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LCQ908

Phase 3

Familial Chylomicronemia Syndrome (FCS) | Small molecule | Metabolic |Novartis AG|Last Updated: Dec 19, 2020

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment45

FDA Designations

No designations recorded

Clinical trial landscape

LCQ908 · 6 trials · 6 indications

Phase 3 1Phase 2 2Phase 1 3
NCT01514461A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia SyndromeFamilial Chylomicronemia Syndrome (FCS)
COMPLETED45 Analytics
PHASE3COMPLETED
A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
Familial Chylomicronemia Syndrome (FCS)Unlock trial analytics

Study Endpoints

Primary Endpoints

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.

Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24
From baseline to week 24

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

Change from baseline in triglycerides (TG) relative to placebo at 6 weeks
Baseline, 6 weeks

The dose response signal of 3 dose regiments of LCQ908 in patients at risk for non-FCS chylomicronemia as was measured by change from baseline in triglycerides (TG) relative to placebo at 6 weeks.

Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908
Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing
Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908
Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing
Maximum plasma concentration (Cmax) of LCQ908
Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908 for part I of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 for part I of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

Maximum plasma concentration of LCQ908 (Cmax) for Part I of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part I of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908 for Part II of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 for Part II of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

Maximum plasma concentration of LCQ908 (Cmax) for Part II of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part II of the study
Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing

This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

Fasting and postprandial plasma triglycerides
baseline and 3 weeks after initiation of each dose level (a test meal will be served at baseline and on Day 21 of treatment)

Secondary Endpoints

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 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 of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline
Baseline, 12 weeks, 24 weeks, 52 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
LCQ908 20 mgEXPERIMENTALIn 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.
LCQ908 40 mgEXPERIMENTALIn 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.
PlaceboPLACEBO_COMPARATORIn 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.
pradigastat (LCQ908) 5mg/10mgEXPERIMENTALPatients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
pradigastat (LCQ908) 10mg/20mgEXPERIMENTALPatients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
LCQ908 1EXPERIMENTALLCQ908 (Diacylglycerol acyltransferase inhibitor)once daily for 12 weeks
LCQ908 2EXPERIMENTALLCQ908 once daily for 12 weeks
LCQ908 3EXPERIMENTALLCQ908 once daily for 12 weeks
FenofibrateACTIVE_COMPARATORIntervention Type: Drug Intervention Name: Fenofibrate
Fish OilACTIVE_COMPARATORFish oil once daily for 12 weeks
Arm Label: PlaceboPLACEBO_COMPARATORIntervention Type: other Intervention Name: other
LCQ908 (mild renal impairment plus healthy volunteers)EXPERIMENTALHealthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with mild renal impairment and will receive a single 40 mg dose of LCQ908.
LCQ908 (moderate renal impairment plus healthy volunteers)EXPERIMENTALHealthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with moderate renal impairment and will receive a single 40 mg dose of LCQ908.
LCQ908 (severe renal impairment plus healthy volunteers)EXPERIMENTALHealthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with severe renal impairment and will receive a single 40 mg dose of LCQ908.
LCQ908 (mild hepatic impairment plus healthy volunteers)EXPERIMENTALHealthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with mild hepatic impairment and will receive a single dose of LCQ908.
LCQ908 (moderate hepatic impairment plus healthy volunteers)EXPERIMENTALHealthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with moderate hepatic impairment and will receive a single dose of LCQ908.
LCQ908 (severe hepatic impairment plus healthy volunteers)EXPERIMENTALHealthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with severe hepatic impairment and will receive a single dose of LCQ908.
LCQ908EXPERIMENTAL -

Interventions

NameTypeDescription
LCQ908DRUGLCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
PlaceboDRUGLCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
FenofibrateDRUGFenofibrate once daily 12 weeks
Fish OilDRUGFish Oil once daily for 12 weeks
Placebo of LCQ908DRUGMatching placebo of LCQ908
Placebo of fenofibrateDRUGMatching placebo of fenofibrate
Placebo of fish oilDRUGMatching placebo of fish oil capsule
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites14

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 ult...

Countries:United StatesCanadaFranceGermanyNetherlandsSouth AfricaSpainUnited KingdomRussia
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Frequently asked questions about LCQ908

What is LCQ908 used for?

LCQ908 is an investigational small molecule being developed for metabolic conditions, including Familial Chylomicronemia Syndrome (FCS), hyperlipoproteinemia, renal impairment, hepatic impairment, Non-Familial Chylomicronemia Syndrome (Non-FCS), and Non-alcoholic Fatty Liver Disease (NAFLD). It is in Phase 3 development for these indications.

Who makes LCQ908?

LCQ908 is being developed by Novartis AG, a multinational pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. The drug is currently in Phase 3 clinical development for metabolic indications.

What phase is LCQ908 in?

LCQ908 is in Phase 3 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. Clinical trials have been completed for earlier phases, and the drug is being studied for conditions such as Familial Chylomicronemia Syndrome and hyperlipoproteinemia.

What clinical trials has LCQ908 been in?

LCQ908 has been studied in several completed trials. NCT01146522 assessed safety and pharmacokinetics in patients with severe hypertriglyceridemia. NCT01558323 and NCT01594957 evaluated pharmacokinetics in renal and hepatic impairment, respectively. NCT01594983 was a pilot efficacy and safety study in Non-Familial Chylomicronemia Syndrome.

Is LCQ908 the same as pradigastat?

LCQ908 is also known as pradigastat. It is an investigational small molecule being developed by Novartis for metabolic conditions. The drug has been studied in clinical trials for hypertriglyceridemia and related disorders.