12

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing percent liver fat at week 12 were included in this endpoint analysis.

The response criteria are defined as: a. A reduction of ≥ 30% from baseline in liver fat b. A reduction of ≥ 50% from baseline in liver fat c. Liver fat content \< 10% d. Liver fat content \< 5.6%. Percentage is calculated as (m/n)\*100 where m: number of patients who are responders. n: number of patients with non-missing percent liver fat at that visit.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=19 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Percentage of Responders at Week 12 At least 30% reduction in percent liver fat	10.00 Percentage of responders	18.18 Percentage of responders	31.58 Percentage of responders
Percentage of Responders at Week 12 At least 50% reduction in percent liver fat	5.00 Percentage of responders	0.00 Percentage of responders	21.05 Percentage of responders
Percentage of Responders at Week 12 Liver fat content < 10%	5.00 Percentage of responders	18.18 Percentage of responders	36.84 Percentage of responders
Percentage of Responders at Week 12 Liver fat content <5.6%	0.00 Percentage of responders	0.00 Percentage of responders	21.05 Percentage of responders

SECONDARY outcome

Timeframe: From baseline to week 24

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing percent liver fat at week 24 were included in this endpoint analysis.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=10 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=17 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Percentage of Responders at Week 24 At least 30% reduction in percent liver fat	10.53 Percentage of responders	30.00 Percentage of responders	35.29 Percentage of responders
Percentage of Responders at Week 24 At least 50% reduction in percent liver fat	0.00 Percentage of responders	0.00 Percentage of responders	17.65 Percentage of responders
Percentage of Responders at Week 24 Liver fat content < 10%	5.26 Percentage of responders	20.00 Percentage of responders	52.94 Percentage of responders
Percentage of Responders at Week 24 Liver fat content <5.6%	0.00 Percentage of responders	0.00 Percentage of responders	17.65 Percentage of responders

SECONDARY outcome

Timeframe: From Baseline to week 6

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing liver enzyme values at different timepoint were included in this endpoint analysis.

Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization). Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=20 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6 Liver enzyme: Gamma glutamyl transferase (GGT)	-13.9 U/L Interval -22.1 to -5.7	-7.0 U/L Interval -18.1 to 4.0	-0.9 U/L Interval -9.1 to 7.3
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6 Liver enzyme: Alanine aminotransferase (ALT)	-2.6 U/L Interval -10.6 to 5.3	1.4 U/L Interval -9.2 to 12.1	-9.1 U/L Interval -17.0 to -1.1
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6 Liver enzyme: Aspartate aminotransferase (AST)	2.9 U/L Interval -2.1 to 7.9	4.7 U/L Interval -2.0 to 11.5	-2.5 U/L Interval -7.5 to 2.5

SECONDARY outcome

Timeframe: From Baseline to week 12

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing liver enzyme values at week 12 were included in this endpoint analysis.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=20 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12 Liver enzyme: Alanine aminotransferase (ALT)	-0.6 U/L Interval -10.3 to 9.1	2.9 U/L Interval -10.2 to 16.0	-3.7 U/L Interval -13.8 to 6.4
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12 Liver enzyme: Aspartate aminotransferase (AST)	5.7 U/L Interval -0.9 to 12.3	8.9 U/L Interval 0.0 to 17.7	-0.1 U/L Interval -7.1 to 6.9
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12 Liver enzyme: Gamma glutamyl transferase (GGT)	-0.4 U/L Interval -21.5 to 20.8	-6.0 U/L Interval -34.4 to 22.5	12.0 U/L Interval -10.4 to 34.5

