A Randomized, Double-blind, Placebo Controlled Study to A... | NCT01514461

NCT01514461

ID	Type	Description	Link
2011-005535-68	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LCQ908 20 mg	Experimental	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet will be followed and recorded in patient diary.	Drug: LCQ908 Drug: Placebo
LCQ908 40 mg	Experimental	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet will be followed and recorded in patient diary.	Drug: LCQ908 Drug: Placebo
Placebo	Placebo Comparator	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet will be followed and recorded in patient diary.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
LCQ908	Drug	LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg	LCQ908 20 mg LCQ908 40 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change in Fasting Triglycerides From Baseline to 12 Weeks	Blood samples were collected for a fasting lipid panel, including triglycerides. If the 12-week value was missing, the measurement value at 12 weeks or the last available post-baseline measurement value during the double-blind treatment period was analyzed. Baseline is defined as the average of fasting triglyceride values taken at day -3 and day 1. Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline.	Baseline to 12 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline or Final Fasting TG < 8.4 mmol/L (750 mg/dL)	Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.	Baseline, 12 weeks, 24 weeks, 52 weeks

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Written informed consent given before any assessment was performed for Period I.
Male and female patients ages at least 18 years of age.
Fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) at Screening.
An established diagnosis of FCS (HLP Type I) confirmed through ultracentrifugation or by documented medical history of a fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) and by documentation of any of the following at Screening or during the Screening Period:
- Confirmed homozygote or compound heterozygote for known loss-of-function mutations in Type I-causing genes (such as LPL, apo C II, GPIHBP1, or LMF1)
- Post heparin plasma LPL activity of ≤ 20% of normal
- Confirmed presence of LPL inactivating antibodies
History of pancreatitis.

Key Exclusion Criteria:

Current pancreatitis, pancreatitis was required to be inactive for at least 1 week prior to the screening Visit.
Treatment with fish oil preparations within 4 weeks prior to randomization.
Treatment with bile acid binding resins (i.e., colesevelam, etc.) within 4 weeks prior to randomization.
Treatment with fibrates within 4 weeks prior to randomization.
Glybera [alipogene tiparvovec (AAV1-LPLS447X)] gene therapy exposure within the two years prior to screening.
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
Any surgical or medical conditions, acute or unstable chronic disease which may, based on the investigator's opinion, jeopardize the patient in case of participation in the study or might significantly alter the absorption, distribution, metabolism or excretion of the study drug.
History of drug or alcohol abuse within the 12 months prior to randomization or evidence of such abuse at screening.
Evidence of liver disease or liver injury as indicated by abnormal liver function tests such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), or serum bilirubin.
Estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2 or history of chronic renal disease.
Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, or any other limitation of participation based on local regulations.
History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive HCG laboratory test.
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 100 days after discontinuation of investigational study drug.

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Seatlle	Washington	98104	United States
Novartis Investigative Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.

Arm/Group Information

ID	Title	Description
BG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
BG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
BG002	LCQ908 40 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00052.9± 10.9 BG00142.3± 13.61 BG00242.7± 10.94 BG003

Age, Customized

Number

Participants

Title

Denominators

Categories

< 65 years

Title	Measurements
	BG00012 BG00115 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0008 BG0017 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change in Fasting Triglycerides From Baseline to 12 Weeks

Blood samples were collected for a fasting lipid panel, including triglycerides. If the 12-week value was missing, the measurement value at 12 weeks or the last available post-baseline measurement value during the double-blind treatment period was analyzed. Baseline is defined as the average of fasting triglyceride values taken at day -3 and day 1. Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline.

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized. The number of randomized patients with non-missing fasting triglycerides values at baseline and Week 12 are included in this analysis.

Posted

Geometric Mean

95% Confidence Interval

percent change

Baseline to 12 weeks

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG002	LCQ908 40 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Units	Counts
Participants	OG00014 OG00114 OG00212

Title

Denominators

Categories

Title	Measurements
	OG00045.6(6.8 to 98.7) OG0013.7(-24.3 to 42.1) OG002-13.9(-38.9 to 21.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	Mixed Model of Repeated Measurements	0.0538		% change from reference treatment	-28.78			2-Sided	95	-55.69	14.46				No	Superiority or Other
OG000 OG002		Mixed Models Analysis

Secondary

Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline or Final Fasting TG < 8.4 mmol/L (750 mg/dL)

Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.

