Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication ZETIA ® is indicated: In combination with a statin, or alone when additional low-density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). FDA label
Also known as ezetimibe, Zetia, SCH 58235, Crestor
Ezetimibe+ Rosuvastatin · 29 trials · 11 indications
Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The change from baseline was calculated. Results were reported as a M-estimate.
An AE was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized
An AE was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that had study drug discontinued due to an AE was summarized.
Gastrointestinal-related AEs included all preferred terms within system organ class of Gastrointestinal Disorders except Chapped Lips and Toothache.
Gallbladder-related AEs included Bile Duct Obstruction, Bile Duct Stone, Bile Duct Stenosis, Biliary Colic, Cholangitis, Cholecystectomy, Cholecystitis, Cholelithiasis, Gallbladder Disorder, Gallbladder Perforation, Hepatic Pain, and Hydrocholecystis.
Allergic Reaction or Rash AEs included Allergy to Arthropod Sting, Anaphylactoid Reaction, Anaphylactic Reaction, Anaphylatic Shock, Anaphylactoid Shock, Angioedema, Conjunctivitis Allergic, Contrast Media Reaction, Dermatitis, Dermatitis Allergic, Dermatitis Atopic, Dermatitis Bullous, Dermatitis Contact, Dermatitis Psoriasiform, Drug Hypersensitivity, Eczema, Eosinophila, Erythema, Eye Allergy, Face Oedema, Hypersensitivity, Mechanical Urticaria, Palmar Erythema, Periorbital Oedema, Photodermatosis, Photosensitivity Allergic reaction, Photosensitivity Reaction, Pigmentation Disorder, Pruritus, Pruritus Generalised, Rash, Rash Erythematous, Rash Follicular, Rash Generalised, Rash Maculo-Papular, Rash Papulosquamous, Rash Pruritic, Rash Pustular, Rash Vesicular, Rhinitis, Rhinitis Allergic, Rosacea, Skin Exfoliation, Skin Disorder, Skin Hyperpigmentation, Skin Lesion, Skin Mass, Skin Ulcer, Subcutaneous Nodule, Swelling Face, Systemic Lupus Erythematosus Rash, Urticaria.
Hepatitis-related AEs included Cholestasis, Cytolytic Hepatitis, Hepatic Cyst, Hepatic Failure, Hepatic Lesion, Hepatic Necrosis, Hepatitis, Hepatitis Cholestatic, Hepatitis Fulminant, Hepatitis Infectious, Hepatocellular Injury, Hepatomegaly, Jaundice, Jaundice Cholestatic.
Participants had ALT levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of ALT that were 3 x ULN or greater were recorded. The ALT ULN was 40 U/L.
Participants had AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of AST that were 3 x ULN or greater were recorded. The AST ULN was 40 U/L..
Participants had ALT and AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 3 x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Participants had ALT levels assessed throughout the 12 week treatment period. Participants who had an assessments of ALT that was 5x ULN or greater were recorded. The ALT ULN was 40 U/L.
Participants had AST levels assessed throughout the 12 week treatment period. Participants who had an assessments of AST that was 5x ULN or greater were recorded. The AST ULN was 40 U/L.
Participants had ALT levels assessed throughout the 12 week treatment period. Participants who had an assessments of ALT that was 10x ULN or greater were recorded. The ALT ULN was 40 U/L.
Participants had AST levels assessed throughout the 12 week treatment period. Participants who had an assessments of AST that was 10x ULN or greater were recorded. The AST ULN was 40 U/L.
Participants had ALT and AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 10x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Percentage of Participants with Potential Hy's Law Condition (defined as serum ALT or serum AST elevations \>3xULN, with serum alkalinephosphatase \<2xULN and total bilirubin (TBL) ≥2xULN) was summarized. The ALT and AST ULNs were 40 U/L. The ULN for alkaline phosphatase was 359 IU/L and the ULN for total bilirubin was 1.2 mg/dL.
