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Clinical Trial Results:
An open label, 52-week, safety and tolerability extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with Familial Chylomicronemia Syndrome.

Summary
EudraCT number	2012-000802-32
Trial protocol	DE GB ES NL
Global end of trial date	01 Jul 2015

Results information
Results version number	v1(current)
This version publication date	03 Jul 2016
First version publication date	03 Jul 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CLCQ908B2305

ISRCTN number

US NCT number

NCT01589237

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Jul 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Jul 2015

Was the trial ended prematurely?

Yes

Main objective of the trial

To establish the long-term safety and tolerability of pradigastat in a study with optional up titration, comparable to clinical practice, in patients with FCS ( (Familial Chylomicronemia Syndrome) (HLP type I) who discontinued (due to tolerability issues or for reasons other than serious study drug related AEs) or completed study CLCQ908B2302 after 52 weeks.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Feb 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 17

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

United Kingdom: 1

Country: Number of subjects enrolled

Netherlands: 9

Country: Number of subjects enrolled

South Africa: 2

Country: Number of subjects enrolled

United States: 3

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

100% patients who completed the screening phase were enrolled in the study.

Period 1 title

Part A (52 weeks)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo of pradigastat (LCQ908) regimen

Arm description

Part A: Patients who were randomized to placebo in study CLCQ908B2302/NCT01514461. In current study, patients initiated at 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose was allowed. One down titration allowed from the highest dose attained. Part B: Patients who consented to take part in the Part B continued their treatment at the same dose as they took when they completed Part A. LCQ908 treatment could be titrated (within the dose range 10 mg to 40 mg) at the investigators discretion and based on individual patients’ tolerance and safety profile.

Arm type

Placebo

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

20 mg pradigastat (LCQ908) regimen

Arm description

Part A: Patients who were randomized to LCQ908 20 mg in study CLCQ908B2302/NCT01514461. In current study, patients initiated at LCQ908 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose was allowed. One down titration allowed from the highest dose attained. Part B: Patients who consented to take part in the Part B continued their treatment at the same dose as they took when they completed Part A. LCQ908 treatment could be titrated (within the dose range 10 mg to 40 mg) at the investigators discretion and based on individual patients’ tolerance and safety profile.

Arm type

Experimental

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

40 mg pradigastat (LCQ908) regimen

Arm description

Part A: Patients who were randomized to LCQ908 40 mg in study CLCQ908B2302/NCT01514461. In current study, patients initiated at LCQ908 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose was allowed. One down titration allowed from the highest dose attained. Part B: Part B: Patients who consented to take part in the Part B continued their treatment at the same dose as they took when they completed Part A. LCQ908 treatment could be titrated (within the dose range 10 mg to 40 mg) at the investigators discretion and based on individual patients’ tolerance and safety profile.

Arm type

Experimental

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

pradigastat (LCQ9908) regimen- from study A2212

Arm description

Part A: Patients who were randomized to LCQ908 in study CLCQ908A2212/NCT01146522. In current study, patients initiated at LCQ908 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose was allowed. One down titration allowed from the highest dose attained. Part B: Patients who consented to take part in the Part B continued their treatment at the same dose as they took when they completed Part A. LCQ908 treatment could be titrated (within the dose range 10 mg to 40 mg) at the investigators discretion and based on individual patients’ tolerance and safety profile.

Arm type

Experimental

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

Number of subjects in period 1	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Started	11	12	10	5
Completed	9	9	8	5
Not completed	2	3	2	0
Subject/guardian decision	2	3	2	-

Period 2 title

Part B (planned for 78 week-terminated)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo of pradigastat (LCQ908) regimen

Arm description

Arm type

Placebo

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

20 mg pradigastat (LCQ908) regimen

Arm description

Arm type

Experimental

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

40 mg pradigastat (LCQ908) regimen

Arm description

Arm type

Experimental

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

pradigastat (LCQ908) regimen- from study A2212

Arm description

Arm type

Experimental

Investigational medicinal product name

pradigastat

Investigational medicinal product code

LCQ908

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

starting dose: 10 mg/day pradigastat (LCQ908) with optional up-titration up to 40 mg

Number of subjects in period 2 ^[1]	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ908) regimen- from study A2212
Started	5	6	4	4
Completed	0	0	0	0
Not completed	5	6	4	4
Physician decision	-	-	-	1
Study terminated by sponsor	5	5	4	3
Subject/guardian decision	-	1	-	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all patients who completed Part A consented to continue in Part B of the study.