Posted

Number

Percentage of participants

Baseline, 12 weeks, 24 weeks, 52 weeks

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL)

Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.

Posted

Number

Percentage of participants

12 weeks, 24 weeks, 52 weeks

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline

Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.

Posted

Number

Percentage of participants

Baseline, 12 weeks, 24 weeks, 52 weeks

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds

Percentage of patients reaching target values of <1000 mg/dL or target values of < 2000 mg/dL for fasting triglycerides is reported. Pecentage calculated as (m/n)*100; where 'm' The number of patients who reach target values for fasting triglyceride, 'n' the number of patients with non-missing fasting triglyceride.

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.

Posted

Number

Percentage of patients

12 weeks, 24 weeks, 52 weeks

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Percent Change From Baseline in Fasting Triglycerides

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.

Posted

Geometric Mean

95% Confidence Interval

Percent change

Baseline, 24 weeks, 52 weeks

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG002	LCQ908 40 mg

Secondary

Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12

Post prandial peak triglycerides - maximum triglyceride value over 0-24 hours Post prandial triglycerides AUC0-24 - area under the time curve for triglycerides over 0-24 Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressed as a percentage change from baseline. hours

Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized. For each category, the number of randomized patients who have non-missing values are included in this analysis.

Posted

Geometric Mean

95% Confidence Interval

Percent change

0-24 hours at Baseline, Week 12

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax)

Lowest observed blood concentration (Cmin) and observed maximum blood concentration (Cmax) following drug administration derived from non-compartmental analysis using scheduled sampling time for the whole dataset.

Safety set (SAF) consisted of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment

Posted

Mean

Standard Deviation

ng/mL

0, 1, 2, 3, 4, 6, and 24 hours at Week 12

ID	Title	Description
OG000	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 40 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour)

The area under the concentration-time curve from time zero to 24 hours after drug administration was calculated by using linear trapezoidal rule.

Safety set (SAF) consisted of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment

Posted

Mean

Standard Deviation

ng/mL *hr

0, 1, 2, 3, 4, 6, and 24 hours at Week 12

ID	Title	Description
OG000	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 40 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours)

Safety set (SAF) consisted of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Posted

Median

Full Range

hours

0, 1, 2, 3, 4, 6, and 24 hours at Week 12

ID	Title	Description
OG000	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 40 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg)

Average observed blood concentration measured by (AUC0-24)/24.

Safety set (SAF) consisted of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Posted

Mean

Standard Deviation

ng/mL

0, 1, 2, 3, 4, 6, and 24 hours at Week 12

ID	Title	Description
OG000	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 40 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.

Secondary

Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death

Safety set (SAF) consisted of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Posted

Number

Participants

52 weeks

ID	Title	Description
OG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.
OG002	LCQ908 40 mg

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.	6	15	15	15
EG001	LCQ908 20 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet will be followed and recorded in patient diary.	6	15	15	15
EG002	LCQ908 40 mg	In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen was followed. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet was followed and recorded in patient diary.	3	14	14	14