Participants had creatine phosphokinase (CK) levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days that were reported as at least possibly-related to study drug were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who had study drug discontinued due to an AE was summarized.
Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The change from baseline was calculated.
Gastrointestinal-related AEs included all preferred terms within system organ class of Gastrointestinal Disorders except Chapped Lips and Toothache.
Participants had ALT levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of ALT that were 3 x ULN or greater were recorded. The ALT ULN was 40 U/L.
Participants had AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of AST that were 3 x ULN or greater were recorded. The AST ULN was 40 U/L.
Participants had ALT and AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 3 x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Participants had ALT levels assessed throughout the 12 week treatment period. Participants who had an assessment of ALT that was 5x ULN or greater were recorded. The ALT ULN was 40 U/L.
Participants had AST levels assessed throughout the 12 week treatment period. Participants who had an assessment of AST that was 5x ULN or greater were recorded. AST ULN was 40 U/L.
Participants had ALT and AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 5 x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Participants had ALT levels assessed throughout the 12 week treatment period. Participants who had an assessment of ALT that was 10x ULN or greater were recorded. The ALT ULN was 40 U/L.
Participants had AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of AST that were 10x ULN or greater were recorded. The AST ULN was 40 U/L.
Participants had ALT and AST levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 10x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Participants had creatine phosphokinase (CK) levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Participants had CK levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Participants had CK levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days that were reported as at least possibly-related to study drug were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
LDL-C levels measured at Baseline and after 6 weeks of treatment (Week 6; end of Phase I). Baseline was defined as the average value of the measurements taken at Visits 3 and 4. LDL-C was calculated using the Friedewald method when triglyceride (TG)\<350 mg/dL (3.95 mmol/L) and beta quantification ultracentrifugation when TG≥350 mg/dL (3.95 mmol/L).
Serum LDL-C levels calculated at baseline and after 12 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) - (High-density lipoprotein cholesterol \[HDL-C\] + triglyceride \[TG\]/5).
An adverse event is any unfavorable medical event occurring in a subject to whom an investigational product is administered, and a causal relationship between the administered investigational product and an adverse event is not always clarified. That is, an adverse event is any unfavorable or unintended sign (including an abnormal change in laboratory test values), symptom, or disease, and a causal relationship to the relevant investigational product is not considered. Any adverse event that was considered treatment-related was considered an adverse reaction.
Ezetimibe/simvastatin co-administered with niacin extended release compared to niacin extended release monotherapy on the percent change, from baseline in LDL-C after 24 weeks - 24 Week Measure Minus Baseline
On each of 2 days prior to the last day of each treatment period, participants consumed 2 large eggs in the evening. On the morning of the final day of each treatment period, fasting participants were given a site-prepared, cholesterol-enriched milkshake that provided 1114 calories of total energy (\~44% of calories from fat, \~40% of calories from carbohydrate and \~17% of calories from protein) and 504 mg of cholesterol. The milkshake was consumed over a 15-minute period. Plasma samples were collected immediately prior to consumption of the test meal (baseline) and at 2, 3, 4, and 6 hours afterwards for isolation and analysis of lipoprotein fractions. The geometric mean concentration level was calculated using data obtained at all timepoints.
The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular death, major coronary Event (non-fatal myocardial infarction \[MI\], documented unstable angina \[UA\] requiring hospitalization, or coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) ≥ 30 days after randomization), or non-fatal Stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced cardiovascular death, major coronary event, or non-fatal stroke within 7 years from randomization.