SECONDARY outcome

Timeframe: From Baseline to week 24

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing liver enzyme values at week 24 were included in this endpoint analysis.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=20 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24 Liver enzyme: Alanine aminotransferase (ALT)	-5.3 U/L Interval -12.4 to 1.8	-1.0 U/L Interval -10.4 to 8.3	-10.0 U/L Interval -17.5 to -2.5
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24 Liver enzyme: Aspartate aminotransferase (AST)	-1.8 U/L Interval -7.9 to 4.3	2.5 U/L Interval -5.4 to 10.4	-3.2 U/L Interval -9.6 to 3.3
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24 Liver enzyme: Gamma glutamyl transferase (GGT)	-11.6 U/L Interval -22.2 to -1.0	-8.3 U/L Interval -22.3 to 5.7	0.1 U/L Interval -11.1 to 11.3

SECONDARY outcome

Timeframe: Baseline, week 6, week 12 and week 24

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing liver enzyme values at different timepoints were included in this endpoint analysis.

Normalized liver enzymes defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 40 U/L. Normal/High categories at baseline are defined by criteria of normal. Better is defined as high' at baseline and 'normal' post-dose; Same is defined as 'normal' at baseline and 'normal' post-dose or 'high' at baseline and 'high' post-dose; Worse is defined as 'normal' at baseline and 'high' post-dose.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=20 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Percentage of Patients With Normalized Liver Enzymes Better, week 6	10.0 Percentage of patients	0.0 Percentage of patients	10.0 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Same, week 6	85.0 Percentage of patients	90.9 Percentage of patients	85.0 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Worse, week 6	5.0 Percentage of patients	9.1 Percentage of patients	5.0 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Better, week 12	5.0 Percentage of patients	9.1 Percentage of patients	17.6 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Same, week 12	90.0 Percentage of patients	72.7 Percentage of patients	64.7 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Worse, week 12	5.0 Percentage of patients	18.2 Percentage of patients	17.6 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Better, week 24	5.3 Percentage of patients	18.2 Percentage of patients	17.6 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Same, week 24	89.5 Percentage of patients	72.7 Percentage of patients	58.8 Percentage of patients
Percentage of Patients With Normalized Liver Enzymes Worse, week 24	5.3 Percentage of patients	9.1 Percentage of patients	23.5 Percentage of patients

SECONDARY outcome

Timeframe: Baseline, 6, 12 and 24 weeks

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing values at different timepoints were included in this endpoint analysis

Blood samples were collected for a fasting triglycerides (TG) after a 10-hour (overnight) fast. Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline. Baseline is defined as the value collected at Week 0 (randomization).

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=21 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Percent Change From Baseline in Fasting Triglycerides Change From Baseline to week 6 (n= 20,11, 20)	-14.6 percent change Interval -26.5 to -0.8	-16.0 percent change Interval -31.3 to 2.8	3.2 percent change Interval -11.1 to 19.8
Percent Change From Baseline in Fasting Triglycerides Change From Baseline to week 12 (n = 20,11,17)	-7.3 percent change Interval -18.2 to 5.2	-7.9 percent change Interval -22.3 to 9.1	-15.8 percent change Interval -26.5 to -3.5
Percent Change From Baseline in Fasting Triglycerides Change From Baseline to week 24 (n= 19,11,17)	13.0 percent change Interval -3.8 to 32.6	-10.0 percent change Interval -27.3 to 11.3	-2.4 percent change Interval -17.6 to 15.5

SECONDARY outcome

Timeframe: Baseline, 6 and 24 weeks

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with non-missing values at different timepoints were included in this endpoint analysis

Post-prandial peak triglycerides is reported as maximum triglyceride value over 0-8 hours. Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model. Baseline is defined as the value collected at Week 0 (randomization).