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
CARDIAC ARREST	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
GASTROINTESTINAL DISORDER	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
PANCREATITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0013 affected15 at risk EG0021 affected14 at risk
PANCREATITIS ACUTE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0012 affected15 at risk EG0021 affected14 at risk
HYPERTRANSAMINASAEMIA	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
PNEUMONIA	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
INCISIONAL HERNIA	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
HEPATIC ENZYME INCREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
MALIGNANT PALATE NEOPLASM	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
CEREBRAL HAEMORRHAGE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
FEMORAL ARTERY OCCLUSION	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
CARDIAC ARREST	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
CARDIAC FAILURE	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
CORONARY ARTERY STENOSIS	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
PALPITATIONS	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
SUPRAVENTRICULAR EXTRASYSTOLES	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
DEAFNESS	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
BLEPHARITIS	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
CONJUNCTIVAL HAEMORRHAGE	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
ABDOMINAL DISCOMFORT	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0022 affected14 at risk
ABDOMINAL DISTENSION	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0021 affected14 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0017 affected15 at risk EG0021 affected14 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0012 affected15 at risk EG0021 affected14 at risk
ABDOMINAL RIGIDITY	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
BARRETT'S OESOPHAGUS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
CHANGE OF BOWEL HABIT	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0012 affected15 at risk EG0021 affected14 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
DEFAECATION URGENCY	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
DENTAL CARIES	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected15 at risk EG00112 affected15 at risk EG00210 affected14 at risk
DIVERTICULUM	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
DRY MOUTH	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
DYSPEPSIA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0012 affected15 at risk EG0020 affected14 at risk
ENTERITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
FAECES DISCOLOURED	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
FAECES SOFT	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0021 affected14 at risk
FLATULENCE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0011 affected15 at risk EG0021 affected14 at risk
FREQUENT BOWEL MOVEMENTS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
HYPERCHLORHYDRIA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
INGUINAL HERNIA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
NAUSEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0015 affected15 at risk EG0024 affected14 at risk
PANCREATITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0013 affected15 at risk EG0022 affected14 at risk
RECTAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
TOOTHACHE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
VOMITING	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0016 affected15 at risk EG0024 affected14 at risk
ASTHENIA	General disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0022 affected14 at risk
CYST	General disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
FATIGUE	General disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0012 affected15 at risk EG0020 affected14 at risk
INFLUENZA LIKE ILLNESS	General disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
MALAISE	General disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
PYREXIA	General disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0012 affected15 at risk EG0021 affected14 at risk
CHOLELITHIASIS	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
ALLERGY TO ARTHROPOD STING	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
ALLERGY TO PLANTS	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
FOOD ALLERGY	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
BRONCHITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
CONJUNCTIVITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
CYSTITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
EAR INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
ERYSIPELAS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
GASTROENTERITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected15 at risk EG0012 affected15 at risk EG0021 affected14 at risk
GASTROENTERITIS VIRAL	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
HAND-FOOT-AND-MOUTH DISEASE	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
HORDEOLUM	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
INFLUENZA	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected15 at risk EG0010 affected15 at risk EG0024 affected14 at risk
JOINT ABSCESS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
LARYNGITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
LOCALISED INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected15 at risk EG0012 affected15 at risk EG0024 affected14 at risk
PHARYNGITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
PNEUMONIA	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
RHINITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
SUBCUTANEOUS ABSCESS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
TINEA INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
TOOTH ABSCESS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
TOOTH INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected15 at risk EG0011 affected15 at risk EG0021 affected14 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
CHEST INJURY	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
CONTUSION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
FALL	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
LIGAMENT SPRAIN	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
LIMB INJURY	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
MUSCLE RUPTURE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
POST PROCEDURAL COMPLICATION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
RIB FRACTURE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
SCAR	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
SPORTS INJURY	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
TOOTH FRACTURE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
BLOOD GLUCOSE INCREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
CAROTID BRUIT	Investigations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
HAEMOGLOBIN DECREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
HEPATIC ENZYME INCREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
WEIGHT DECREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0012 affected15 at risk EG0022 affected14 at risk
WEIGHT INCREASED	Investigations	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0012 affected15 at risk EG0020 affected14 at risk
DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
HYPOCALCAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
HYPOGLYCAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
IRON DEFICIENCY	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
VITAMIN D DEFICIENCY	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0013 affected15 at risk EG0021 affected14 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0011 affected15 at risk EG0023 affected14 at risk
BURSITIS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
INTERVERTEBRAL DISC PROTRUSION	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
MUSCLE FATIGUE	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
MYOPATHY	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
NECK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
SJOGREN'S SYNDROME	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
TENDONITIS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0013 affected15 at risk EG0020 affected14 at risk
LIPOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
NEOPLASM SKIN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
PAPILLOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
DIZZINESS	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected15 at risk EG0013 affected15 at risk EG0021 affected14 at risk
DYSGEUSIA	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0021 affected14 at risk
HEADACHE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0014 affected15 at risk EG0021 affected14 at risk
LETHARGY	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
SCIATICA	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0012 affected15 at risk EG0021 affected14 at risk
SYNCOPE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
DEPRESSION	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
INSOMNIA	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
STRESS	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
DYSURIA	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
RENAL FAILURE ACUTE	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0013 affected15 at risk EG0024 affected14 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk
DYSPNOEA EXERTIONAL	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
NASAL CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
SINUS CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
ACNE	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
ALOPECIA	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk
ROSACEA	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
SKIN LESION	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
XANTHOMA	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
HOT FLUSH	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk

ID	Term
C538489	Familial hyperchylomicronemia syndrome
D006951	Hyperlipoproteinemias

ID	Term
C000594809	pradigastat

Units	Counts
Participants	OG00012 OG0019

ID	Term
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases