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A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01514461
Collaborator
(none)
45
Enrollment
14
Locations
3
Arms
22
Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether LCQ908 is effective and safe in lowering triglycerides in subjects with Familial Chylomicronemia Syndrome (FCS) (Hyperlipoproteinemia [HLP] type I). Data from this study will be used to support a registration submission of LCQ908 20 mg and 40 mg as treatment of chylomicronemia in subjects with FCS (HLP Type 1).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
Study Start Date :
Jul 1, 2012
Actual Primary Completion Date :
May 1, 2014
Actual Study Completion Date :
May 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: LCQ908
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg

Drug: Placebo
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Other Names:
  • LCQ908

    		•
    Experimental: 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 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
    LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg

    Drug: Placebo
    LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
    Other Names:
  • LCQ908

    		•
    Placebo Comparator: 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 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
    LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
    Other Names:
  • LCQ908

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percent Change in Fasting Triglycerides From Baseline to 12 Weeks [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.

    Secondary Outcome Measures

    1. 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) [Baseline, 12 weeks, 24 weeks, 52 weeks]

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

    2. Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) [12 weeks, 24 weeks, 52 weeks]

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

    3. Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline [Baseline, 12 weeks, 24 weeks, 52 weeks]

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

    4. Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds [12 weeks, 24 weeks, 52 weeks]

      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.

    5. Percent Change From Baseline in Fasting Triglycerides [Baseline, 24 weeks, 52 weeks]

    6. Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 [0-24 hours at Baseline, 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

    7. Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax) [0, 1, 2, 3, 4, 6, and 24 hours at Week 12]

      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.

    8. Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour) [0, 1, 2, 3, 4, 6, and 24 hours at Week 12]

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

    9. Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours) [0, 1, 2, 3, 4, 6, and 24 hours at Week 12]

    10. Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg) [0, 1, 2, 3, 4, 6, and 24 hours at Week 12]

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

    11. Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death [52 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    1. Written informed consent given before any assessment was performed for Period I.

    2. Male and female patients ages at least 18 years of age.

    3. Fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) at Screening.

    4. 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

    1. History of pancreatitis.
    Key Exclusion Criteria:

    1. Current pancreatitis, pancreatitis was required to be inactive for at least 1 week prior to the screening Visit.

    2. Treatment with fish oil preparations within 4 weeks prior to randomization.

    3. Treatment with bile acid binding resins (i.e., colesevelam, etc.) within 4 weeks prior to randomization.

    4. Treatment with fibrates within 4 weeks prior to randomization.

    5. Glybera [alipogene tiparvovec (AAV1-LPLS447X)] gene therapy exposure within the two years prior to screening.

    6. 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.

    7. 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.

    8. History of drug or alcohol abuse within the 12 months prior to randomization or evidence of such abuse at screening.

    9. 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.

    10. Estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2 or history of chronic renal disease.

    11. 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.

    12. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.

    13. 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.

    14. 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 and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Seatlle Washington United States 98104
    2 Novartis Investigative Site Chicoutimi Quebec Canada G7H 7P2
    3 Novartis Investigative Site Ste-Foy Quebec Canada G1V4M6
    4 Novartis Investigative Site Ouest-Montreal Canada H2W1R7
    5 Novartis Investigative Site Bron France 69677
    6 Novartis Investigative Site Nantes France 44093
    7 Novartis Investigative Site Paris Cedex 13 France 75651
    8 Novartis Investigative Site Hamburg Germany 20246
    9 Novartis Investigative Site Köln Germany 50937
    10 Novartis Investigative Site Meibergdreef 9 Netherlands 1105 AZ
    11 Novartis Investigative Site Cape Town South Africa 7925
    12 Novartis Investigative Site Malaga Andalucia Spain 29010
    13 Novartis Investigative Site Sevilla Andalucia Spain 41013
    14 Novartis Investigative Site Manchester United Kingdom M13 9NT

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01514461
    Other Study ID Numbers:
    • CLCQ908B2302
    • 2011-005535-68
    First Posted:
    Jan 23, 2012
    Last Update Posted:
    Jun 3, 2015
    Last Verified:
    May 1, 2015
    Keywords provided by Novartis Pharmaceuticals
    Hyperlipoproteinemia (HLP Type I)
    Fasting Triglycerides
    Additional relevant MeSH terms:
    Hyperlipoproteinemia Type I
    Syndrome