Baseline characteristics

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Reporting group title

Placebo of pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

20 mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

40 mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

pradigastat (LCQ9908) regimen- from study A2212

Reporting group description

Reporting group values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212	Total
Number of subjects	11	12	10	5	38
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					0
Adolescents (12-17 years)					0
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	52.9 ± 10.22	44.1 ± 14.26	43.6 ± 84.53	52.2 ± 12.72	-
Gender, Male/Female
Units: Participants
Female	5	6	2	3	16
Male	6	6	8	2	22

End points

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Reporting group title

Placebo of pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

20 mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

40 mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

pradigastat (LCQ9908) regimen- from study A2212

Reporting group description

Reporting group title

Placebo of pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

20 mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

40 mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

pradigastat (LCQ908) regimen- from study A2212

Reporting group description

Primary: Number of patients with any Adverse events, Serious Adverse events and death

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End point title

Number of patients with any Adverse events, Serious Adverse events and death ^[1]

End point description

Safety set (SAF) - All subjects who received at least one dose of study drug and had at least one post-baseline safety assessment in this extension study.

End point type

Primary

End point timeframe

52 weeks

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There was no planned statistical analysis for this safety endpoint

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: Participants
At least one Adverse Event (any)	11	12	10	5
At least one serious AE	1	6	2	2
Death	0	0	0	0

No statistical analyses for this end point

Secondary: Changes from baseline in triglyceride levels up to 52 weeks

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End point title

Changes from baseline in triglyceride levels up to 52 weeks

End point description

Blood samples were collected for a fasting lipid panel, including total triglycerides. Lipid measurements were collected after a 12 hour (overnight) fast. The maintenance of effect was assessed on triglyceride levels during continued therapy with LCQ908 for up to 52 weeks. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
Change in week 12 (n=10,11,10,5)	1.63 ± 45.19	-5.8 ± 66.1	43.94 ± 52.66	-19.36 ± 42.82
change in week 24 (n=10,10,9,5)	-14.59 ± 52.33	-36.19 ± 64.8	32.54 ± 87.83	-26.05 ± 31.5
change in week 52 (n=9,8,9,5)	16.46 ± 29.27	-30.03 ± 78.52	92.15 ± 60.21	-9.2 ± 43.34

No statistical analyses for this end point

Secondary: Changes from baseline in Cholesterol levels up to 52 weeks

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End point title

Changes from baseline in Cholesterol levels up to 52 weeks

End point description

Blood samples were collected for a fasting lipid panel, including cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
Change in week 12 (n=10,11,10,5)	-5.58 ± 36.38	-4.76 ± 36.26	18.76 ± 31.54	-10.42 ± 24.68
change in week 24 (n=10,10,9,5)	-10.54 ± 27.87	-21.54 ± 24.98	7.45 ± 37.28	-13.87 ± 25.64
change in week 52 (n=9,8,9,5)	5.75 ± 17.51	-13.76 ± 36.1	40.95 ± 34.1	-6.84 ± 22.55

No statistical analyses for this end point

Secondary: Changes from baseline in HDL and Non HDL cholesterol levels up to 52 weeks

