| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02666664 | Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients With Hyperlipidemia and High CV Risk (CLEAR Harmony) | PHASE3 | COMPLETED | 2,230 | — | — | Jan 21, 2016 | Mar 28, 2018 | May 11, 2020 | 104 | United States, Canada +4 |
| NCT02178098 | Evaluation of ETC-1002 in Participants With Hypercholesterolemia and Hypertension | PHASE2 | COMPLETED | 143 | — | — | Jun 16, 2014 | May 22, 2015 | Apr 4, 2023 | 43 | United States |
| NCT02072161 | Evaluation of ETC-1002 vs Placebo in Patients Receiving Ongoing Statin Therapy | PHASE2 | COMPLETED | 133 | — | — | Mar 1, 2014 | Jan 1, 2015 | Mar 29, 2019 | 40 | United States |
| NCT01941836 | Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients | PHASE2 | COMPLETED | 349 | — | — | Sep 1, 2013 | Nov 1, 2014 | Mar 29, 2019 | 68 | United States |
| NCT01779453 | A Study of the Safety, Pharmacokinetic Drug Interaction and Efficacy of ETC-1002 and Atorvastatin in Subjects With Hypercholesterolemia | PHASE2 | COMPLETED | 58 | — | — | Dec 1, 2012 | Aug 1, 2013 | Mar 29, 2019 | 3 | United States |
| NCT01751984 | A Study of the Efficacy and Safety of ETC-1002 in Participants With Statin Intolerance | PHASE2 | COMPLETED | 56 | — | — | Oct 4, 2012 | May 1, 2013 | Apr 4, 2022 | 5 | United States |
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.
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.
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).
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.
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.
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).
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.
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.
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.
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.
Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels.
Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels.
Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels.
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 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.
| Arm | Type | Description |
|---|---|---|
| ETC-1002 | EXPERIMENTAL | ETC-1002 180 mg/day |
| Placebo | PLACEBO_COMPARATOR | Placebo control |
| ETC-1002 120 mg/day | EXPERIMENTAL | Orally, once daily in morning as capsules |
| ETC-1002 180 mg/day | EXPERIMENTAL | Orally, once daily in morning as capsules |
| ezetimibe 10mg/day | ACTIVE_COMPARATOR | Orally, once daily in morning as capsules |
| ETC-1002 120 mg/day + ezetimibe 10mg/day | EXPERIMENTAL | Orally, once daily in morning |
| ETC-1002 180 mg/day + ezetimibe 10mg/day | EXPERIMENTAL | Orally, once daily in morning |
| Name | Type | Description |
|---|---|---|
| ETC-1002 | DRUG | ETC-1002 180 mg tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided) |
| Placebo | DRUG | Matching placebo tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided) |
| Statin Therapy | DRUG | Patients 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. |
| Ezetimibe | DRUG | Patients receive ezetimibe |
| Atorvastatin | DRUG | Atorvastatin 10mg once daily for 8 weeks |
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...