Hypercholesterolemia
Conditions
Brief summary
This study will compare the lipid-altering efficacy and safety of switching to co-administration of ezetimibe and atorvastatin versus treatment with atorvastatin or rosuvastatin in high cardiovascular risk patients with hypercholesterolemia who have not achieved specified low-density lipoprotein cholesterol (LDL-C) levels. The primary hypothesis is that the co-administration of ezetimibe 10 mg and atorvastatin 10 mg will be superior to both atorvastatin 20 mg and rosuvastatin 10 mg with respect to the percentage reduction in low-density lipoprotein-cholesterol (LDL-C) after 6 weeks of treatment.
Detailed description
This is a 18 week randomized, double-blind, active-controlled, multicenter study composed of a 6 week screening/run-in and 12 week double-blind treatment period (composed of 2 phases; each 6 weeks in duration). Only those participants who do not meet low density lipoprotein-cholesterol (LDL-C) goals at the end of Phase I (Week 6), were eligible to continue into Phase II (Week 12).
Interventions
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Patient is at high cardiovascular risk and meets one of the following conditions: has never taken lipid-lowering therapy or has been off such therapy for at least 6 weeks; or, is currently taking a stable dose of certain lipid-lowering agents * Patient is willing to maintain a cholesterol lowering diet during the study * Female patients receiving non-cyclical hormone therapy have maintained a stable dose and regimen for at least 8 weeks and are willing to continue the same regimen during the study
Exclusion criteria
* Patient is Asian * Patient routinely has more than 2 alcoholic drinks per day * Female patient is pregnant or breastfeeding * Patient has congestive heart failure * Patient has had a myocardial infarction, coronary bypass surgery, angioplasty, or acute coronary syndrome within 3 months of screening * Patient has uncontrolled cardiac arrhythmias * Patient has had a partial ileal or gastric bypass or other significant intestinal malabsorption * Patient has uncontrolled high blood pressure * Patient has kidney disease * Patient has any disease known to influence blood lipid levels * Patient has any disorders of the blood, digestive system, or nervous system including stroke and degenerative disease that would limit study participation * Patient has poorly controlled or newly diagnosed diabetes * Patient is known to be HIV positive * Patient has a history of cancer in the last 5 years, except certain skin and cervical cancers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I) | Baseline and Week 6 (end of Phase I ) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I) | Week 6 (End of Phase I) | — |
| Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II) | Week 12 (End of Phase II) | — |
| Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I) | Week 6 (End of Phase I) | — |
| Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II) | Week 12 (end of Phase II) | — |
| Percent Change From Baseline in Total Cholesterol (TC) (Phase I) | Baseline and Week 6 (end of Phase I) | TC 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 |
| Percent Change From Baseline in Total Cholesterol (TC) (Phase II) | Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II) | TC levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in Triglycerides (TG) (Phase I) | Baseline and Week 6 (end of Phase I) | TG 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. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment. |
| Percent Change From Baseline in Triglycerides (TG) (Phase II) | Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II) | TG levels measured at Baseline (Week 6: end of Phase I) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment. |
| Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I) | Baseline and Week 6 (end of Phase I) | HDL-C 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 |
| Percent Change From Baseline in HDL-C (Phase II) | Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II) | HDL-C levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I) | Baseline and Week 6 (end of Phase I) | Apo-B 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 |
| Percent Change From Baseline in Apo B (Phase II) | Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II) | Apo-B levels measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I) | Baseline and Week 6 (end of Phase I) | Apo-A-I 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 |
| Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II). | Baseline (Week 6) and Week 12 | LDL-C levels measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12). Baseline was defined as the average of the values at Visits 5 and 6. 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). |
| Percent Change From Baseline in Non-HDL-C (Phase I) | Baseline and Week 6 (end of Phase I) | Non-HDL-C 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 |