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End point title

Changes from baseline in HDL and Non HDL cholesterol levels up to 52 weeks

End point description

Blood samples were collected for a fasting lipid panel, including HDL and non HDL cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
HDL: Change in week 12 (n=10,11,10,5)	-14.13 ± 30.08	3.37 ± 24.75	-5.99 ± 22.19	-7.09 ± 27.11
Non HDL: change in week 12 (n=10,11,10,5)	-5.37 ± 39.61	-7.72 ± 42.4	20.7 ± 34.18	-10.57 ± 26.16
HDL: change in week 24 (n=10,10,9,5)	-7.11 ± 19.41	-1.83 ± 31.36	6.67 ± 22.19	-15.6 ± 37.69
Non HDL: change in week 24 (n=10,10,9,5)	-11.29 ± 29.53	-25.22 ± 31.49	7.17 ± 40.5	-14.01 ± 28.04
HDL: change in week 52 (n=9,8,9,5)	-10.85 ± 19.78	8.11 ± 29.35	-7.33 ± 27.63	-21.41 ± 22.91
Non HDL: change in week 52 (n=9,8,9,5)	8.06 ± 21.42	-17.68 ± 42.65	45.25 ± 37.45	-6.09 ± 24.59

No statistical analyses for this end point

Secondary: Changes from baseline in glycerol levels up to 52 weeks

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End point title

Changes from baseline in glycerol levels up to 52 weeks

End point description

Blood samples were collected for a fasting lipid panel, including glycerol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
Change in week 12 (n=10,11,10,5)	-26.56 ± 72.88	-15.5 ± 73.33	0.68 ± 75.4	-46.83 ± 105.58
change in week 24 (n=10,10,9,5)	-40 ± 67.28	-46.97 ± 62.46	-36.26 ± 133.58	-56.99 ± 96.06
change in week 52 (n=9,8,9,5)	-38.15 ± 70.1	-31.96 ± 64.76	-28.52 ± 101.85	-37.02 ± 81.67

No statistical analyses for this end point

Secondary: Changes from baseline in free fatty acid levels up to 52 weeks

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End point title

Changes from baseline in free fatty acid levels up to 52 weeks

End point description

Blood samples were collected for a fasting lipid panel, including free fatty acid level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
Change in week 12 (n=10,11,10,5)	-23.11 ± 53.05	-17.85 ± 62.48	53.09 ± 44.83	-46.58 ± 128.38
change in week 24 (n=10,10,9,5)	-20.35 ± 80.16	-30.44 ± 62.01	36.18 ± 64.97	-42.74 ± 108.73
change in week 52 (n=9,8,9,5)	-16.99 ± 43.34	-7.69 ± 54.21	79.15 ± 49.37	-18.29 ± 104.77

No statistical analyses for this end point

Secondary: Changes from baseline in Apolipoprotein A1 levels up to 52 weeks

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End point title

Changes from baseline in Apolipoprotein A1 levels up to 52 weeks

End point description

Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein A1. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
Change in week 12 (n=11,11,10,5)	-3.24 ± 23.82	2.55 ± 15.09	6.58 ± 17.04	2.95 ± 33.54
change in week 24 (n=10,10,10,5)	4.8 ± 14.16	1.41 ± 17.45	5.57 ± 25.69	5.11 ± 28.49
change in week 52 (n=10,8,9,5)	4.51 ± 19.21	10.01 ± 16.28	4.43 ± 19.34	-0.82 ± 16.79

No statistical analyses for this end point

Secondary: Changes from baseline in Apolipoprotein B-48 levels up to 52 weeks

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End point title

Changes from baseline in Apolipoprotein B-48 levels up to 52 weeks

End point description

Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-48. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
Change in week 12 (n=11,11,10,5)	-4.03 ± 79.87	33.24 ± 79.2	109.67 ± 52.5	-30.03 ± 61.78
change in week 24 (n=10,10,10,5)	9.13 ± 30.79	-10.23 ± 58.91	105.52 ± 71.45	-35.04 ± 31.11
change in week 52 (n=10,8,9,5)	56.25 ± 57.65	-22.63 ± 107.21	135.33 ± 71.11	27.75 ± 57.77

No statistical analyses for this end point

Secondary: Changes from baseline in Apolipoprotein B-100 levels up to 52 weeks

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End point title

Changes from baseline in Apolipoprotein B-100 levels up to 52 weeks

End point description

Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-100. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. Full analysis set (FAS) – All subjects in the extension study who were in FAS in either study LCQ908A2212 or LCQ908B2302. At each time point post-baseline, only patients with a value at both baseline and the post-dose time point are included.

