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ETC-1002

Phase 3

Hypercholesterolemia | Small molecule | Metabolic |Esperion Therapeutics, Inc.|Last Updated: Apr 4, 2023

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials6
Total Enrollment2,969
FDA Designations
No designations recorded
Clinical Trials (6)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02666664Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients With Hyperlipidemia and High CV Risk (CLEAR Harmony)PHASE3 COMPLETED 2,230Jan 21, 2016Mar 28, 2018May 11, 2020104 United States, Canada +4
NCT02178098Evaluation of ETC-1002 in Participants With Hypercholesterolemia and HypertensionPHASE2 COMPLETED 143Jun 16, 2014May 22, 2015Apr 4, 202343 United States
NCT02072161Evaluation of ETC-1002 vs Placebo in Patients Receiving Ongoing Statin TherapyPHASE2 COMPLETED 133Mar 1, 2014Jan 1, 2015Mar 29, 201940 United States
NCT01941836Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic PatientsPHASE2 COMPLETED 349Sep 1, 2013Nov 1, 2014Mar 29, 201968 United States
NCT01779453A Study of the Safety, Pharmacokinetic Drug Interaction and Efficacy of ETC-1002 and Atorvastatin in Subjects With HypercholesterolemiaPHASE2 COMPLETED 58Dec 1, 2012Aug 1, 2013Mar 29, 20193 United States
NCT01751984A Study of the Efficacy and Safety of ETC-1002 in Participants With Statin IntolerancePHASE2 COMPLETED 56Oct 4, 2012May 1, 2013Apr 4, 20225 United States
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Study Endpoints
Primary Endpoints
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Up to approximately 52 weeks

TEAEs, defined as adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported.

Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event
Up to approximately 52 weeks

TEAEs, defined as AEs that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. Cardiovascular events were considered as adverse events of special interest. Treatment-emergent = TE.

Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations
Up to approximately 52 weeks

TEAEs of special interest (AESIs) were predefined and monitored throughout the study. Creatine kinase elevations were assessed using the following preferred term: Blood creatine phosphokinase increased (system organ class: investigations).

Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders
Up to approximately 52 weeks

Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to hepatic events were assessed using the following preferred terms and laboratory abnormalities: aspartate aminotransferase (AST) increased, Alanine aminotransferase (ALT) increased, Hepatic enzyme increased, Blood bilirubin increased, liver function test (LFT) abnormal, LFT increased, hepatic enzyme abnormal, transaminases increased, potential Hy's Law cases (PHLC) \[AST and (\&)/or ALT \>3 x upper limit of normal (ULN) with concurrent total bilirubin \>2 x ULN\], AST and/or ALT \>3 x ULN, and total bilirubin \>2 x ULN (system organ class: investigations). AST and ALT values were repeated and confirmed. "Repeated and confirmed" was defined as a participant having the last on-study LFT \> x ULN, the last on-treatment LFT \> x ULN, or LFT \> x ULN followed by another LFT \> x ULN.

Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia
Up to approximately 52 weeks

Treatment-emergent AESIs were predefined and monitored throughout the study. Hypoglycemia was assessed using the following preferred terms: hypoglycaemia (system organ class: metabolism and nutrition disorders); blood glucose abnormal and blood glucose decreased (system organ class: investigations). The percentage of unique participants is reported in the "Overall hypoglycemia AESIs" category; a participant could have been represented in more than one of the individual hypoglycemia AESIs.

Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis
Up to approximately 52 weeks

Treatment-emergent AESIs were predefined and monitored throughout the study. Metabolic acidosis was assessed using the preferred term metabolic acidosis (system organ class: metabolism and nutrition disorders).

Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder
Up to approximately 52 weeks

Treatment-emergent AESIs were predefined and monitored throughout the study. Muscular safety was assessed using the following preferred terms and laboratory abnormalities: myalgia, muscle spasms, pain in extremity, muscular weakness (system organ class: musculoskeletal and connective tissue disorders), and creatine kinase \>5 ULN (repeated and confirmed). The percentage of unique participants is reported in the "Overall muscular disorder AESIs" category; a participant could have been represented in more than one of the individual muscular disorder AESIs.

Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder
Up to approximately 52 weeks

Treatment-emergent AESIs were predefined and monitored throughout the study. Neurocognitive disorder was assessed using the following preferred terms: memory impairment, amnesia, and cognitive disorder (system organ class: nervous system disorders); confusional state and disorientation (system organ class: psychiatric disorders). The percentage of unique participants is reported in the "Overall neurocognitive disorder AESIs" category; a participant could have been represented in more than one of the individual neurocognitive disorder AESIs.

Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus
Up to approximately 52 weeks

Treatment-emergent AESIs were predefined and monitored throughout the study. New onset or worsening diabetes was assessed using the following preferred terms: type 2 diabetes mellitus, diabetes mellitus, hyperglycaemia, glucose tolerance impaired, diabetes mellitus inadequate control, and impaired fasting glucose (system organ class: metabolism and nutrition disorders); blood glucose increased, glycosylated haemoglobin increased, blood glucose abnormal, and glucose urine present (system organ class: investigations); and glycosuria (system organ class: renal and urinary disorders). The percentage of unique participants is reported in the "Overall new onset/worsening diabetes mellitus AESIs" category; a participant could have been represented in more than one of the individual new onset/worsening diabetes mellitus AESIs.

Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder
Up to approximately 52 weeks

Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to renal events were assessed using the following preferred terms: renal failure, renal impairment, acute kidney injury (system organ class: renal and urinary disorders); blood creatinine increased, glomerular filtration rate decreased, blood urea increased, estimated glomerular filtration rate (eGFR) \<30 milliliter per minute per 1.73 square meter (ml/min/1.73m\^2), and change from baseline in creatinine \>1 mg/dL (system organ class: investigations); and gout (system organ class: metabolism and nutrition disorders). The percentage of unique participants is reported in the "Overall renal disorder AESIs" category; a participant could have been represented in more than one of the individual renal disorder AESIs.

Change From Baseline to Week 52 in Uric Acid (Urate) Level
Baseline and Week 52

Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels.

Change From Baseline to Week 52 in Creatinine Level
Baseline and Week 52

Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels.

Change From Baseline to Week 52 in Hemoglobin Level
Baseline and Week 52

Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels.

Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6
Baseline; 6 weeks

Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week -1 and Week 0. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. For the Week 6 endpoint, missing values at Week 6 were imputed using the last observation carried forward (LOCF) procedure, with only post-Baseline values carried forward. Modified Intent-to-Treat (mITT) Population is defined as all randomized participants who received at least 1 dose of study drug, had a Baseline assessment, and had at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of study drug

Percent change from baseline in calculated low density lipoprotein-cholesterol (LDL-C)
12 weeks
Percent change in calculated low density lipoprotein-cholesterol (LDL-C)
Baseline and 12 weeks
Area under the plasma concentration versus time curve (AUC) of atorvastatin and its active metabolites
4 and 8 weeks
Peak plasma concentration (Cmax) of atorvastatin and its active metabolites
4 and 8 weeks
Number of subjects with adverse events, clinical lab abnormalities and other safety findings
8 weeks
Percent Change From Baseline to Week 8 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C)
Baseline; 8 weeks

Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. Least square (LS) mean percent change from Baseline to Week 8 was based on an analysis of covariance (ANCOVA) model with effects of treatment and Baseline value as a covariate. Missing LDL-C values at Week 8 were imputed using the last observation carried forward (LOCF) procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.

Secondary Endpoints
Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
Baseline; Week 12
Absolute Change From Baseline to Week 12 in LDL-C
Baseline; Week 12
Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6
Baseline; 6 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
ETC-1002EXPERIMENTALETC-1002 180 mg/day
PlaceboPLACEBO_COMPARATORPlacebo control
ETC-1002 120 mg/dayEXPERIMENTALOrally, once daily in morning as capsules
ETC-1002 180 mg/dayEXPERIMENTALOrally, once daily in morning as capsules
ezetimibe 10mg/dayACTIVE_COMPARATOROrally, once daily in morning as capsules
ETC-1002 120 mg/day + ezetimibe 10mg/dayEXPERIMENTALOrally, once daily in morning
ETC-1002 180 mg/day + ezetimibe 10mg/dayEXPERIMENTALOrally, once daily in morning
Interventions
NameTypeDescription
ETC-1002DRUGETC-1002 180 mg tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)
PlaceboDRUGMatching placebo tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)
Statin TherapyDRUGPatients remained on ongoing statin therapy (not study provided) of either Atorvastatin 10mg or 20mg; Simvastatin 5mg, 10mg or 20mg; Rosuvastatin 5mg or 10mg; or Pravastatin 10mg, 20mg or 40mg.
EzetimibeDRUGPatients receive ezetimibe
AtorvastatinDRUGAtorvastatin 10mg once daily for 8 weeks
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites104

Inclusion Criteria: * Fasting LDL-C ≥ 70 mg/dL * High cardiovascular risk (diagnosis of HeFH or ASCVD) * Be on maximally tolerated lipid-modifying therapy Exclusion Criteria: * Total fasting triglyceride ≥500 mg/dL * Renal dysfunction or nephrotic syndrome or history of nephritis * Body Mass Inde...

Countries:United StatesCanadaGermanyNetherlandsPolandUnited Kingdom
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