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Period Title: Overall Study
    STARTED 15 15 15
    COMPLETED 10 12 11
    NOT COMPLETED 5 3 4

    Baseline Characteristics

    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg Total
    Arm/Group Description 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. 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. 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. Total of all reporting groups
    Overall Participants 15 15 15 45
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    52.9
    (10.9)
    42.3
    (13.61)
    42.7
    (10.94)
    45.9
    (12.63)
    Age, Customized (Number) [Number]
    < 65 years
    12
    80%
    15
    100%
    15
    100%
    42
    93.3%
    >=65 years
    3
    20%
    0
    0%
    0
    0%
    3
    6.7%
    Sex: Female, Male (Count of Participants)
    Female
    8
    53.3%
    7
    46.7%
    4
    26.7%
    19
    42.2%
    Male
    7
    46.7%
    8
    53.3%
    11
    73.3%
    26
    57.8%

    Outcome Measures

    1. Primary Outcome
    Title Percent Change in Fasting Triglycerides From Baseline to 12 Weeks
    Description 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.
    Time Frame Baseline to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo LCQ908 20mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 14 14 12
    Geometric Mean (95% Confidence Interval) [percent change]
    45.6
    3.7
    -13.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, LCQ908 20mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0538
    Comments
    Method Mixed Models Analysis
    Comments Mixed Model of Repeated Measurements
    Method of Estimation Estimation Parameter % change from reference treatment
    Estimated Value -28.78
    Confidence Interval (2-Sided) 95%
    -55.69 to 14.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, LCQ908 40 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0182
    Comments
    Method Mixed Models Analysis
    Comments Mixed Model of Repeated Measurements
    Method of Estimation Estimation Parameter % change from reference treatment
    Estimated Value -40.88
    Confidence Interval (2-Sided) 95%
    -63.99 to -2.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title 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)
    Description Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
    Time Frame Baseline, 12 weeks, 24 weeks, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 15 15 15
    Week 12 (n = 14, 14, 12)
    14.3
    95.3%
    21.4
    142.7%
    50.0
    333.3%
    Week 24 (n = 13, 14, 12)
    30.8
    205.3%
    35.7
    238%
    33.3
    222%
    Week 52 (n = 11, 14, 11)
    18.2
    121.3%
    21.4
    142.7%
    27.3
    182%
    3. Secondary Outcome
    Title Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL)
    Description Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
    Time Frame 12 weeks, 24 weeks, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 15 15 15
    Week 12 (n = 14, 14, 12)
    14.3
    95.3%
    14.3
    95.3%
    33.3
    222%
    Week 24 (n = 13, 14, 12)
    30.8
    205.3%
    14.3
    95.3%
    16.7
    111.3%
    Week 52 (n = 11, 14, 11)
    18.2
    121.3%
    14.3
    95.3%
    18.2
    121.3%
    4. Secondary Outcome
    Title Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline
    Description Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
    Time Frame Baseline, 12 weeks, 24 weeks, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 15 15 15
    Week 12 (n = 14, 14, 12)
    0.0
    0%
    14.3
    95.3%
    25.0
    166.7%
    Week 24 (n = 13, 14, 12)
    15.4
    102.7%
    28.6
    190.7%
    16.7
    111.3%
    Week 52 (n = 11, 14, 11)
    0.0
    0%
    14.3
    95.3%
    27.3
    182%
    5. Secondary Outcome
    Title Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds
    Description 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.
    Time Frame 12 weeks, 24 weeks, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 15 15 15
    TG < 1000 mg/dL, week 12 (n=14,14,12)
    14.3
    21.4
    33.3
    TG < 1000 mg/dL, week 24 (n=13,14,12)
    30.8
    21.4
    25.0
    TG < 1000 mg/dL, week 52 (n=11,14,11)
    27.3
    14.3
    36.4
    TG < 2000 mg/dL, week 12 (n=14,14,12)
    35.7
    50.0
    83.3
    TG < 2000 mg/dL, week 24 (n=13,14,12)
    38.5
    57.1
    58.3
    TG < 2000 mg/dL, week 52 (n=11,14,11)
    36.4
    50.0
    63.6
    6. Secondary Outcome
    Title Percent Change From Baseline in Fasting Triglycerides
    Description
    Time Frame Baseline, 24 weeks, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 15 15 15
    Week 24 (n=13, 14, 12)
    4.9
    -15.8
    5.5
    Week 52 (n=11, 14, 11)
    15.2
    -6.7
    4.9
    7. Secondary Outcome
    Title Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12
    Description 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
    Time Frame 0-24 hours at Baseline, Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 15 15 15
    Triglycerides (Peak 0-24h) [n=12, 12, 11)
    56.9
    8.6
    6.3
    Triglycerides (AUC 0-24h) [n=12, 12, 11)
    44.5
    0.8
    2.8
    8. Secondary Outcome
    Title Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax)
    Description 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.
    Time Frame 0, 1, 2, 3, 4, 6, and 24 hours at Week 12