End point type

Secondary

End point timeframe

Baseline, Week 12, 24 and 52

End point values	Placebo of pradigastat (LCQ908) regimen	20 mg pradigastat (LCQ908) regimen	40 mg pradigastat (LCQ908) regimen	pradigastat (LCQ9908) regimen- from study A2212
Number of subjects analysed	11	12	10	5
Units: percentage change
geometric mean (geometric coefficient of variation)
Change in week 12 (n=9,11,9,5)	-15.75 ± 41.5	15.1 ± 58.53	-8.34 ± 32.73	3.33 ± 32.46
change in week 24 (n=10,9,10,5)	-2.75 ± 63.1	21.33 ± 38.76	-18.28 ± 52.94	11.68 ± 43.73
change in week 52 (n=10,7,9,5)	-12.52 ± 44.16	25.39 ± 36.77	-10.73 ± 37.2	10.02 ± 39.08

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.

Adverse event reporting additional description

Part B - 40 mg pradigastat (LCQ908) regimen had no adverse event (serious or other).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Part A-placebo of pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

Part A-20mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

Part A-40mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

Part A: pradigastat (LCQ908) regimen- from study A2212

Reporting group description

Reporting group title

Part B-placebo of pradigastat (LCQ908) regimen

Reporting group description

Part B: Patients who consented to take part in the Part B continued their treatment at the same dose as they took when they completed Part A. LCQ908 treatment could be titrated (within the dose range 10 mg to 40 mg) at the investigators discretion and based on individual patients’ tolerance and safety profile.