| Percent Change From Baseline in Non-HDL-C (Phase II) | Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II) | Non-HDL-C levels calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in TC/HDL-C Ratio (Phase I) | Baseline and Week 6 (end of Phase I) | TC/HDL-C ratio calculated 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 |
| Percent Change From Baseline in TC/HDL-C Ratio (Phase II) | Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II) | TC/HDL-C Ratio calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I) | Baseline and Week 6 (end of Phase I) | LDL-C/HDL-C ratio calculated 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 |
| Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II) | Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II) | LDL-C/HDL-C Ratio calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I) | Baseline and Week 6 (end of Phase I) | Apo B/Apo A-I ratio calculated 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 |
| Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II) | Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II) | Apo B/Apo A-I Ratio calculated at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I) | Baseline and Week 6 (end of Phase I) | Non HDL-C/HDL-C ratio calculated 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 |
| Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II) | Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II) | Non HDL-C/HDL-C Ratio calculated at baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
| Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I) | Baseline and Week 6 (end of Phase I) | hs-CRP 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. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment. |
| Percent Change From Baseline in Hs-CRP (Phase II) | Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II) | hs-CRP measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment. |
| Percent Change From Baseline in Apo A-I (Phase II) | Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II) | Apo-A-I levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. |
Participant flow
Pre-assignment details
Participants in the Atorvastatin 20mg and Rosuvastatin 10mg arms who did not meet low density lipoprotein-cholesterol goals during Phase I were eligible for Phase II. Approximately 25% of participants in the ezetimibe 10mg+atorvastatin10mg arm continued to Phase II regardless of LDL-C control but were not included in any of the statistical analyses
Participants by arm
| Arm | Count |
|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg Co-administration of EZ 10 mg tablet + Atorva 10 mg tablet; once daily for 6 weeks | 120 |
| Phase I: Atorvastatin 20 mg Atorvastatin 20 mg tablet once daily for 6 weeks | 483 |
| Phase I: Rosuvastatin 10 mg Rosuvastatin 10 mg tablet once daily for 6 weeks | 944 |
| Total | 1,547 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Phase I | Adverse Event | 1 | 11 | 12 | 0 | 0 | 0 | 0 | 0 |
| Phase I | Lost to Follow-up | 0 | 3 | 6 | 0 | 0 | 0 | 0 | 0 |
| Phase I | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase I | Protocol Violation | 0 | 3 | 9 | 0 | 0 | 0 | 0 | 0 |
| Phase I | Withdrawal by Subject | 2 | 10 | 29 | 0 | 0 | 0 | 0 | 0 |
| Phase II | Adverse Event | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 |
| Phase II | Lost to Follow-up | 0 | 0 | 0 | 1 | 2 | 0 | 2 | 1 |
| Phase II | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Phase II | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 |
| Phase II | Withdrawal by Subject | 0 | 0 | 0 | 0 | 4 | 2 | 5 | 4 |
Baseline characteristics
| Characteristic | Total | Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Phase I: Atorvastatin 20 mg | Phase I: Rosuvastatin 10 mg |
|---|---|---|---|---|
| Age, Customized 20 to 29 years | 6 Participants | 0 Participants | 4 Participants | 2 Participants |
| Age, Customized <20 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Customized 30 to 39 years | 39 Participants | 1 Participants | 13 Participants | 25 Participants |
| Age, Customized 40 to 49 years | 165 Participants | 16 Participants | 50 Participants | 99 Participants |
| Age, Customized 50 to 59 years | 531 Participants | 37 Participants | 170 Participants | 324 Participants |
| Age, Customized 60 to 64 years | 297 Participants | 27 Participants | 87 Participants | 183 Participants |
| Age, Customized ≥65 years | 508 Participants | 39 Participants | 159 Participants | 310 Participants |
| Sex: Female, Male Female | 813 Participants | 71 Participants | 253 Participants | 489 Participants |
| Sex: Female, Male Male | 734 Participants | 49 Participants | 230 Participants | 455 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 120 | 0 / 480 | 0 / 939 | 0 / 28 | 0 / 124 | 0 / 124 | 0 / 231 | 0 / 205 |
| serious Total, serious adverse events | 0 / 120 | 3 / 480 | 10 / 939 | 0 / 28 | 2 / 124 | 2 / 124 | 5 / 231 | 1 / 205 |
Outcome results
Primary
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I)
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).