Least squares mean percent change from Baseline in LDL-C at the end of Step 1 (Week 6) in the pooled groups who received ezetimibe plus simvastatin compared with pooled groups who received simvastatin monotherapy
Plasma LDL-C determined following a standard ultracentrifugation / precipitation (quantification) procedure (direct LDL-C). Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
| Arm | Type | Description |
|---|---|---|
| Ezetimibe 10 mg | ACTIVE_COMPARATOR | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin placebo capsules once daily for 12 weeks |
| Rosuvastatin 2.5 mg | ACTIVE_COMPARATOR | 1 Rosuvastatin 2.5 mg capsule, 1 Rosuvastatin placebo capsule and 1 Ezetimibe placebo tablet once daily for 12 weeks. |
| Rosuvastatin 5.0 mg | ACTIVE_COMPARATOR | 2 Rosuvastatin 2.5 mg capsules and Ezetimibe placebo tablet once daily for 12 weeks. |
| Ezetimibe 10 mg+ Rosuvastatin 2.5 mg | EXPERIMENTAL | 1 Ezetimbie 10 mg tablet, 1 Rosuvastatin 2.5 mg capsule and 1 Rosuvastatin placebo capsule once daily for 12 weeks. |
| Ezetimibe 10 mg+ Rosuvastatin 5.0 mg | EXPERIMENTAL | 1 Ezetimbie 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules once daily for 12 weeks. |
| Ezetimibe 10 mg + Rosuvastatin 2.5 mg | EXPERIMENTAL | 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein- cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may be increased to 5.0 mg |
| Ezetimibe 10 mg + Rosuvastatin 5.0 mg | EXPERIMENTAL | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. |
| Atorvastatin 10 mg | ACTIVE_COMPARATOR | 1 atorvastatin 10 mg capsule, 1 ezetimide 10 mg placebo tablet, and 1 atorvastatin 10 mg placebo capsule orally once daily for 12 weeks. |
| Atorvastatin 20 mg | ACTIVE_COMPARATOR | 2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks. |
| Ezetimibe 10 mg + Atorvastatin 10 mg | EXPERIMENTAL | 1 Ezetimibe 10 mg tablet, 1 atorvastatin 10 mg capsule and 1 atorvastatin 10 mg placebo capsule orally, once daily for 12 weeks |
| Ezetimibe 10 mg + Atorvastatin 20 mg | EXPERIMENTAL | 1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks |
| Phase I: ezetimibe (EZ) 10 mg + atorvastatin (Atorva) 10 mg | EXPERIMENTAL | Co-administration of EZ 10 mg tablet + Atorva 10 mg tablet; once daily for 6 weeks |
| Phase I: Atorvastatin 20 mg | ACTIVE_COMPARATOR | Atorvastatin 20 mg tablet once daily for 6 weeks |
| Phase I: Rosuvastatin 10 mg | ACTIVE_COMPARATOR | Rosuvastatin 10 mg tablet once daily for 6 weeks |
| Phase II: EZ 10mg+Atorva 10mg | EXPERIMENTAL | Participants who had previously received EZ 10 mg + Atorva 10 mg in Phase I and continued on EZ 10 mg + Atorva 10 mg once daily for 6 weeks during Phase II regardless of whether or not LDL-C goals were achieved in Phase I |
| Phase II: EZ 10mg + Atorva 20mg [A] | EXPERIMENTAL | Participants who had previously received Atorva 20 mg in Phase I and did not reach LDL-C goal and were switched to EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II |
| Phase II: Atorva 40mg | ACTIVE_COMPARATOR | Participants who had previously received Atorva 20 mg in Phase I and did not reach LDL-C goal and were switched Atorva 40 mg once daily for 6 weeks in Phase II |
| Phase II: EZ 10mg + Atorva 20mg [R] | EXPERIMENTAL | Participants who had previously received Rosuvastatin 10 mg in Phase I and did not reach LDL-C goal and received EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II |