Reporting group title

Part B-20mg pradigastat (LCQ908) regimen

Reporting group description

Reporting group title

Part B- pradigastat (LCQ908) regimen- from study A2212

Reporting group description

Serious adverse events	Part A-placebo of pradigastat (LCQ908) regimen	Part A-20mg pradigastat (LCQ908) regimen	Part A-40mg pradigastat (LCQ908) regimen	Part A: pradigastat (LCQ908) regimen- from study A2212	Part B-placebo of pradigastat (LCQ908) regimen	Part B-20mg pradigastat (LCQ908) regimen	Part B- pradigastat (LCQ908) regimen- from study A2212
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 11 (9.09%)	6 / 12 (50.00%)	2 / 10 (20.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
CORONARY ARTERY STENOSIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
PANCREATITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PANCREATITIS ACUTE
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
GASTROENTERITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
POSTOPERATIVE WOUND INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
DEHYDRATION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIABETES MELLITUS INADEQUATE CONTROL
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOGLYCAEMIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MALNUTRITION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part A-placebo of pradigastat (LCQ908) regimen	Part A-20mg pradigastat (LCQ908) regimen	Part A-40mg pradigastat (LCQ908) regimen	Part A: pradigastat (LCQ908) regimen- from study A2212	Part B-placebo of pradigastat (LCQ908) regimen	Part B-20mg pradigastat (LCQ908) regimen	Part B- pradigastat (LCQ908) regimen- from study A2212
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 11 (100.00%)	12 / 12 (100.00%)	10 / 10 (100.00%)	5 / 5 (100.00%)	4 / 5 (80.00%)	3 / 6 (50.00%)	3 / 4 (75.00%)
Vascular disorders
AORTIC ANEURYSM
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
HOT FLUSH
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0
HYPERTENSION
subjects affected / exposed	0 / 11 (0.00%)	2 / 12 (16.67%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	1	0	0	0	0
General disorders and administration site conditions
FATIGUE
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	0	0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
THIRST
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
VESSEL PUNCTURE SITE INDURATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Reproductive system and breast disorders
DYSMENORRHOEA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
ERECTILE DYSFUNCTION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0	0
PREMATURE MENOPAUSE
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	0	0
DYSPNOEA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
PHARYNGEAL INFLAMMATION
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0
PNEUMOTHORAX
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
RHINORRHOEA
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Psychiatric disorders
AGITATION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
DEPRESSED MOOD
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
INSOMNIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	1	0	0	0
STRESS
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Investigations
CARDIAC MURMUR
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
CAROTID BRUIT
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
WEIGHT DECREASED
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Injury, poisoning and procedural complications
CONTUSION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
FALL
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
FIBULA FRACTURE
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
LIGAMENT RUPTURE
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
MUSCLE STRAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
POST PROCEDURAL INFLAMMATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
WOUND
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Congenital, familial and genetic disorders
ABNORMAL PALMAR/PLANTAR CREASES
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	1
Cardiac disorders
CARDIAC FAILURE
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Nervous system disorders
APHONIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0
DIZZINESS
subjects affected / exposed	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	1	1	0	3	0	1	0
HEADACHE
subjects affected / exposed	1 / 11 (9.09%)	2 / 12 (16.67%)	2 / 10 (20.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	2	2	1	0	0	0
MIGRAINE
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	1	0	0
PARAESTHESIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
RESTLESS LEGS SYNDROME
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
SCIATICA
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	0
SYNCOPE
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	1	0	0	0
Ear and labyrinth disorders
EAR PAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
VERTIGO POSITIONAL
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
subjects affected / exposed	1 / 11 (9.09%)	2 / 12 (16.67%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	2	1	0	0	0	0
ABDOMINAL DISTENSION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
ABDOMINAL PAIN
subjects affected / exposed	2 / 11 (18.18%)	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)
occurrences all number	5	2	7	0	0	1	2
ABDOMINAL PAIN UPPER
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	1	0	0	0
CONSTIPATION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	0	0
DIARRHOEA
subjects affected / exposed	8 / 11 (72.73%)	11 / 12 (91.67%)	5 / 10 (50.00%)	4 / 5 (80.00%)	2 / 5 (40.00%)	1 / 6 (16.67%)	3 / 4 (75.00%)
occurrences all number	50	41	9	13	4	1	18
DYSPEPSIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
FAECAL INCONTINENCE
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0
FOOD POISONING
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	1	0	0
GASTRITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
NAUSEA
subjects affected / exposed	2 / 11 (18.18%)	4 / 12 (33.33%)	3 / 10 (30.00%)	2 / 5 (40.00%)	2 / 5 (40.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)
occurrences all number	3	5	3	3	2	3	0
PANCREATITIS
subjects affected / exposed	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	6	0	0	0	1	0
PANCREATITIS ACUTE
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
STEATORRHOEA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
TONGUE CYST
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
VOMITING
subjects affected / exposed	1 / 11 (9.09%)	2 / 12 (16.67%)	1 / 10 (10.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	3	1	2	1	0	0
Skin and subcutaneous tissue disorders
ALOPECIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0	0
PSORIASIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
RASH
subjects affected / exposed	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	2	0	0	0
XANTHOMA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
BACK PAIN
subjects affected / exposed	1 / 11 (9.09%)	1 / 12 (8.33%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	2	0	0	0	0
MUSCULOSKELETAL PAIN
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0
MYALGIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0	0
NECK PAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0	0
OSTEOARTHRITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
PAIN IN EXTREMITY
subjects affected / exposed	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	1	0	0
ROTATOR CUFF SYNDROME
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0
SYNOVIAL CYST
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
TENDONITIS
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Infections and infestations
BRONCHITIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
CYSTITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
GASTROENTERITIS
subjects affected / exposed	1 / 11 (9.09%)	2 / 12 (16.67%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	3	0	0	0	0	0
INFLUENZA
subjects affected / exposed	6 / 11 (54.55%)	2 / 12 (16.67%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	7	2	2	0	0	0	0
LUNG INFECTION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
NASOPHARYNGITIS
subjects affected / exposed	4 / 11 (36.36%)	4 / 12 (33.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	2 / 5 (40.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	5	4	0	1	2	2	0
PNEUMONIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	0
POST PROCEDURAL INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
SINUSITIS
subjects affected / exposed	1 / 11 (9.09%)	2 / 12 (16.67%)	1 / 10 (10.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	2	1	1	1	0	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 11 (9.09%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	2	0	2	0	0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0
VAGINAL INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0
VULVOVAGINAL MYCOTIC INFECTION
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
GOUT
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
HYPOGLYCAEMIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
HYPOKALAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0
VITAMIN B COMPLEX DEFICIENCY
subjects affected / exposed	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0
VITAMIN D DEFICIENCY
subjects affected / exposed	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