Time frame: Baseline and Week 6 (end of Phase I )
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participant who received at least one dose of study drug during Phase I and had a baseline or at least one measurement available during Phase I
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I) | -24.8 Percentage Change | Standard Deviation 23.6 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I) | -10.1 Percentage Change | Standard Deviation 20.8 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I) | -13.8 Percentage Change | Standard Deviation 22.8 |
p-value: <0.00195% CI: [-16.6, -8.7]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-12.9, -5.4]Multiple Imputation Robust Regression
Secondary
Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I)
Time frame: Week 6 (End of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I and had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I) | 56.3 Percentage of Participants | 4.55 |
| Phase I: Atorvastatin 20 mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I) | 37.4 Percentage of Participants | 2.23 |
| Phase I: Rosuvastatin 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I) | 43.6 Percentage of Participants | 1.64 |
p-value: <0.00195% CI: [1.62, 3.89]Logistic Regression Model
p-value: 0.00795% CI: [1.17, 2.67]Logistic Regression Model
Secondary
Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II)
Time frame: Week 12 (End of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II and had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II) | 55.8 Percentage of Participants | 4.53 |
| Phase I: Atorvastatin 20 mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II) | 34.1 Percentage of Participants | 4.28 |
| Phase I: Rosuvastatin 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II) | 53.5 Percentage of Participants | 3.3 |
| Phase II: Rosuvastatin 20mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II) | 35.8 Percentage of Participants | 3.38 |
| Phase II: EZ 10mg+Atorva 10mg | Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II) | NA Percentage of Participants | — |
p-value: <0.00195% CI: [1.55, 4.73]Logistic regression Model
p-value: <0.00195% CI: [1.56, 3.63]Logistic Regression Model
Secondary
Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I)
Time frame: Week 6 (End of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I and had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I) | 19.3 Percentage of Participants | 3.62 |
| Phase I: Atorvastatin 20 mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I) | 3.0 Percentage of Participants | 0.78 |
| Phase I: Rosuvastatin 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I) | 6.6 Percentage of Participants | 0.82 |
p-value: <0.00195% CI: [4.56, 19.62]Logistic Regression Model
p-value: <0.00195% CI: [2.23, 6.82]Logistic Regression Model
Secondary
Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II)
Time frame: Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II and had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II) | 18.3 Percentage of Participants | 3.53 |
| Phase I: Atorvastatin 20 mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II) | 0.8 Percentage of Participants | 0.81 |
| Phase I: Rosuvastatin 10 mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II) | 15.4 Percentage of Participants | 2.39 |
| Phase II: Rosuvastatin 20mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II) | 3.0 Percentage of Participants | 1.2 |
| Phase II: EZ 10mg+Atorva 10mg | Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II) | NA Percentage of Participants | — |
p-value: 0.00195% CI: [3.64, 211.83]Logistic Regression Model
p-value: <0.00195% CI: [2.85, 17.56]Logistic Regression Model
Secondary
Percent Change From Baseline in Apo A-I (Phase II)
Apo-A-I levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Apo A-I (Phase II) | 1.6 Percentage Change | Standard Deviation 11.9 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Apo A-I (Phase II) | 1.4 Percentage Change | Standard Deviation 14.1 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Apo A-I (Phase II) | -0.6 Percentage Change | Standard Deviation 14.4 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Apo A-I (Phase II) | 0.0 Percentage Change | Standard Deviation 16 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Apo A-I (Phase II) | -0.7 Percentage Change | Standard Deviation 14.3 |
p-value: 0.73995% CI: [-2.5, 3.6]Multiple Imputation Robust Regression
p-value: 0.4195% CI: [-3.3, 1.3]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I)
Apo B/Apo A-I ratio calculated 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I) | -13.0 Percentage Change | Standard Deviation 22.3 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I) | -4.8 Percentage Change | Standard Deviation 18.9 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I) | -8.8 Percentage Change | Standard Deviation 23 |
p-value: <0.00195% CI: [-10, -2.5]Multiple Imputation Robust Regression
p-value: 0.05295% CI: [-7.1, 0]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II)
Apo B/Apo A-I Ratio calculated at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II) | -11.2 Percentage Change | Standard Deviation 26.2 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II) | -6.4 Percentage Change | Standard Deviation 19.4 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II) | -11.2 Percentage Change | Standard Deviation 27.5 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II) | -5.4 Percentage Change | Standard Deviation 21.5 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II) | -6.7 Percentage Change | Standard Deviation 11.3 |
p-value: 0.02495% CI: [-10.8, -0.8]Multiple Imputation Robust Regression
