Familial Chylomicronemia Syndrome (FCS)
Conditions
Keywords
Hyperlipoproteinemia (HLP Type I), Fasting Triglycerides
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).
Interventions
DRUGLCQ908
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
DRUGPlacebo
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 5. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Percent Change From Baseline in Fasting Triglycerides | Baseline, 24 weeks, 52 weeks | — |
| 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 |
| 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. |
| 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. |
| 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 | — |
| 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. |
| Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | 52 weeks | — |
| 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. |
Countries
Canada, France, Germany, Netherlands, South Africa, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 15 |
| 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. | 15 |
| 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. | 15 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 3 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Patient/guardian decision | 1 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | LCQ908 20 mg | LCQ908 40 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 52.9 Years STANDARD_DEVIATION 10.9 | 42.3 Years STANDARD_DEVIATION 13.61 | 42.7 Years STANDARD_DEVIATION 10.94 | 45.9 Years STANDARD_DEVIATION 12.63 |
| Age, Customized < 65 years | 12 Participants | 15 Participants | 15 Participants | 42 Participants |
| Age, Customized >=65 years | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 11 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 15 | 15 / 15 | 14 / 14 |
| serious Total, serious adverse events | 6 / 15 | 6 / 15 | 3 / 14 |
Outcome results
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.
Time frame: Baseline to 12 weeks
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Percent Change in Fasting Triglycerides From Baseline to 12 Weeks | 45.6 percent change |
| LCQ908 20mg | Percent Change in Fasting Triglycerides From Baseline to 12 Weeks | 3.7 percent change |
| LCQ908 40 mg | Percent Change in Fasting Triglycerides From Baseline to 12 Weeks | -13.9 percent change |
p-value: 0.053895% CI: [-55.69, 14.46]Mixed Models Analysis
p-value: 0.018295% CI: [-63.99, -2.94]Mixed Models Analysis
Secondary
Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death
Time frame: 52 weeks
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | At least one serious adverse event | 6 Participants |
| Placebo | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | At least one adverse events | 15 Participants |
| Placebo | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | Death | 1 Participants |
| LCQ908 20mg | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | At least one serious adverse event | 6 Participants |
| LCQ908 20mg | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | At least one adverse events | 15 Participants |
| LCQ908 20mg | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | Death | 0 Participants |
| LCQ908 40 mg | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | At least one adverse events | 14 Participants |
| LCQ908 40 mg | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | Death | 0 Participants |
| LCQ908 40 mg | Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death | At least one serious adverse event | 3 Participants |
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.
Time frame: 12 weeks, 24 weeks, 52 weeks
Population: Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 12 (n=14,14,12) | 14.3 Percentage of patients |
| Placebo | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 24 (n=13,14,12) | 30.8 Percentage of patients |
| Placebo | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 52 (n=11,14,11) | 27.3 Percentage of patients |
| Placebo | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 12 (n=14,14,12) | 35.7 Percentage of patients |
| Placebo | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 24 (n=13,14,12) | 38.5 Percentage of patients |
| Placebo | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 52 (n=11,14,11) | 36.4 Percentage of patients |
| LCQ908 20mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 52 (n=11,14,11) | 50.0 Percentage of patients |
| LCQ908 20mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 12 (n=14,14,12) | 21.4 Percentage of patients |
| LCQ908 20mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 12 (n=14,14,12) | 50.0 Percentage of patients |
| LCQ908 20mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 24 (n=13,14,12) | 57.1 Percentage of patients |
| LCQ908 20mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 24 (n=13,14,12) | 21.4 Percentage of patients |
| LCQ908 20mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 52 (n=11,14,11) | 14.3 Percentage of patients |
| LCQ908 40 mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 24 (n=13,14,12) | 25.0 Percentage of patients |
| LCQ908 40 mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 52 (n=11,14,11) | 36.4 Percentage of patients |
| LCQ908 40 mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 52 (n=11,14,11) | 63.6 Percentage of patients |
| LCQ908 40 mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 12 (n=14,14,12) | 83.3 Percentage of patients |
| LCQ908 40 mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 1000 mg/dL, week 12 (n=14,14,12) | 33.3 Percentage of patients |
| LCQ908 40 mg | Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds | TG < 2000 mg/dL, week 24 (n=13,14,12) | 58.3 Percentage of patients |
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.
Time frame: Baseline, 12 weeks, 24 weeks, 52 weeks
Population: Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 24 (n = 13, 14, 12) | 15.4 Percentage of participants |
| Placebo | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 12 (n = 14, 14, 12) | 0.0 Percentage of participants |
| Placebo | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 52 (n = 11, 14, 11) | 0.0 Percentage of participants |
| LCQ908 20mg | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 24 (n = 13, 14, 12) | 28.6 Percentage of participants |
| LCQ908 20mg | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 12 (n = 14, 14, 12) | 14.3 Percentage of participants |
| LCQ908 20mg | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 52 (n = 11, 14, 11) | 14.3 Percentage of participants |
| LCQ908 40 mg | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 12 (n = 14, 14, 12) | 25.0 Percentage of participants |
| LCQ908 40 mg | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 52 (n = 11, 14, 11) | 27.3 Percentage of participants |
| LCQ908 40 mg | Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline | Week 24 (n = 13, 14, 12) | 16.7 Percentage of participants |
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.
