Trial Outcomes & Findings for 8-Week PK/PD Atorvastatin Study In Children And Adolescents With Heterozygous Familial Hypercholesterolemia (NCT NCT00739999)
NCT ID: NCT00739999
Last Updated: 2021-03-15
Results Overview
Parent-metabolite population PK model built using sparse blood samples from both Tanner Stage 1 and Tanner Stage 2+. Blood sampling times: Weeks 2 and 6: single sample between 4 and 12 hours postdose; Weeks 4 and 8: predose, 1 hour, and 2 hours postdose. Plasma samples were analyzed for atorvastatin and active hydroxyacid metabolite (o-hydroxyatorvastatin) concentrations using a validated, sensitive, and specific high-performance liquid chromatography tandem mass spectrometric method. Data presented are the result of the model used.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
39 participants
Primary outcome timeframe
Week 2, Week 4, Week 6, Week 8
Results posted on
2021-03-15
Participant Flow
Subjects were enrolled at 3 medical centers and participated in the study between 02 December 2008 and 13 May 2009.
Forty-five subjects were screened, and 39 subjects were assigned to study treatment.
Participant milestones
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
Age 6 - 10 years, at Tanner Stage 1. Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target low-density lipoprotein cholesterol (LDL-C) was not attained.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
Age 10 - 17 years, at Tanner Stage 2+. Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
24
|
|
Overall Study
COMPLETED
|
15
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
8-Week PK/PD Atorvastatin Study In Children And Adolescents With Heterozygous Familial Hypercholesterolemia
Baseline characteristics by cohort
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=15 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=24 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
6-8 years
|
7 participants
n=5 Participants
|
0 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Age, Customized
9-10 years
|
6 participants
n=5 Participants
|
3 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Age, Customized
11-14 years
|
2 participants
n=5 Participants
|
14 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Age, Customized
15-17 years
|
0 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 2, Week 4, Week 6, Week 8Population: Pharmacokinetic (PK) concentration population: all enrolled and treated subjects who had ≥ 1 PK concentration assessed. Active hydroxyacid metabolite p-hydroxyatorvastatin was not included in the model as originally planned as \> 80% of samples were below detectable level at the doses used in this trial.
Parent-metabolite population PK model built using sparse blood samples from both Tanner Stage 1 and Tanner Stage 2+. Blood sampling times: Weeks 2 and 6: single sample between 4 and 12 hours postdose; Weeks 4 and 8: predose, 1 hour, and 2 hours postdose. Plasma samples were analyzed for atorvastatin and active hydroxyacid metabolite (o-hydroxyatorvastatin) concentrations using a validated, sensitive, and specific high-performance liquid chromatography tandem mass spectrometric method. Data presented are the result of the model used.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=15 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=24 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F)
|
553 L/hr
|
543 L/hr
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 2, Week 4, Week 6, Week 8Population: Pharmacokinetic (PK) concentration population: all enrolled and treated subjects who had ≥ 1 PK concentration assessed. Active hydroxyacid metabolite p-hydroxyatorvastatin was not included in the model as originally planned as \> 80% of samples were below detectable level at the doses used in this trial.
Parent-metabolite population PK model built using sparse blood samples from Tanner Stages 1 and 2+. Sampling times: Weeks 2 + 6: single sample between 4 -12 hours postdose; Weeks 4 + 8: predose, 1 + 2 hours postdose. Plasma samples analyzed for atorvastatin and active hydroxyacid metabolite (o-hydroxyatorvastatin) concentrations using validated, sensitive, specific high-performance liquid chromatography tandem mass spectrometric method. Vc/F value based on 70 kg body weight. Parameter estimation uncertainty (95% CI) by non-parametric bootstrap analysis. Data presented are result of model used.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=39 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Apparent Volume of Distribution of the Central Compartment (Vc/F)
|
1020 liters
Interval 209.0 to 2210.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: Pharmacodynamic (PD) analysis population: all enrolled subjects who received ≥ 1 dose of study drug and had ≥ 1 PD parameter measurement.
Low-density lipoprotein cholesterol (LDL-C) measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]). Change from baseline = value at observation minus baseline value.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Baseline
|
4.87 mmol/L
Standard Deviation 0.48
|
6.37 mmol/L
Standard Deviation 1.10
|
5.11 mmol/L
Standard Deviation 0.65
|
6.23 mmol/L
Standard Deviation 1.00
|
|
Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 2
|
-1.75 mmol/L
Standard Deviation 0.72
|
-1.62 mmol/L
Standard Deviation 0.46
|
-1.95 mmol/L
Standard Deviation 0.52
|
-1.90 mmol/L
Standard Deviation 0.72
|
|
Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 4
|
-2.07 mmol/L
Standard Deviation 0.50
|
-1.94 mmol/L
Standard Deviation 0.56
|
-2.24 mmol/L
Standard Deviation 0.57
|
-2.27 mmol/L
Standard Deviation 1.04
|
|
Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 6
|
-1.89 mmol/L
Standard Deviation 0.42
|
-2.57 mmol/L
Standard Deviation 0.70
|
-2.12 mmol/L
Standard Deviation 0.74
|
-2.55 mmol/L
Standard Deviation 1.02
|
|
Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 8
|
-1.80 mmol/L
Standard Deviation 0.63
|
-2.71 mmol/L
Standard Deviation 0.60
|
-1.99 mmol/L
Standard Deviation 0.58
|
-2.60 mmol/L
Standard Deviation 1.01
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Low-density Lipoprotein Cholesterol (LDL-C): percent (%) change from baseline by treatment over time = \[LDL-C at observation minus LDL-C at Week 0\] divided by LDL-C at Week 0 \* 100. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 2
|
-36.27 percent change in LDL-C
Standard Deviation 14.72
|
-25.70 percent change in LDL-C
Standard Deviation 7.76
|
-38.14 percent change in LDL-C
Standard Deviation 9.35
|
-30.27 percent change in LDL-C
Standard Deviation 9.22
|
|
Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 4
|
-42.33 percent change in LDL-C
Standard Deviation 8.24
|
-30.27 percent change in LDL-C
Standard Deviation 5.72
|
-43.66 percent change in LDL-C
Standard Deviation 7.78
|
-35.13 percent change in LDL-C
Standard Deviation 12.01
|
|
Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 6
|
-38.87 percent change in LDL-C
Standard Deviation 7.84
|
-40.01 percent change in LDL-C
Standard Deviation 6.34
|
-41.22 percent change in LDL-C
Standard Deviation 11.34
|
-39.73 percent change in LDL-C
Standard Deviation 10.40
|
|
Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Week 8
|
-36.78 percent change in LDL-C
Standard Deviation 11.16
|
-42.70 percent change in LDL-C
Standard Deviation 6.45
|
-38.45 percent change in LDL-C
Standard Deviation 7.84
|
-40.39 percent change in LDL-C
Standard Deviation 11.71
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Total Cholesterol measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]). Change from baseline = value at observation minus baseline value.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in Total Cholesterol (TC)
Baseline
|
6.76 mmol/L
Standard Deviation 0.46
|
8.58 mmol/L
Standard Deviation 1.06
|
6.92 mmol/L
Standard Deviation 0.71
|
8.40 mmol/L
Standard Deviation 1.10
|
|
Absolute Change From Baseline in Total Cholesterol (TC)
Week 2
|
-1.89 mmol/L
Standard Deviation 0.79
|
-2.04 mmol/L
Standard Deviation 0.69
|
-2.11 mmol/L
Standard Deviation 0.53
|
-2.28 mmol/L
Standard Deviation 0.82
|
|
Absolute Change From Baseline in Total Cholesterol (TC)
Week 4
|
-2.27 mmol/L
Standard Deviation 0.63
|
-2.24 mmol/L
Standard Deviation 0.49
|
-2.37 mmol/L
Standard Deviation 0.61
|
-2.66 mmol/L
Standard Deviation 1.29
|
|
Absolute Change From Baseline in Total Cholesterol (TC)
Week 6
|
-2.03 mmol/L
Standard Deviation 0.53
|
-2.86 mmol/L
Standard Deviation 0.79
|
-2.28 mmol/L
Standard Deviation 0.73
|
-2.95 mmol/L
Standard Deviation 1.19
|
|
Absolute Change From Baseline in Total Cholesterol (TC)
Week 8
|
-1.89 mmol/L
Standard Deviation 0.44
|
-3.20 mmol/L
Standard Deviation 0.65
|
-2.26 mmol/L
Standard Deviation 0.69
|
-3.22 mmol/L
