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Atorvastatin

Phase 3

Familial Hypercholesterolemia | Small molecule | Metabolic |Organon & Co.|Last Updated: May 16, 2024

Target and mechanism

ModalitySmall molecule

Also known as Atorvastatin 10mg, Comparator: atorvastatin

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials1
Total Enrollment50

FDA Designations

No designations recorded

Clinical trial landscape

Atorvastatin · 7 trials · 2 indications

Phase 3 7
NCT01370590A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1)Hypercholesterolemia
COMPLETED406 Analytics
NCT01370603A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/40 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 40 mg Tablets in Participants With High Cholesterol (MK-0653C-190 AM1)Hypercholesterolemia
COMPLETED328 Analytics
NCT00535405A Study to Assess the Cholesterol Lowering Effect of Ezetimibe/Simvastatin Combination Tablet Compared to Another Cholesterol Lowering Drug in Elderly Patients With High Cholesterol at High or Moderately High Risk for Coronary Heart Disease (0653A-128)Hypercholesterolemia
COMPLETED1,289 Analytics
NCT00276458To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg (0653-079)(COMPLETED)Hypercholesterolemia
COMPLETED196 Analytics
NCT00276484To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 40 mg (0653-090)Hypercholesterolemia
COMPLETED579 Analytics
NCT03884452Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)Familial Hypercholesterolemia
COMPLETED50 Analytics
NCT03867318Efficacy and Safety Study of Ezetimibe (SCH 58235, MK-0653) in Addition to Atorvastatin in Participants With Coronary Heart Disease or Multiple Cardiovascular Risk Factors (P00693/MK-0653-030)Hypercholesterolemia
COMPLETED621 Analytics
PHASE3COMPLETED
A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1)
HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/40 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 40 mg Tablets in Participants With High Cholesterol (MK-0653C-190 AM1)
HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
A Study to Assess the Cholesterol Lowering Effect of Ezetimibe/Simvastatin Combination Tablet Compared to Another Cholesterol Lowering Drug in Elderly Patients With High Cholesterol at High or Moderately High Risk for Coronary Heart Disease (0653A-128)
HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg (0653-079)(COMPLETED)
HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 40 mg (0653-090)
HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
Familial HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety Study of Ezetimibe (SCH 58235, MK-0653) in Addition to Atorvastatin in Participants With Coronary Heart Disease or Multiple Cardiovascular Risk Factors (P00693/MK-0653-030)
HypercholesterolemiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment
Baseline and Week 6

Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

Percent Change From Baseline in Low Density Lipoprotein (LDL-C) at Week 12
Baseline and 12 weeks
Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 6
6 weeks

\[(6 week value - baseline value)/baseline value\]\*100%.

Percent Change From Baseline to Week 6 in Low-Density Lipoprotein (LDL)-C
Baseline and 6 weeks

Percent Change in LDL-C = \[(week 6 value - baseline value)/baseline value\]\*100%

Percent change from baseline in Low Density Lipoprotein Cholesterol (LDL-C) measured directly
Baseline and Up to Week 12
Percentage of participants with an Adverse Event (AE)
Up to Week 12
Percentage of Participants Achieving Target Low-Density-Lipoprotein Cholesterol (LDL-C) Levels of ≤100 mg/dL
Week 14

The percentage of participants achieving the target low-density-lipoprotein cholesterol (LDL-C) levels (≤100 mg/dL \[2.59 mmol/L\]) as determined from blood samples following a standard ultracentrifugation/precipitation procedure (β-quantification).

Percentage of Participants With an Adverse Event
14 weeks (Up to 16 weeks)

An adverse event (AE) is defined as any physical or clinical change or disease reported by a participant or observed by the investigator or member of the staff at any time during the study, regardless of potential relationship to study treatment, and included onset or discovery of new illness and exacerbation of any pre-existing condition.

Percentage of Participants Who Discontinued the Study due to an Adverse Event
14 weeks (Up to 16 weeks)

An adverse event (AE) is defined as any physical or clinical change or disease reported by a participant or observed by the investigator or member of the staff at any time during the study, regardless of potential relationship to study treatment, and included onset or discovery of new illness and exacerbation of any pre-existing condition.

Secondary Endpoints

Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment
Baseline and Week 6
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment
Baseline and Week 6
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment
Baseline and Week 6
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelCROSSOVER
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Ezetimibe and atorvastatinACTIVE_COMPARATORMedication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including 10 mg ezetimibe, 20 mg atorvastatin, and placebo to ezetimibe/atorvastatin.
Ezetimibe/atorvastatin combinationEXPERIMENTALMedication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including ezetimibe/atorvastatin 10 mg/20 mg, placebo to ezetimibe, and placebo to atorvastatin.
1EXPERIMENTALEach patient will receive 1 active treatment dose \& 2 Placebo (Pbo) doses or 2 active treatment doses \& 1 Pbo dose at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 12 weeks.
2EXPERIMENTALEach patient will receive 1 active treatment dose \& 2 Pbo doses or 2 active treatment doses \& 1 Pbo dose at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 12 weeks.
3EXPERIMENTALEach patient will receive 1 active treatment dose \& 2 Pbo doses or 2 active treatment doses \& 1 Pbo dose at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 12 weeks.
4EXPERIMENTALEach patient will receive 1 active treatment dose \& 2 Pbo doses or 2 active treatment doses \& 1 Pbo dose at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 12 weeks.
5EXPERIMENTALEach patient will receive 1 active treatment dose \& 2 Pbo doses or 2 active treatment doses \& 1 Pbo dose at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 12 weeks.
Atorvastatin 80 mgEXPERIMENTAL80 mg atorvastatin taken orally, once daily for 12 weeks
Ezetimibe + Atorvastatin 40 mgEXPERIMENTAL10 mg ezetimibe and 40 mg atorvastatin taken orally, once daily for 12 weeks
Ezetimibe + Atorvastatin 80 mgEXPERIMENTAL10 mg ezetimibe and 80 mg atorvastatin taken orally, once daily for 12 weeks
Simvastatin 80 mgEXPERIMENTAL80 mg simvastatin taken orally, once daily for 12 weeks
Ezetimibe + Simvastatin 40 mgEXPERIMENTAL10 mg ezetimibe and 40 mg simvastatin taken orally, once daily for 12 weeks
Ezetimibe + Simvastatin 80 mgEXPERIMENTAL10 mg ezetimibe and 80 mg simvastatin taken orally, once daily for 12 weeks
Atorvastatin MonotherapyEXPERIMENTALParticipants receive double-blind atorvastatin 10 mg once daily (QD) via oral tablet PLUS open-label atorvastatin 10 mg QD via oral tablet for the entire duration of the study. Double-blind atorvastatin is to be added to the regimen for participants not achieving LDL-C target (≤100 mg/dL; 2.59 mmol/L). The maximum possible total daily dose of atorvastatin received in this group is 80 mg (10 mg open label plus 70 mg double blind).
Ezetimibe + AtorvastatinEXPERIMENTALParticipants receive double-blind ezetimibe 10 mg QD via oral tablet PLUS open-label atorvastatin 10 mg QD via oral tablet for the entire duration of the study. Double-blind atorvastatin is to be added to the regimen for participants not achieving LDL-C target (≤100 mg/dL; 2.59 mmol/L). The maximum possible total daily dose of atorvastatin received in this group is 40 mg (10 mg open label plus 30 mg double blind).

Interventions

NameTypeDescription
AtorvastatinDRUG20 mg tablet administered orally once daily
EzetimibeDRUG10 mg tablet administered orally once daily
Ezetimibe/atorvastatinDRUGEzetimibe/atorvastatin 10 mg/20 mg combination tablet administered orally once daily
Placebo to atorvastatinDRUGAdministered orally once daily
Placebo to ezetimibeDRUGAdministered orally once daily
Placebo to ezetimibe/atorvastatinDRUGAdministered orally once daily
Atorvastatin 10 mgDRUGAtorvastatin 10 mg and Placebo for ezetimibe and placebo for simvastatin once daily for 12 weeks
Ezetimibe 10 mg/simvastatin 20 mgDRUGEzetimibe 10 mg/simvastatin 20 mg and Placebo for atorvastatin once daily for 12 weeks
Atorvastatin 20 mgDRUGAtorvastatin 20 mg and Placebo for ezetimibe and placebo for simvastatin once daily for 12 weeks
Ezetimibe 10 mg/simvastatin 40 mgDRUGEzetimibe 10 mg/simvastatin 40 mg and Placebo for atorvastatin once daily for 12 weeks
Atorvastatin 40 mgDRUGAtorvastatin 40 mg and Placebo for ezetimibe and placebo for simvastatin once daily for 12 weeks
Comparator: atorvastatinDRUGAtorvastatin 40mg tablet po qd (by mouth, once a day) for 6 weeks
Comparator: PlaceboDRUGAtorvastatin 20mg Pbo and ezetimibe 10mg Pbo tablets po qd (by mouth, once a day). for 6 weeks
Comparator: ezetimibeDRUGAtorvastatin 20mg and ezetimibe 10mg tablets po qd (by mouth, once a day). for 6 weeks.
Comparator: Placebo.DRUGAtorvastatin 40mg Pbo tablets po qd (by mouth, once a day). for 6 weeks.
SimvastatinDRUGTablets taken orally once daily in the morning or evening
Placebo for EzetimibeDRUGTablets taken orally once daily in the morning or evening
Placebo for AtorvastatinDRUGSingle placebo tablet administered orally QD
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Eligibility Criteria

Age Range18 Years to 79 Years
SexALL
Healthy VolunteersNo

Inclusion criteria: * At low, moderate, or moderately high cardiovascular risk (according to National Cholesterol Education Program adult treatment panel III \[NCEP ATP III\] guidelines) and either statin-naïve with LDL-C ≥130 mg/dL for low risk or ≥100 mg/dL for moderate or moderately high risk OR...

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