    Outcome Measure Data

    Analysis Population Description
    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
    Arm/Group Title LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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.
    Measure Participants 12 9
    Cmin
    312
    (120)
    426
    (224)
    Cmax
    603
    (244)
    745
    (408)
    9. Secondary Outcome
    Title Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour)
    Description The area under the concentration-time curve from time zero to 24 hours after drug administration was calculated by using linear trapezoidal rule.
    Time Frame 0, 1, 2, 3, 4, 6, and 24 hours at Week 12

    Outcome Measure Data

    Analysis Population Description
    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
    Arm/Group Title LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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.
    Measure Participants 12 9
    Mean (Standard Deviation) [ng/mL *hr]
    11000
    (4100)
    14300
    (7390)
    10. Secondary Outcome
    Title Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours)
    Description
    Time Frame 0, 1, 2, 3, 4, 6, and 24 hours at Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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.
    Measure Participants 12 9
    Median (Full Range) [hours]
    6
    8
    11. Secondary Outcome
    Title Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg)
    Description Average observed blood concentration measured by (AUC0-24)/24.
    Time Frame 0, 1, 2, 3, 4, 6, and 24 hours at Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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.
    Measure Participants 12 9
    Mean (Standard Deviation) [ng/mL]
    459
    (171)
    597
    (308)
    12. Secondary Outcome
    Title Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death
    Description
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    Measure Participants 15 15 14
    At least one adverse events
    15
    100%
    15
    100%
    14
    93.3%
    At least one serious adverse event
    6
    40%
    6
    40%
    3
    20%
    Death
    1
    6.7%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description 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.
    Arm/Group Title Placebo LCQ908 20 mg LCQ908 40 mg
    Arm/Group Description 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. 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. 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.
    All Cause Mortality
    Placebo LCQ908 20 mg LCQ908 40 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo LCQ908 20 mg LCQ908 40 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/15 (40%) 6/15 (40%) 3/14 (21.4%)
    Cardiac disorders
    CARDIAC ARREST 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    Gastrointestinal disorders
    ABDOMINAL PAIN 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    GASTROINTESTINAL DISORDER 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    PANCREATITIS 2/15 (13.3%) 3/15 (20%) 1/14 (7.1%)
    PANCREATITIS ACUTE 2/15 (13.3%) 2/15 (13.3%) 1/14 (7.1%)
    Hepatobiliary disorders
    HYPERTRANSAMINASAEMIA 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Infections and infestations
    PNEUMONIA 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Injury, poisoning and procedural complications
    INCISIONAL HERNIA 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Investigations
    HEPATIC ENZYME INCREASED 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    Metabolism and nutrition disorders
    HYPERGLYCAEMIA 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    MALIGNANT PALATE NEOPLASM 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Nervous system disorders
    CEREBRAL HAEMORRHAGE 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders
    PULMONARY EMBOLISM 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Vascular disorders
    FEMORAL ARTERY OCCLUSION 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo LCQ908 20 mg LCQ908 40 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/15 (100%) 15/15 (100%) 14/14 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 2/15 (13.3%) 1/15 (6.7%) 0/14 (0%)
    LEUKOPENIA 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    THROMBOCYTOPENIA 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    Cardiac disorders
    CARDIAC ARREST 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    CARDIAC FAILURE 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    CORONARY ARTERY STENOSIS 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    PALPITATIONS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    SUPRAVENTRICULAR EXTRASYSTOLES 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Ear and labyrinth disorders