Standard Deviation 1.14
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Total cholesterol (TC): percent (%) change from baseline by treatment over time = \[TC at observation minus TC at Week 0\] divided by TC at Week 0 \* 100. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Total Cholesterol (TC)
Week 2
|
-28.06 percent change in TC
Standard Deviation 11.23
|
-24.11 percent change in TC
Standard Deviation 8.97
|
-30.60 percent change in TC
Standard Deviation 7.49
|
-26.78 percent change in TC
Standard Deviation 7.59
|
|
Percent Change From Baseline in Total Cholesterol (TC)
Week 4
|
-33.37 percent change in TC
Standard Deviation 7.81
|
-26.12 percent change in TC
Standard Deviation 4.24
|
-33.98 percent change in TC
Standard Deviation 7.13
|
-30.54 percent change in TC
Standard Deviation 11.60
|
|
Percent Change From Baseline in Total Cholesterol (TC)
Week 6
|
-29.99 percent change in TC
Standard Deviation 8.00
|
-33.12 percent change in TC
Standard Deviation 6.83
|
-32.80 percent change in TC
Standard Deviation 8.97
|
-34.06 percent change in TC
Standard Deviation 9.94
|
|
Percent Change From Baseline in Total Cholesterol (TC)
Week 8
|
-27.80 percent change in TC
Standard Deviation 5.56
|
-37.17 percent change in TC
Standard Deviation 5.28
|
-32.43 percent change in TC
Standard Deviation 8.53
|
-37.45 percent change in TC
Standard Deviation 9.89
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Change from baseline in triglycerides measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]). Change from baseline = value at observation minus baseline value.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in Triglycerides (TG)
Baseline
|
0.76 mmol/L
Standard Deviation 0.15
|
0.95 mmol/L
Standard Deviation 0.27
|
1.03 mmol/L
Standard Deviation 0.37
|
1.20 mmol/L
Standard Deviation 0.50
|
|
Absolute Change From Baseline in Triglycerides (TG)
Week 2
|
0.05 mmol/L
Standard Deviation 0.34
|
-0.08 mmol/L
Standard Deviation 0.28
|
0.05 mmol/L
Standard Deviation 0.68
|
0.00 mmol/L
Standard Deviation 0.47
|
|
Absolute Change From Baseline in Triglycerides (TG)
Week 4
|
-0.05 mmol/L
Standard Deviation 0.29
|
-0.26 mmol/L
Standard Deviation 0.30
|
-0.10 mmol/L
Standard Deviation 0.51
|
-0.10 mmol/L
Standard Deviation 0.37
|
|
Absolute Change From Baseline in Triglycerides (TG)
Week 6
|
0.40 mmol/L
Standard Deviation 0.62
|
-0.04 mmol/L
Standard Deviation 0.24
|
-0.12 mmol/L
Standard Deviation 0.42
|
-0.04 mmol/L
Standard Deviation 0.32
|
|
Absolute Change From Baseline in Triglycerides (TG)
Week 8
|
0.02 mmol/L
Standard Deviation 0.28
|
-0.16 mmol/L
Standard Deviation 0.37
|
-0.31 mmol/L
Standard Deviation 0.43
|
-0.28 mmol/L
Standard Deviation 0.41
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Triglycerides (TG): percent (%) change from baseline by treatment over time = \[TG at observation minus TG at Week 0\] divided by TG at Week 0 \* 100. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Triglycerides (TG)
Week 2
|
5.66 percent change in TG
Standard Deviation 38.26
|
-6.87 percent change in TG
Standard Deviation 29.08
|
28.37 percent change in TG
Standard Deviation 85.32
|
-0.56 percent change in TG
Standard Deviation 32.19
|
|
Percent Change From Baseline in Triglycerides (TG)
Week 4
|
-6.20 percent change in TG
Standard Deviation 32.55
|
-21.43 percent change in TG
Standard Deviation 30.42
|
1.27 percent change in TG
Standard Deviation 50.81
|
-7.60 percent change in TG
Standard Deviation 25.75
|
|
Percent Change From Baseline in Triglycerides (TG)
Week 6
|
57.06 percent change in TG
Standard Deviation 78.73
|
-1.27 percent change in TG
Standard Deviation 23.91
|
-4.43 percent change in TG
Standard Deviation 32.52
|
-2.72 percent change in TG
Standard Deviation 24.80
|
|
Percent Change From Baseline in Triglycerides (TG)
Week 8
|
1.69 percent change in TG
Standard Deviation 31.48
|
-9.88 percent change in TG
Standard Deviation 33.31
|
-20.94 percent change in TG
Standard Deviation 39.24
|
-21.11 percent change in TG
Standard Deviation 23.85
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Change from baseline in high-density lipoprotein cholesterol measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]). Change from baseline = value at observation minus baseline value.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Baseline
|
1.35 mmol/L
Standard Deviation 0.12
|
1.45 mmol/L
Standard Deviation 0.29
|
1.17 mmol/L
Standard Deviation 0.18
|
1.18 mmol/L
Standard Deviation 0.23
|
|
Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 2
|
0.08 mmol/L
Standard Deviation 0.24
|
-0.10 mmol/L
Standard Deviation 0.29
|
-0.05 mmol/L
Standard Deviation 0.26
|
-0.01 mmol/L
Standard Deviation 0.20
|
|
Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 4
|
-0.02 mmol/L
Standard Deviation 0.05
|
0.00 mmol/L
Standard Deviation 0.19
|
0.02 mmol/L
Standard Deviation 0.21
|
-0.01 mmol/L
Standard Deviation 0.28
|
|
Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 6
|
-0.12 mmol/L
Standard Deviation 0.29
|
-0.01 mmol/L
Standard Deviation 0.18
|
0.04 mmol/L
Standard Deviation 0.14
|
-0.03 mmol/L
Standard Deviation 0.23
|
|
Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 8
|
0.04 mmol/L
Standard Deviation 0.22
|
-0.07 mmol/L
Standard Deviation 0.21
|
0.08 mmol/L
Standard Deviation 0.25
|
-0.08 mmol/L
Standard Deviation 0.22
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
High-density lipoprotein cholesterol (HDL-C): percent (%) change by treatment over time = \[HDL-C at observation minus HDL-C at Week 0\] divided by HDL-C at Week 0 \* 100. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 6
|
-10.18 percent change in HDL-C
Standard Deviation 22.70
|
-0.64 percent change in HDL-C
Standard Deviation 10.35
|
3.28 percent change in HDL-C
Standard Deviation 11.63
|
-2.78 percent change in HDL-C
Standard Deviation 21.49
|
|
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 8
|
2.50 percent change in HDL-C
Standard Deviation 15.02
|
-2.84 percent change in HDL-C
Standard Deviation 14.49
|
5.99 percent change in HDL-C
Standard Deviation 21.02
|
-5.19 percent change in HDL-C
Standard Deviation 17.76
|
|
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 2
|
5.38 percent change in HDL-C
Standard Deviation 17.32
|
-6.45 percent change in HDL-C
Standard Deviation 21.01
|
-4.11 percent change in HDL-C
Standard Deviation 19.96
|
-0.77 percent change in HDL-C
Standard Deviation 17.66
|
|
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Week 4
|
-1.99 percent change in HDL-C
Standard Deviation 3.90
|
1.59 percent change in HDL-C
Standard Deviation 13.18
|
1.04 percent change in HDL-C
Standard Deviation 17.38
|
1.77 percent change in HDL-C
Standard Deviation 23.22
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Change from baseline in Apolipoprotein A-1 measured in grams per liter (g/L); assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]). Change from baseline = value at observation minus baseline value.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Baseline
|
1.42 g/L
Standard Deviation 0.20
|
1.45 g/L
Standard Deviation 0.20
|
1.29 g/L
Standard Deviation 0.20
|
1.24 g/L
Standard Deviation 0.15
|
|
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 2
|
0.01 g/L
Standard Deviation 0.17
|
-0.08 g/L
Standard Deviation 0.23
|
-0.09 g/L
Standard Deviation 0.22
|
-0.01 g/L
Standard Deviation 0.15
|
|
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 4
|
-0.09 g/L
Standard Deviation 0.14
|
-0.06 g/L
Standard Deviation 0.13
|
-0.06 g/L
Standard Deviation 0.21
|
0.07 g/L
Standard Deviation 0.29
|
|
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 6
|
-0.14 g/L
Standard Deviation 0.18
|
-0.02 g/L
Standard Deviation 0.11
|
-0.07 g/L
Standard Deviation 0.19
|
-0.04 g/L
Standard Deviation 0.23
|
|
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 8
|
-0.03 g/L
Standard Deviation 0.12
|
-0.05 g/L