p-value: 0.00295% CI: [-9.9, -2.3]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Apo B (Phase II)
Apo-B levels measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Apo B (Phase II) | -12.0 Percentage Change | Standard Deviation 26.5 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Apo B (Phase II) | -6.3 Percentage Change | Standard Deviation 19.6 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Apo B (Phase II) | -14.0 Percentage Change | Standard Deviation 25.1 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Apo B (Phase II) | -4.9 Percentage Change | Standard Deviation 21.8 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Apo B (Phase II) | -4.0 Percentage Change | Standard Deviation 16.8 |
p-value: 0.07995% CI: [-9.2, 0.5]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-11.4, -4.1]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I)
Apo-A-I 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I) | -0.6 Percentage Change | Standard Deviation 13.1 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I) | -1.9 Percentage Change | Standard Deviation 12.5 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I) | 1.4 Percentage Change | Standard Deviation 13 |
p-value: 0.15695% CI: [-0.6, 3.8]Multiple Imputation Robust Regression
p-value: 0.42595% CI: [-2.9, 1.2]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I)
Apo-B 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I) | -12.1 Percentage Change | Standard Deviation 20.7 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I) | -6.1 Percentage Change | Standard Deviation 20.7 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I) | -7.6 Percentage Change | Standard Deviation 20.1 |
p-value: 0.00395% CI: [-8.8, -1.8]Multiple Imputation Robust Regression
p-value: 0.01195% CI: [-7.7, -1]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in HDL-C (Phase II)
HDL-C levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in HDL-C (Phase II) | 0.9 Percentage Change | Standard Deviation 14.1 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in HDL-C (Phase II) | 1.0 Percentage Change | Standard Deviation 16 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in HDL-C (Phase II) | -0.8 Percentage Change | Standard Deviation 13.7 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in HDL-C (Phase II) | 0.0 Percentage Change | Standard Deviation 15.2 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in HDL-C (Phase II) | 0.0 Percentage Change | Standard Deviation 11.7 |
p-value: 0.5295% CI: [-4.2, 2.1]Multiple Imputation Robust Regression
p-value: 0.56795% CI: [-3.1, 1.7]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I)
HDL-C 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I) | 0.9 Percentage Change | Standard Deviation 11.9 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I) | -1.3 Percentage Change | Standard Deviation 11.6 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I) | 1.0 Percentage Change | Standard Deviation 13.1 |
p-value: 0.13395% CI: [-0.5, 4]Multiple Imputation Robust Regression
p-value: 0.6195% CI: [-2.7, 1.6]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I)
hs-CRP 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. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I and had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I) | -10.5 Percentage Change |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I) | -6.6 Percentage Change |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I) | -9.0 Percentage Change |
p-value: 0.61395% CI: [-18.9, 11.1]Constrained Longitudinal Data Analysis
p-value: 0.83195% CI: [-15.7, 12.6]Constrained Longitudinal Data Analysis
Secondary
Percent Change From Baseline in Hs-CRP (Phase II)
hs-CRP measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
Time frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II and had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Hs-CRP (Phase II) | -19.5 Percentage Change |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Hs-CRP (Phase II) | -6.4 Percentage Change |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Hs-CRP (Phase II) | -10.9 Percentage Change |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Hs-CRP (Phase II) | 0.7 Percentage Change |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Hs-CRP (Phase II) | NA Percentage Change |
p-value: 0.18795% CI: [-32.6, 6.4]Constrained Longitudinal Data Analysis
p-value: 0.15395% CI: [-27.7, 4.4]Constrained Longitudinal Data Analysis
Secondary
Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I)
LDL-C/HDL-C ratio calculated 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I) | -23.9 Percentage Change | Standard Deviation 23.6 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I) | -7.1 Percentage Change | Standard Deviation 23.2 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I) | -14.7 Percentage Change | Standard Deviation 26.9 |
p-value: <0.00195% CI: [-11.9, -3.6]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-18.1, -9.3]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II)
LDL-C/HDL-C Ratio calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II) | -20.6 Percentage Change | Standard Deviation 31.4 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II) | -8.2 Percentage Change | Standard Deviation 20.6 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II) | -18.2 Percentage Change | Standard Deviation 31.6 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II) | -7.5 Percentage Change | Standard Deviation 21.5 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II) | -4.5 Percentage Change | Standard Deviation 22.9 |
p-value: <0.00195% CI: [-15.8, -4.9]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-12.5, -4.2]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II).