| Phase II: Rosuvastatin 20mg | ACTIVE_COMPARATOR | Participants who had previously received Rosuvastatin 10 mg in Phase I and did not reach LDL-C goal and were switched to Rosuvastatin 20 mg once daily for 6 weeks in Phase |
| Ezetimibe | EXPERIMENTAL | Ezetimibe 10-mg tablet once daily for 12 weeks |
| Placebo | PLACEBO_COMPARATOR | Placebo to match ezetimibe 10-mg tablet once daily for 12 weeks |
| ezetimibe/simvastatin 10/40 | EXPERIMENTAL | Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, ezetimibe/simvastatin 10/40 was administered once daily in tablet form during the 6-week double-blind treatment period |
| atorvastatin 40 mg | ACTIVE_COMPARATOR | Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, 40 mg atorvastatin was administered once daily in tablet form during the 6-week double-blind treatment period |
| Ezetimibe + Atorvastatin | EXPERIMENTAL | Ezetimibe 10 mg + Atorvastatin 20 mg |
| Ezetimibe + Simvastatin | EXPERIMENTAL | Ezetimibe 10 mg + Simvastatin 20 mg |
| 1 | ACTIVE_COMPARATOR | - |
| 2 | ACTIVE_COMPARATOR | - |
| Vytorin 10/10 | EXPERIMENTAL | Ezetimibe 10 mg with Simvastatin 10 mg |
| Vytorin 10/20 | EXPERIMENTAL | Ezetimibe 10 mg with Simvastatin 20 mg |
| Vytorin 10/40 | EXPERIMENTAL | Ezetimibe 10 mg with Simvastatin 40 mg |
| Part 1 - Arm 1 | ACTIVE_COMPARATOR | ezetimibe/simvastatin combination tablet + niacin (ER) |
| Part 1 -Arm 2 | ACTIVE_COMPARATOR | ezetimibe/simvastatin |
| Part 1 - Arm 3 | ACTIVE_COMPARATOR | Niacin (ER) |
| Part 2 - Arm 1 | ACTIVE_COMPARATOR | ezetimibe/simvastatin combination tablet + niacin (ER) |
| Part 2 - Arm 2 | PLACEBO_COMPARATOR | ezetimibe/simvastatin combination tablet + niacin (Pbo) |
| Ezetimibe→Placebo | EXPERIMENTAL | After a 2-week single- blind placebo run-in, participants will receive ezetimibe 10 mg once daily for 4 weeks and then receive placebo once daily for 4 weeks. |
| Placebo→ Ezetimibe | EXPERIMENTAL | After a 2-week single- blind placebo run-in, participants will receive placebo once daily for 4 weeks and then receive ezetimibe10 mg once daily for 4 weeks. |
| ezetimibe/simvastatin | EXPERIMENTAL | One Ezetimibe 10 mg/simvastatin 40 mg combination tablet and two simvastatin 40 mg placebo tablets once per day. |
| simvastatin | ACTIVE_COMPARATOR | One simvastatin 40 mg tablet, one ezetimibe/simvastatin combination 10/40 placebo tablet and one simvastatin 40 mg placebo tablet once per day. |
| Pooled subjects who received ezetimibe with simvastatin | EXPERIMENTAL | Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg |
| Pooled subjects who received simvastatin monotherapy | ACTIVE_COMPARATOR | Pooled subjects who received ezetimibe matching placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg |
| Ezetimibe 10 mg + Simvastatin Placebo + Simvastatin 20 mg | EXPERIMENTAL | Participants were instructed to take one 10-mg ezetimibe tablet and one simvastatin placebo tablet orally in the evening every day for six weeks in addition to their daily, oral, open-label, 20-mg simvastatin tablet. |
| Ezetimibe Placebo + Simvastatin 40 mg | ACTIVE_COMPARATOR | Participants were instructed to take one ezetimibe placebo tablet and one simvastatin 20-mg tablet orally in the evening every day for six weeks in addition to their daily, oral, open-label, 20-mg simvastatin tablet. |
| 3 | ACTIVE_COMPARATOR | simvastatin 20 mg tablet |
| 4 | PLACEBO_COMPARATOR | matching placebo |
| Atorvastatin | ACTIVE_COMPARATOR | - |
| EZ/Simva | EXPERIMENTAL | - |
| Placebo/Simva | PLACEBO_COMPARATOR | - |
| Placebo + Atorvastatin | PLACEBO_COMPARATOR | Participants who received placebo in the parent study (P00692) receive placebo (blinded) + atorvastatin (10 mg/day; open-label) in this study. |
| Ezetimibe: Base Study | EXPERIMENTAL | 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks. |
| Placebo: Base Study | PLACEBO_COMPARATOR | Placebo for ezetimibe 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks. |
| Ezetimibe: Extension | EXPERIMENTAL | 10-mg tablet, oral taken once daily concomitantly with simvastatin for 48 weeks. |
| Placebo: Extension | PLACEBO_COMPARATOR | Placebo for ezetimibe tablet, oral taken once daily concomitantly with simvastatin for 48 weeks. |
| Ezetimibe+Atorvastatin | EXPERIMENTAL | Participants receive ezetimibe 10 mg via oral tablet once daily co-administered with atorvastatin 40 mg (starting dose) via oral tablet once daily in the morning (may be titrated up to a maximum daily dose of 80 mg for atorvastatin, if needed) for up to 24 months. |
| Ezetimibe+Simvastatin | EXPERIMENTAL | Participants receive ezetimibe 10 mg via oral tablet once daily co-administered with simvastatin 40 mg (starting dose) via oral tablet once daily in the evening (may be titrated up to a maximum daily dose of 80 mg for simvastatin, if needed) for up to 24 months. |
| Ezetimibe 10 mg + Atorvastatin | EXPERIMENTAL | Ezetimibe 10 mg plus atorvastatin 10 to 80 mg daily for up to 12 months |
| Ezetimibe 10 mg + Atorvastatin 40 mg | EXPERIMENTAL | Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks. |
| Atorvastatin 80 mg | ACTIVE_COMPARATOR | Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks. |
| Ezetimibe 10 mg + Atorvastatin 80 mg | EXPERIMENTAL | Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks. |
| Ezetimibe 10mg and Atorvastatin 10mg | ACTIVE_COMPARATOR | Ezetimibe 10mg tablet and Atorvastatin 10mg tablet coadministered |
| 10mg Ezetimibe/10mg Atorvastatin | EXPERIMENTAL | 10mg Ezetimibe/10mg atorvastatin combination tablet |
| Ezetimibe 10mg and Atorvastatin 80mg | ACTIVE_COMPARATOR | Ezetimibe 10mg tablet and Atorvastatin 80mg tablet coadministered |
| 10mg Ezetimibe/80mg Atorvastatin | EXPERIMENTAL | Ezetimibe/atorvastatin 10mg/80mg combination tablet |
| Group A | ACTIVE_COMPARATOR | SCH 58235 (Period 1) Pitavastatin (Period 2) Coadministration (Period 3) |
| Group B | ACTIVE_COMPARATOR | SCH 58235 (Period 1) Coadministration (Period 2) Pitavastatin (Period 3) |
| Group C | ACTIVE_COMPARATOR | Pitavastatin (Period 1) SCH 58235 (Period 2) Coadministration (Period 3) |
| Group D | ACTIVE_COMPARATOR | Pitavastatin (Period 1) Coadministration (Period 2) SCH 58235 (Period 3) |
| Group E | ACTIVE_COMPARATOR | Coadministration (Period 1) SCH 58235 (Period 2) Pitavastatin (Period 3) |
| Group F | ACTIVE_COMPARATOR | Coadministration (Period 1) Pitavastatin (Period 2) SCH 58235 (Period 3) |
| Treatment A | ACTIVE_COMPARATOR | Treatment A: subjects will be given a single oral dose of cyclosporine 100 mg capsules on Day 1. |
| Treatment B | ACTIVE_COMPARATOR | Treatment B: subjects will receive single oral daily doses of ezetimibe 20 mg (2 x 10 mg tablets) on Days 1 through 6, followed by coadministration of a single oral dose of ezetimibe 20 mg (2 x 10 mg tablets) and cyclosporine 100 mg capsule on Day 7. |
| Ezetimibe + Rosuvastatin | EXPERIMENTAL | - |
| Rosuvastatin | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Ezetimibe 10 mg | DRUG | - |
| Rosuvastatin 2.5 mg | DRUG | - |
| Placebo for Ezetimibe | DRUG | - |
| Placebo for Rosuvastatin | DRUG | - |
| Ezetimibe | DRUG | - |
| Rosuvastatin | DRUG | - |
| Atorvastatin 10 mg | DRUG | - |
| Placebo for Ezetimibe 10 mg tablet | DRUG | - |
| Placebo for Atorvastatin 10 mg capsule | DRUG | - |
| Diet control/Daily Exercise | BEHAVIORAL | Diet and Daily exercise program as per Japan Atherosclerosis Society Guideline 2012 (JAS2012) |
| atorvastatin | DRUG | - |
| Comparator: rosuvastatin | DRUG | - |
| Placebo | DRUG | oral tablets: placebo to match ezetimibe 10 mg; administered once daily during the 5-week, single-blind, placebo run-in and diet stabilization period and 12-week double-blind treatment period |
| ezetimibe/simvastatin 10/40 | DRUG | ezetimibe/simvastatin 10/40 tablet once daily for 6 weeks. |
| atorvastatin 40 mg | DRUG | atorvastatin 40 mg tablet once daily for 6 weeks |
| atorvastatin 20 mg | DRUG | All participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization |
| Simvastatin | DRUG | Simvastatin 20 mg daily |
| ezetimibe and atorvastatin | DRUG | ezetimibe 10 mg and atorvastatin 10 mg daily for 12 weeks |
| Placebo (unspecified) | DRUG | Placebo (unspecified) daily for 12 weeks |
| ezetimibe with simvastatin | DRUG | Ezetimibe 10 mg with Simvastatin 10 mg once daily for a total of eight weeks |
| Comparator: ezetimibe/simvastatin + niacin (ER) | DRUG | ezetimibe/simvastatin 10/20mg tablet + niacin (ER) tablet, titrating to 2g, po qd. Treatment time will be \~24 weeks |
| Comparator: Placebo to ezetimibe/simvastatin | DRUG | ezetimibe/simvastatin (Pbo) tablet. Treatment time will be \~24 weeks. |
| Comparator: niacin (ER) tablet | DRUG | niacin (ER) tablet, titrating to 2g, po qd. Treatment time will be \~24 weeks |
| Comparator: ezetimibe (+) simvastatin | DRUG | ezetimibe/simvastatin 10/20mg tablet. Treatment time will be \~24 weeks. |
| Comparator: Placebo to Niacin (ER) | DRUG | Niacin (ER) (Pbo) tablet. Treatment time will be \~24 weeks. |
| Comparator: ezetimibe/simvastatin and niacin (ER) | DRUG | ezetimibe/simvastatin 10/20mg tablet + niacin (ER) tablet 2g, po qd. Treatment time will be \~40 additional weeks for a total of 64 weeks |
| Comparator: ezetimibe and simvastatin | DRUG | ezetimibe/simvastatin 10/20mg tablet. Treatment time will be \~40 additional weeks for a total of 64 weeks |
| Comparator: placebo | DRUG | - |
| ezetimibe/simvastatin | DRUG | Ezetimibe/simvastatin 10/40 mg per day from randomization through the end of participation. As per the original protocol, if LDL-C response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped). |
| Placebo for simvastatin 40 mg | DRUG | one or two tablets orally daily |
| Placebo for ezetimibe 10 mg/simvastatin 40 mg combination | DRUG | one tablet orally daily. |
| Simvastatin 20 mg | DRUG | 1 x 20-mg tablet, provided as open-label study treatment |
| Ezetimibe Placebo | DRUG | 1 tablet matching ezetimibe 10-mg tablet, provided as blinded study treatment |
| Simvastatin Placebo | DRUG | 1 tablet matching 20-mg simvastatin tablet, provided as blinded study treatment |
| Ezetimibe + Simvastatin | DRUG | ezetimibe 10 mg plus simvastatin 20 mg once daily for 8 weeks |
| Comparator: Placebo (unspecified) | DRUG | matching placebo tablet. Duration of Treatment 31 Weeks. |
| Ezetimibe + Atorvastatin | DRUG | oral tablets: ezetimibe 10 mg + atorvastatin 10 mg once daily for 6 weeks |
| ezetimibe (plus simvastatin) | DRUG | oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months |
| placebo (plus simvastatin) | DRUG | tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months |
| Atovastatin | DRUG | Atorvastatin 10, 20, and 40 mg tablets at a daily dose of 10 to 80 mg |
| Simivastatin | DRUG | Once daily administration at dose to be determined |
| Statin | DRUG | Statin administered orally once daily at dose determined by treatment prior to enrollment by personal physician |
| Atorvastatin 80 mg | DRUG | - |
| Ezetimibe/atorvastatin 10mg/10mg FDC | DRUG | Ezetimibe/atorvastatin 10mg/10mg FDC tablet given orally after an overnight fast (at least 10 hours). |
| Atorvastatin 10mg | DRUG | Atorvastatin 10mg given orally after an overnight fast (at least 10 hours). |
| Atorvastatin 80mg | DRUG | Atorvastatin 80mg tablet given orally after an overnight fast (at least 10 hours). |
| Ezetimibe/atorvastatin 10mg/80mg FDC | DRUG | Ezetimibe/atorvastatin 10mg/80mg FDC tablet given orally after an overnight fast (at least 10 hours). |
| SCH 58235 | DRUG | SCH 58235 10 mg (once daily) |
| pitavastatin | DRUG | Pitavastatin 2 mg (once daily) |
| Comparator: cyclosporine | DRUG | single oral dose of cyclosporine 100 mg capsules on Day 1 or Day 7. |
| Ezetimibe + Rosuvastatin | DRUG | oral tablets; rosuvastatin 10 mg + ezetimibe 10 mg, once daily for 14 days |
Inclusion Criteria: * Japanese * Outpatient with hypercholesterolemia * Female participant who is of reproductive potential has to agree to remain abstinent or use (or partner use) two acceptable methods of birth control from date of signed informed consent to the 14 days after the last dose of stu...
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| United Therapeutics Corporation | UTHR | 1 | PHASE3 | Ralinepag |
| Roivant Sciences Ltd. | ROIV | 3 | PHASE3 | Mosliciguat |
| Genentech, Inc. | RHHBY | 1 | PHASE2 | Selnoflast |
| Verve Therapeutics, Inc. | VERV | 2 | PHASE2 | VERVE-102 |
Ezetimibe + rosuvastatin is used to treat high cholesterol conditions, including primary hypercholesterolemia, hypercholesterolemia, hyperlipidemia, and atherosclerosis. It is a small molecule combination therapy developed by Organon & Co. (OGN). The drug is in Phase 3 clinical development.
Ezetimibe + rosuvastatin targets NPC1L1, a protein involved in cholesterol absorption. Ezetimibe acts as an inhibitor of NPC1L1, while rosuvastatin is a statin that inhibits HMG-CoA reductase. This combination aims to reduce cholesterol levels through complementary mechanisms.
Ezetimibe + rosuvastatin is being developed by Organon & Co., which trades under the ticker OGN. Organon is a global healthcare company focused on women's health and other therapeutic areas.
Ezetimibe + rosuvastatin is in Phase 3 clinical development. It has completed 22 trials with a total enrollment of 26,110 participants. The trials were randomized, double-blind, and placebo-controlled. No active trials are currently listed.
Ezetimibe + rosuvastatin has been studied in completed Phase 3 trials, including NCT03885921 in homozygous familial hypercholesterolemia, NCT03882996 in hypercholesterolemia, NCT03882905 in primary hypercholesterolemia, and NCT03882892 in hypercholesterolemia. All trials are completed.