    DEAFNESS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Eye disorders
    BLEPHARITIS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    CONJUNCTIVAL HAEMORRHAGE 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT 0/15 (0%) 0/15 (0%) 2/14 (14.3%)
    ABDOMINAL DISTENSION 0/15 (0%) 1/15 (6.7%) 1/14 (7.1%)
    ABDOMINAL PAIN 1/15 (6.7%) 7/15 (46.7%) 1/14 (7.1%)
    ABDOMINAL PAIN UPPER 0/15 (0%) 2/15 (13.3%) 1/14 (7.1%)
    ABDOMINAL RIGIDITY 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    BARRETT'S OESOPHAGUS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    CHANGE OF BOWEL HABIT 1/15 (6.7%) 2/15 (13.3%) 1/14 (7.1%)
    CONSTIPATION 1/15 (6.7%) 1/15 (6.7%) 0/14 (0%)
    DEFAECATION URGENCY 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    DENTAL CARIES 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    DIARRHOEA 10/15 (66.7%) 12/15 (80%) 10/14 (71.4%)
    DIVERTICULUM 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    DRY MOUTH 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    DYSPEPSIA 0/15 (0%) 2/15 (13.3%) 0/14 (0%)
    ENTERITIS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    FAECES DISCOLOURED 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    FAECES SOFT 0/15 (0%) 1/15 (6.7%) 1/14 (7.1%)
    FLATULENCE 1/15 (6.7%) 1/15 (6.7%) 1/14 (7.1%)
    FREQUENT BOWEL MOVEMENTS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    GASTROOESOPHAGEAL REFLUX DISEASE 2/15 (13.3%) 0/15 (0%) 0/14 (0%)
    HYPERCHLORHYDRIA 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    INGUINAL HERNIA 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    NAUSEA 1/15 (6.7%) 5/15 (33.3%) 4/14 (28.6%)
    PANCREATITIS 0/15 (0%) 3/15 (20%) 2/14 (14.3%)
    RECTAL HAEMORRHAGE 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    TOOTHACHE 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    VOMITING 0/15 (0%) 6/15 (40%) 4/14 (28.6%)
    General disorders
    ASTHENIA 0/15 (0%) 1/15 (6.7%) 2/14 (14.3%)
    CYST 1/15 (6.7%) 1/15 (6.7%) 0/14 (0%)
    FATIGUE 2/15 (13.3%) 2/15 (13.3%) 0/14 (0%)
    INFLUENZA LIKE ILLNESS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    MALAISE 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    PYREXIA 1/15 (6.7%) 2/15 (13.3%) 1/14 (7.1%)
    Hepatobiliary disorders
    CHOLELITHIASIS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Immune system disorders
    ALLERGY TO ARTHROPOD STING 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    ALLERGY TO PLANTS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    FOOD ALLERGY 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Infections and infestations
    BRONCHITIS 1/15 (6.7%) 0/15 (0%) 1/14 (7.1%)
    CONJUNCTIVITIS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    CYSTITIS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    EAR INFECTION 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    ERYSIPELAS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    GASTROENTERITIS 3/15 (20%) 2/15 (13.3%) 1/14 (7.1%)
    GASTROENTERITIS VIRAL 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    HAND-FOOT-AND-MOUTH DISEASE 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    HORDEOLUM 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    INFLUENZA 3/15 (20%) 0/15 (0%) 4/14 (28.6%)
    JOINT ABSCESS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    LARYNGITIS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    LOCALISED INFECTION 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    NASOPHARYNGITIS 3/15 (20%) 2/15 (13.3%) 4/14 (28.6%)
    PHARYNGITIS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    PNEUMONIA 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    RESPIRATORY TRACT INFECTION 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    RHINITIS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    SUBCUTANEOUS ABSCESS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    TINEA INFECTION 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    TOOTH ABSCESS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    TOOTH INFECTION 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    UPPER RESPIRATORY TRACT INFECTION 3/15 (20%) 1/15 (6.7%) 1/14 (7.1%)
    URINARY TRACT INFECTION 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    Injury, poisoning and procedural complications
    CHEST INJURY 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    CONTUSION 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    FALL 1/15 (6.7%) 0/15 (0%) 1/14 (7.1%)
    LIGAMENT SPRAIN 1/15 (6.7%) 0/15 (0%) 1/14 (7.1%)
    LIMB INJURY 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    MUSCLE RUPTURE 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    POST PROCEDURAL COMPLICATION 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    RIB FRACTURE 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    SCAR 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    SPORTS INJURY 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    TOOTH FRACTURE 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    Investigations
    BLOOD GLUCOSE INCREASED 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    CAROTID BRUIT 1/15 (6.7%) 1/15 (6.7%) 0/14 (0%)
    HAEMOGLOBIN DECREASED 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    HEPATIC ENZYME INCREASED 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    WEIGHT DECREASED 0/15 (0%) 2/15 (13.3%) 2/14 (14.3%)
    WEIGHT INCREASED 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Metabolism and nutrition disorders
    DECREASED APPETITE 0/15 (0%) 2/15 (13.3%) 0/14 (0%)
    DIABETES MELLITUS 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    HYPERGLYCAEMIA 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    HYPOCALCAEMIA 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    HYPOGLYCAEMIA 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    HYPOKALAEMIA 2/15 (13.3%) 0/15 (0%) 0/14 (0%)
    IRON DEFICIENCY 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    VITAMIN D DEFICIENCY 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/15 (0%) 3/15 (20%) 1/14 (7.1%)
    BACK PAIN 1/15 (6.7%) 1/15 (6.7%) 3/14 (21.4%)
    BURSITIS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    INTERVERTEBRAL DISC PROTRUSION 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    MUSCLE FATIGUE 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    MUSCLE SPASMS 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    MUSCULOSKELETAL PAIN 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    MYALGIA 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    MYOPATHY 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    NECK PAIN 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    PAIN IN EXTREMITY 2/15 (13.3%) 0/15 (0%) 0/14 (0%)
    SJOGREN'S SYNDROME 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    TENDONITIS 0/15 (0%) 3/15 (20%) 0/14 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    LIPOMA 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    NEOPLASM SKIN 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    PAPILLOMA 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Nervous system disorders
    DIZZINESS 3/15 (20%) 3/15 (20%) 1/14 (7.1%)
    DYSGEUSIA 0/15 (0%) 1/15 (6.7%) 1/14 (7.1%)
    HEADACHE 1/15 (6.7%) 4/15 (26.7%) 1/14 (7.1%)
    LETHARGY 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    SCIATICA 0/15 (0%) 2/15 (13.3%) 1/14 (7.1%)
    SYNCOPE 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Psychiatric disorders
    DEPRESSION 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    INSOMNIA 2/15 (13.3%) 0/15 (0%) 0/14 (0%)
    STRESS 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Renal and urinary disorders
    DYSURIA 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    RENAL FAILURE ACUTE 1/15 (6.7%) 0/15 (0%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 2/15 (13.3%) 3/15 (20%) 4/14 (28.6%)
    DYSPNOEA 3/15 (20%) 0/15 (0%) 0/14 (0%)
    DYSPNOEA EXERTIONAL 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    NASAL CONGESTION 2/15 (13.3%) 0/15 (0%) 1/14 (7.1%)
    OROPHARYNGEAL PAIN 2/15 (13.3%) 1/15 (6.7%) 0/14 (0%)
    SINUS CONGESTION 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    Skin and subcutaneous tissue disorders
    ACNE 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    ALOPECIA 0/15 (0%) 0/15 (0%) 1/14 (7.1%)
    ROSACEA 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    SKIN LESION 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    XANTHOMA 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    Vascular disorders
    HOT FLUSH 0/15 (0%) 1/15 (6.7%) 0/14 (0%)
    PERIPHERAL ARTERIAL OCCLUSIVE DISEASE 1/15 (6.7%) 0/15 (0%) 0/14 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

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

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email trialandresults.registries@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01514461
    Other Study ID Numbers:
    • CLCQ908B2302
    • 2011-005535-68
    First Posted:
    Jan 23, 2012
    Last Update Posted:
    Jun 3, 2015
    Last Verified:
    May 1, 2015