Time frame: Baseline, 12 weeks, 24 weeks, 52 weeks
Population: Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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) | Week 24 (n = 13, 14, 12) | 30.8 Percentage of participants |
| Placebo | 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) | Week 12 (n = 14, 14, 12) | 14.3 Percentage of participants |
| Placebo | 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) | Week 52 (n = 11, 14, 11) | 18.2 Percentage of participants |
| LCQ908 20mg | 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) | Week 24 (n = 13, 14, 12) | 35.7 Percentage of participants |
| LCQ908 20mg | 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) | Week 12 (n = 14, 14, 12) | 21.4 Percentage of participants |
| LCQ908 20mg | 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) | Week 52 (n = 11, 14, 11) | 21.4 Percentage of participants |
| LCQ908 40 mg | 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) | Week 12 (n = 14, 14, 12) | 50.0 Percentage of participants |
| LCQ908 40 mg | 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) | Week 52 (n = 11, 14, 11) | 27.3 Percentage of participants |
| LCQ908 40 mg | 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) | Week 24 (n = 13, 14, 12) | 33.3 Percentage of participants |
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.
Time frame: 12 weeks, 24 weeks, 52 weeks
Population: Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 24 (n = 13, 14, 12) | 30.8 Percentage of participants |
| Placebo | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 12 (n = 14, 14, 12) | 14.3 Percentage of participants |
| Placebo | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 52 (n = 11, 14, 11) | 18.2 Percentage of participants |
| LCQ908 20mg | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 24 (n = 13, 14, 12) | 14.3 Percentage of participants |
| LCQ908 20mg | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 12 (n = 14, 14, 12) | 14.3 Percentage of participants |
| LCQ908 20mg | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 52 (n = 11, 14, 11) | 14.3 Percentage of participants |
| LCQ908 40 mg | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 12 (n = 14, 14, 12) | 33.3 Percentage of participants |
| LCQ908 40 mg | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 52 (n = 11, 14, 11) | 18.2 Percentage of participants |
| LCQ908 40 mg | Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) | Week 24 (n = 13, 14, 12) | 16.7 Percentage of participants |
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
Time frame: 0-24 hours at Baseline, Week 12
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 | Triglycerides (Peak 0-24h) [n=12, 12, 11) | 56.9 Percent change |
| Placebo | Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 | Triglycerides (AUC 0-24h) [n=12, 12, 11) | 44.5 Percent change |
| LCQ908 20mg | Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 | Triglycerides (Peak 0-24h) [n=12, 12, 11) | 8.6 Percent change |
| LCQ908 20mg | Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 | Triglycerides (AUC 0-24h) [n=12, 12, 11) | 0.8 Percent change |
| LCQ908 40 mg | Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 | Triglycerides (Peak 0-24h) [n=12, 12, 11) | 6.3 Percent change |
| LCQ908 40 mg | Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 | Triglycerides (AUC 0-24h) [n=12, 12, 11) | 2.8 Percent change |
Secondary
Percent Change From Baseline in Fasting Triglycerides
Time frame: Baseline, 24 weeks, 52 weeks
Population: Full analysis set (FAS) consisted of all randomized patients, except for those who were mis-randomized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Triglycerides | Week 24 (n=13, 14, 12) | 4.9 Percent change |
| Placebo | Percent Change From Baseline in Fasting Triglycerides | Week 52 (n=11, 14, 11) | 15.2 Percent change |
| LCQ908 20mg | Percent Change From Baseline in Fasting Triglycerides | Week 24 (n=13, 14, 12) | -15.8 Percent change |
| LCQ908 20mg | Percent Change From Baseline in Fasting Triglycerides | Week 52 (n=11, 14, 11) | -6.7 Percent change |
| LCQ908 40 mg | Percent Change From Baseline in Fasting Triglycerides | Week 24 (n=13, 14, 12) | 5.5 Percent change |
| LCQ908 40 mg | Percent Change From Baseline in Fasting Triglycerides | Week 52 (n=11, 14, 11) | 4.9 Percent change |
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.
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour) | 11000 ng/mL *hr | Standard Deviation 4100 |
| LCQ908 20mg | Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour) | 14300 ng/mL *hr | Standard Deviation 7390 |
Secondary
Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg)
Average observed blood concentration measured by (AUC0-24)/24.
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg) | 459 ng/mL | Standard Deviation 171 |
| LCQ908 20mg | Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg) | 597 ng/mL | Standard Deviation 308 |
Secondary
Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours)
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours) | 6 hours |
| LCQ908 20mg | Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours) | 8 hours |
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.
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax) | Cmin | 312 ng/mL | Standard Deviation 120 |
| Placebo | Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax) | Cmax | 603 ng/mL | Standard Deviation 244 |
| LCQ908 20mg | Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax) | Cmin | 426 ng/mL | Standard Deviation 224 |
| LCQ908 20mg | Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax) | Cmax | 745 ng/mL | Standard Deviation 408 |