LDL-C levels measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12). Baseline was defined as the average of the values at Visits 5 and 6. 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).
Time frame: Baseline (Week 6) and Week 12
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II). | -16.4 Percentage Change | Standard Deviation 31.1 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II). | -8.1 Percentage Change | Standard Deviation 23.3 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II). | -19.3 Percentage Change | Standard Deviation 32.1 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II). | -8.4 Percentage Change | Standard Deviation 20.8 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II). | 2.4 Percentage Change | Standard Deviation 27.4 |
p-value: <0.00195% CI: [-15.9, -5.1]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-13.6, -5.5]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I)
Non HDL-C/HDL-C ratio calculated 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I) | -18.9 Percentage Change | Standard Deviation 23.9 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I) | -6.3 Percentage Change | Standard Deviation 22.8 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I) | -12.2 Percentage Change | Standard Deviation 25.9 |
p-value: <0.00195% CI: [-14.9, -6.4]Multiple Imputation Robust Regression
p-value: 0.00295% CI: [-10.2, -2.2]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II)
Non HDL-C/HDL-C Ratio calculated at baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II) | -18.2 Percentage Change | Standard Deviation 29.5 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II) | -8.8 Percentage Change | Standard Deviation 18.8 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II) | -16.3 Percentage Change | Standard Deviation 32.3 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II) | -5.9 Percentage Change | Standard Deviation 23.4 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II) | -1.9 Percentage Change | Standard Deviation 12.9 |
p-value: <0.00195% CI: [-14.8, -3.9]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-12.6, -4.2]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Non-HDL-C (Phase I)
Non-HDL-C 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Non-HDL-C (Phase I) | -18.0 Percentage Change | Standard Deviation 22.3 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C (Phase I) | -7.9 Percentage Change | Standard Deviation 17.6 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C (Phase I) | -11.1 Percentage Change | Standard Deviation 19.8 |
p-value: <0.00195% CI: [-13.6, -6.6]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-10.9, -4.3]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Non-HDL-C (Phase II)
Non-HDL-C levels calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Non-HDL-C (Phase II) | -17.5 Percentage Change | Standard Deviation 26.1 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Non-HDL-C (Phase II) | -5.5 Percentage Change | Standard Deviation 16.6 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Non-HDL-C (Phase II) | -18.1 Percentage Change | Standard Deviation 29.4 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Non-HDL-C (Phase II) | -6.3 Percentage Change | Standard Deviation 18.5 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Non-HDL-C (Phase II) | -0.5 Percentage Change | Standard Deviation 17.7 |
p-value: <0.00195% CI: [-14, -4.5]Multiple Imputation Robust Regression
p-value: 0.00195% CI: [-13.5, -6.2]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in TC/HDL-C Ratio (Phase I)
TC/HDL-C ratio calculated 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase I) | -14.3 Percentage Change | Standard Deviation 17.9 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase I) | -4.5 Percentage Change | Standard Deviation 16.8 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase I) | -9.0 Percentage Change | Standard Deviation 19.1 |
p-value: <0.00195% CI: [-11.2, -4.9]Multiple Imputation Robust Regression
p-value: 0.00195% CI: [-7.8, -1.9]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in TC/HDL-C Ratio (Phase II)
TC/HDL-C Ratio calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase II) | -13.5 Percentage Change | Standard Deviation 21.7 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase II) | -6.5 Percentage Change | Standard Deviation 13.9 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase II) | -11.7 Percentage Change | Standard Deviation 23.3 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase II) | -4.0 Percentage Change | Standard Deviation 17.8 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in TC/HDL-C Ratio (Phase II) | -1.0 Percentage Change | Standard Deviation 9.6 |
p-value: <0.00195% CI: [-11, -2.8]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-9.4, -3.3]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Total Cholesterol (TC) (Phase I)
TC 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
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I or had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase I) | -13.6 Percentage Change | Standard Deviation 17 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase I) | -6.3 Percentage Change | Standard Deviation 14.1 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase I) | -8.2 Percentage Change | Standard Deviation 14.7 |
p-value: <0.00195% CI: [-9.7, -4.4]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-8.3, -3.3]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Total Cholesterol (TC) (Phase II)
TC levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6.