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=21 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Post-prandial Peak Triglycerides Over 0 - 8 Hours Baseline (n= 20, 11, 21)	394.0 mg/dL Interval 364.8 to 425.5	370.2 mg/dL Interval 333.8 to 410.6	375.9 mg/dL Interval 348.8 to 405.1
Post-prandial Peak Triglycerides Over 0 - 8 Hours Week 6 (n = 20,11,20)	336.0 mg/dL Interval 296.8 to 380.4	309.7 mg/dL Interval 262.1 to 366.0	374.1 mg/dL Interval 330.7 to 423.3
Post-prandial Peak Triglycerides Over 0 - 8 Hours Week 24 (n= 20, 11, 15)	401.5 mg/dL Interval 346.6 to 465.0	305.7 mg/dL Interval 205.9 to 372.5	351.8 mg/dL Interval 299.0 to 378.9

SECONDARY outcome

Timeframe: Baseline, 12 and 24 weeks

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with both baseline and post-baseline values at different timepoints were included in this endpoint analysis

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=21 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Change From Baseline in Body Weight Change from baseline to week 12 (n=20, 11, 17)	-1.3 kilogram (kg) Interval -2.0 to -0.5	-2.2 kilogram (kg) Interval -3.2 to -1.2	-2.4 kilogram (kg) Interval -3.2 to -1.6
Change From Baseline in Body Weight Change from baseline to week 24 (n=18, 11, 17)	-1.1 kilogram (kg) Interval -2.5 to 0.4	-2.8 kilogram (kg) Interval -4.7 to -1.0	-2.5 kilogram (kg) Interval -4.0 to -1.1

SECONDARY outcome

Timeframe: Baseline, 12 and 24 weeks

Population: Full analysis set included all patients to whom study treatment was assigned excluding patients who were miss-randomized and did not take investigational drug. Patients with both baseline and post-baseline values at different timepoints were included in this endpoint analysis

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=21 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Change From Baseline in Waist Circumference Change from baseline to week 12 (n=20, 11, 17)	-0.4 centimeter (cm) Interval -2.3 to 1.6	-3.7 centimeter (cm) Interval -6.4 to -1.0	-4.2 centimeter (cm) Interval -6.3 to -2.1
Change From Baseline in Waist Circumference Change from baseline to week 24 (n=19, 11, 17)	-1.7 centimeter (cm) Interval -3.9 to 0.6	-3.7 centimeter (cm) Interval -6.7 to -0.6	-4.2 centimeter (cm) Interval -6.6 to -1.9

SECONDARY outcome

Timeframe: 24 weeks

Population: Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg/10mg n=11 Participants Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20mg n=21 Participants Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability Patients with any adverse event	14 Patients	9 Patients	20 Patients
Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability Patients with at least one SAE	3 Patients	1 Patients	2 Patients
Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability Death	0 Patients	0 Patients	0 Patients

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Pradigastat (LCQ908) 5mg /10 mg

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Pradigastat (LCQ908) 10mg/20 mg

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Pooled Pradigastat (LCQ908)

Serious events: 3 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=20 participants at risk Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 5mg /10 mg n=11 participants at risk Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pradigastat (LCQ908) 10mg/20 mg n=21 participants at risk Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.	Pooled Pradigastat (LCQ908) n=32 participants at risk This arm included all patients randomized to pradigastat (LCQ908) 5mg/10 mg and pradigastat (LCQ908)10mg/20 mg
General disorders NON-CARDIAC CHEST PAIN	5.0% 1/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Investigations ALANINE AMINOTRANSFERASE INCREASED	5.0% 1/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	5.0% 1/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.00% 0/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	9.1% 1/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	3.1% 1/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Musculoskeletal and connective tissue disorders LUMBAR SPINAL STENOSIS	5.0% 1/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Nervous system disorders LUMBAR RADICULOPATHY	5.0% 1/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Nervous system disorders SPINAL CLAUDICATION	5.0% 1/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Nervous system disorders SYNCOPE	0.00% 0/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	4.8% 1/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	3.1% 1/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Psychiatric disorders DEPRESSION	0.00% 0/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	4.8% 1/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	3.1% 1/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.
Psychiatric disorders PANIC ATTACK	0.00% 0/20 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	0.00% 0/11 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	4.8% 1/21 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.	3.1% 1/32 Safety set (SAF) - All patients who received at least one dose of study drug and had at least 1 post-baseline safety assessment.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER