Trial Outcomes & Findings for A Clinical Trial to Assess the Efficacy and Safety of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-383) (NCT NCT02550288)
NCT ID: NCT02550288
Last Updated: 2024-05-16
Results Overview
Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The change from baseline was calculated.
COMPLETED
PHASE3
309 participants
Baseline and Week 12
2024-05-16
Participant Flow
Study consisted of screening, a 2-week placebo run-in and a 12-week treatment period.
Participant milestones
| Measure |
Ezetimibe 10 mg
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
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
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
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
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
35
|
68
|
69
|
68
|
69
|
|
Overall Study
COMPLETED
|
33
|
65
|
68
|
65
|
66
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
1
|
3
|
3
|
Reasons for withdrawal
| Measure |
Ezetimibe 10 mg
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
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
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
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
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Protocol Violation
|
2
|
2
|
1
|
0
|
3
|
|
Overall Study
Participant moved
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Clinical Trial to Assess the Efficacy and Safety of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-383)
Baseline characteristics by cohort
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
Total
n=309 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
57.1 years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
58.9 years
STANDARD_DEVIATION 8.6 • n=7 Participants
|
58.3 years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
58.7 years
STANDARD_DEVIATION 10.4 • n=4 Participants
|
57.9 years
STANDARD_DEVIATION 11.0 • n=21 Participants
|
58.3 years
STANDARD_DEVIATION 10.0 • n=8 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
37 Participants
n=21 Participants
|
162 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
32 Participants
n=21 Participants
|
147 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: All participants who received at least 1 dose of study treatment, and had a baseline observation or at least 1 post-baseline observation. One participant who received misallocated study medication during placebo run-in period was excluded from the main population for the analysis of efficacy data.
Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The change from baseline was calculated.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=68 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
|
-19.3 Percentage Change
Interval -22.7 to -15.8
|
-44.0 Percentage Change
Interval -46.5 to -41.6
|
-49.1 Percentage Change
Interval -51.5 to -46.7
|
-55.6 Percentage Change
Interval -58.0 to -53.2
|
-59.2 Percentage Change
Interval -61.6 to -56.8
|
PRIMARY outcome
Timeframe: up to 14 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
Gastrointestinal-related AEs included all preferred terms within system organ class of Gastrointestinal Disorders except Chapped Lips and Toothache.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience 1 or More Gastrointestinal-related Adverse Events (AEs)
|
5.7 Percentage of Participants
|
0.0 Percentage of Participants
|
8.7 Percentage of Participants
|
7.4 Percentage of Participants
|
7.2 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 14 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience 1 or More Gallbladder-related AEs
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 14 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience 1 or More Allergic Reaction or Rash AEs
|
0.0 Percentage of Participants
|
2.9 Percentage of Participants
|
2.9 Percentage of Participants
|
0.0 Percentage of Participants
|
1.4 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 14 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience 1 or More Hepatitis-related AEs
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) ≥3 Times Upper Limit of Normal (ULN)
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience Consecutive Elevations in Aspartate Aminotransferase (AST) ≥3 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience Consecutive Elevations in ALT and/or AST ≥3 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience Consecutive Elevations in ALT ≥5 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=69 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience Consecutive Elevations in AST ≥5 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Have Consecutive Elevations in ALT and/or AST ≥5 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience Consecutive Elevations in ALT ≥10 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Experience Consecutive Elevations in AST ≥10 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=69 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Have Consecutive Elevations in ALT and/or AST ≥10 Times ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.5 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
Percentage of Participants with Potential Hy's Law Condition (defined as serum ALT or serum AST elevations \>3xULN, with serum alkaline phosphatase \<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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants With Potential Hy's Law Condition
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Have Elevations in Creatine Kinase (CK) ≥10xULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
1.4 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Have Elevations in CK ≥10xULN With Muscle Symptoms
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
PRIMARY outcome
Timeframe: up to 12 weeksPopulation: All randomized participants who received at least 1 dose of actual study treatment.
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.
Outcome measures
| Measure |
Ezetimibe 10 mg
n=35 Participants
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 Participants
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
n=69 Participants
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Have Elevations in CK ≥10xULN and Drug-Related Muscle Symptoms
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
Adverse Events
Ezetimibe 10 mg
Atorvastatin 10 mg
Atorvastatin 20 mg
Ezetimibe 10 mg + Atorvastatin 10 mg
Ezetimibe 10 mg + Atorvastatin 20 mg
Serious adverse events
| Measure |
Ezetimibe 10 mg
n=35 participants at risk
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 participants at risk
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
n=69 participants at risk
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 participants at risk
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
n=69 participants at risk
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/35 • up to 14 weeks
|
1.5%
1/68 • Number of events 1 • up to 14 weeks
|
0.00%
0/69 • up to 14 weeks
|
0.00%
0/68 • up to 14 weeks
|
0.00%
0/69 • up to 14 weeks
|
Other adverse events
| Measure |
Ezetimibe 10 mg
n=35 participants at risk
1 ezetimide 10 mg tablet, 2 atorvastatin 10 mg placebo capsules orally once daily for 12 weeks.
|
Atorvastatin 10 mg
n=68 participants at risk
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
n=69 participants at risk
2 atorvastatin 10 mg capsules and 1 ezetimide 10 mg placebo tablet orally, once daily for 12 weeks.
|
Ezetimibe 10 mg + Atorvastatin 10 mg
n=68 participants at risk
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
n=69 participants at risk
1 Ezetimibe 10 mg tablet and 2 atorvastatin 10 mg capsules orally, once daily for 12 weeks
|
|---|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
14.3%
5/35 • Number of events 7 • up to 14 weeks
|
5.9%
4/68 • Number of events 4 • up to 14 weeks
|
11.6%
8/69 • Number of events 8 • up to 14 weeks
|
14.7%
10/68 • Number of events 11 • up to 14 weeks
|
17.4%
12/69 • Number of events 15 • up to 14 weeks
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/35 • up to 14 weeks
|
1.5%
1/68 • Number of events 1 • up to 14 weeks
|
1.4%
1/69 • Number of events 1 • up to 14 weeks
|
1.5%
1/68 • Number of events 1 • up to 14 weeks
|
5.8%
4/69 • Number of events 4 • up to 14 weeks
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
- Publication restrictions are in place
Restriction type: OTHER