05 Apr 2014

Amendment was issued 25 months after study start was introduced to extend the trial duration of CLCQ908B2305 from 52 weeks to 130 weeks to allow the patients in LCQ908B2305 to continue their treatment with pradigastat after they completed the original 52 week study. Following amendment 2, the original 52 week duration became Part A of LCQ908B2305 and the 78 week extension became Part B, together, the total duration of LCQ908B2305 was 130 weeks. In addition, as a part of this amendment, a change was made to allow additional interim analyses during this extended trial as needed for evaluation of efficacy and safety of pradigastat. All changes made to the protocol in amendment 2 had no impact on patient safety, the scientific validity of the trial or overall study objectives. Patients were re-consented with a revised informed consent form for the additional study Part B, as per this amendment.

24 Feb 2015

Amendment was issued almost 3 years after study start was introduced to implement the sponsor’s decision to end the CLCQ908B2305 extension trial (Part B) at the same time as the last patient in Part A completed 52 weeks. The findings from the December 2014 interim analysis suggested that the size of benefit that was anticipated from continued participation of patients in the 18 month extension trial (Part B) no longer supported trial extension beyond Part A.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

As the anticipated benefit from the continued participation of patients in 18 month extension (Part B) was not supported by results of the December 2014 interim analysis, Novartis decided to terminate the Part B to be effective as of May 31, 2015.

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Clinical trials

Clinical Trial Results:
An open label, 52-week, safety and tolerability extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with Familial Chylomicronemia Syndrome.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of patients with any Adverse events, Serious Adverse events and death

Primary: Number of patients with any Adverse events, Serious Adverse events and death

Secondary: Changes from baseline in triglyceride levels up to 52 weeks

Secondary: Changes from baseline in triglyceride levels up to 52 weeks

Secondary: Changes from baseline in Cholesterol levels up to 52 weeks

Secondary: Changes from baseline in Cholesterol levels up to 52 weeks

Secondary: Changes from baseline in HDL and Non HDL cholesterol levels up to 52 weeks

Secondary: Changes from baseline in HDL and Non HDL cholesterol levels up to 52 weeks

Secondary: Changes from baseline in glycerol levels up to 52 weeks

Secondary: Changes from baseline in glycerol levels up to 52 weeks

Secondary: Changes from baseline in free fatty acid levels up to 52 weeks

Secondary: Changes from baseline in free fatty acid levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein A1 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein A1 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-48 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-48 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-100 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-100 levels up to 52 weeks

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Outside EU/EEA

Clinical trials

Clinical Trial Results: An open label, 52-week, safety and tolerability extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with Familial Chylomicronemia Syndrome.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of patients with any Adverse events, Serious Adverse events and death

Primary: Number of patients with any Adverse events, Serious Adverse events and death

Secondary: Changes from baseline in triglyceride levels up to 52 weeks

Secondary: Changes from baseline in triglyceride levels up to 52 weeks

Secondary: Changes from baseline in Cholesterol levels up to 52 weeks

Secondary: Changes from baseline in Cholesterol levels up to 52 weeks

Secondary: Changes from baseline in HDL and Non HDL cholesterol levels up to 52 weeks

Secondary: Changes from baseline in HDL and Non HDL cholesterol levels up to 52 weeks

Secondary: Changes from baseline in glycerol levels up to 52 weeks

Secondary: Changes from baseline in glycerol levels up to 52 weeks

Secondary: Changes from baseline in free fatty acid levels up to 52 weeks

Secondary: Changes from baseline in free fatty acid levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein A1 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein A1 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-48 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-48 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-100 levels up to 52 weeks

Secondary: Changes from baseline in Apolipoprotein B-100 levels up to 52 weeks

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An open label, 52-week, safety and tolerability extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with Familial Chylomicronemia Syndrome.