Time frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II or had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase II) | -10.2 Percentage Change | Standard Deviation 19.9 |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase II) | -2.9 Percentage Change | Standard Deviation 15.7 |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase II) | -13.1 Percentage Change | Standard Deviation 22.8 |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase II) | -5.0 Percentage Change | Standard Deviation 14 |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Total Cholesterol (TC) (Phase II) | 2.2 Percentage Change | Standard Deviation 15.4 |
p-value: <0.00195% CI: [-10.7, -3]Multiple Imputation Robust Regression
p-value: <0.00195% CI: [-10.2, -4.5]Multiple Imputation Robust Regression
Secondary
Percent Change From Baseline in Triglycerides (TG) (Phase I)
TG 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. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
Time frame: Baseline and Week 6 (end of Phase I)
Population: Efficacy analyses were performed using the Full Analysis Set (FAS). For Phase I this population consisted of all randomized participants who received at least 1 dose of study drug during Phase I, had a baseline measurement for Phase I and had at least 1 measurement after the start of study drug provided during Phase I.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Triglycerides (TG) (Phase I) | -6.0 Percentage Change |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Triglycerides (TG) (Phase I) | -3.9 Percentage Change |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Triglycerides (TG) (Phase I) | -1.1 Percentage Change |
p-value: 0.46695% CI: [-7.8, 3.5]Constrained Longitudinal Data Analysis
p-value: 0.08195% CI: [-10.3, 0.5]Constrained Longitudinal Analysis
Secondary
Percent Change From Baseline in Triglycerides (TG) (Phase II)
TG levels measured at Baseline (Week 6: end of Phase I) and after 6 weeks of study drug administration (Week 12; end of Phase II). Baseline was defined as the average of the values at Visits 5 and 6. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
Time frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
Population: Full Analysis Set (FAS). For Phase II this population consisted of all randomized participants who completed Phase I and were not adequately controlled at the end of Phase I, received at least 1 dose of study treatment during Phase II, had a baseline measurement for Phase II and had at least 1 measurement after the start of Phase II
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Phase I: Ezetimibe (EZ) 10 mg + Atorvastatin (Atorva) 10 mg | Percent Change From Baseline in Triglycerides (TG) (Phase II) | -5.9 Percentage Change |
| Phase I: Atorvastatin 20 mg | Percent Change From Baseline in Triglycerides (TG) (Phase II) | -3.1 Percentage Change |
| Phase I: Rosuvastatin 10 mg | Percent Change From Baseline in Triglycerides (TG) (Phase II) | -10.2 Percentage Change |
| Phase II: Rosuvastatin 20mg | Percent Change From Baseline in Triglycerides (TG) (Phase II) | -3.2 Percentage Change |
| Phase II: EZ 10mg+Atorva 10mg | Percent Change From Baseline in Triglycerides (TG) (Phase II) | NA Percentage Change |
p-value: 0.46695% CI: [-10.2, 4.7]Constrained Longitudinal Data Analysis
p-value: 0.01195% CI: [-12.6, -1.6]Constrained Longitudinal Data Analysis