Standard Deviation 0.13
|
-0.04 g/L
Standard Deviation 0.24
|
-0.07 g/L
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Apolipoprotein A-1 (Apo A-1): percent (%) change from baseline by treatment over time = \[Apo A-1 at observation minus Apo A-1 at Week 0\] divided by Apo A-1 at Week 0 \* 100. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 8
|
-1.24 percent change in Apo A-1
Standard Deviation 8.49
|
-3.37 percent change in Apo A-1
Standard Deviation 9.35
|
-2.60 percent change in Apo A-1
Standard Deviation 20.22
|
-4.82 percent change in Apo A-1
Standard Deviation 16.13
|
|
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 2
|
1.69 percent change in Apo A-1
Standard Deviation 11.21
|
-5.24 percent change in Apo A-1
Standard Deviation 15.86
|
-5.96 percent change in Apo A-1
Standard Deviation 16.76
|
-0.53 percent change in Apo A-1
Standard Deviation 11.90
|
|
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 4
|
-5.15 percent change in Apo A-1
Standard Deviation 8.20
|
-3.30 percent change in Apo A-1
Standard Deviation 8.11
|
-3.73 percent change in Apo A-1
Standard Deviation 16.43
|
7.54 percent change in Apo A-1
Standard Deviation 25.24
|
|
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Week 6
|
-9.90 percent change in Apo A-1
Standard Deviation 14.01
|
-0.97 percent change in Apo A-1
Standard Deviation 7.04
|
-4.21 percent change in Apo A-1
Standard Deviation 14.81
|
-2.82 percent change in Apo A-1
Standard Deviation 18.20
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Change from baseline in Apolipoprotein B measured in grams per liter (g/L); assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]). Change from baseline = value at observation minus baseline value.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in Apolipoprotein B (Apo B)
Baseline
|
1.09 g/L
Standard Deviation 0.13
|
1.49 g/L
Standard Deviation 0.24
|
1.26 g/L
Standard Deviation 0.14
|
1.52 g/L
Standard Deviation 0.18
|
|
Absolute Change From Baseline in Apolipoprotein B (Apo B)
Week 2
|
-0.23 g/L
Standard Deviation 0.13
|
-0.31 g/L
Standard Deviation 0.19
|
-0.39 g/L
Standard Deviation 0.14
|
-0.42 g/L
Standard Deviation 0.16
|
|
Absolute Change From Baseline in Apolipoprotein B (Apo B)
Week 4
|
-0.33 g/L
Standard Deviation 0.11
|
-0.40 g/L
Standard Deviation 0.13
|
-0.44 g/L
Standard Deviation 0.10
|
-0.47 g/L
Standard Deviation 0.22
|
|
Absolute Change From Baseline in Apolipoprotein B (Apo B)
Week 6
|
-0.27 g/L
Standard Deviation 0.15
|
-0.53 g/L
Standard Deviation 0.17
|
-0.42 g/L
Standard Deviation 0.15
|
-0.52 g/L
Standard Deviation 0.18
|
|
Absolute Change From Baseline in Apolipoprotein B (Apo B)
Week 8
|
-0.30 g/L
Standard Deviation 0.08
|
-0.59 g/L
Standard Deviation 0.15
|
-0.41 g/L
Standard Deviation 0.17
|
-0.49 g/L
Standard Deviation 0.30
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Apolipoprotein B (Apo B): percent (%) change from baseline by treatment over time = \[Apo B at observation minus Apo B at Week 0\] divided by Apo B at Week 0 \* 100. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B (Apo B)
Week 2
|
-21.92 percent change in Apo B
Standard Deviation 13.97
|
-19.88 percent change in Apo B
Standard Deviation 10.96
|
-30.81 percent change in Apo B
Standard Deviation 10.27
|
-27.46 percent change in Apo B
Standard Deviation 8.89
|
|
Percent Change From Baseline in Apolipoprotein B (Apo B)
Week 4
|
-29.89 percent change in Apo B
Standard Deviation 8.94
|
-26.56 percent change in Apo B
Standard Deviation 5.33
|
-34.69 percent change in Apo B
Standard Deviation 6.10
|
-30.42 percent change in Apo B
Standard Deviation 11.86
|
|
Percent Change From Baseline in Apolipoprotein B (Apo B)
Week 6
|
-24.58 percent change in Apo B
Standard Deviation 12.96
|
-35.26 percent change in Apo B
Standard Deviation 6.85
|
-33.26 percent change in Apo B
Standard Deviation 10.38
|
-33.61 percent change in Apo B
Standard Deviation 9.59
|
|
Percent Change From Baseline in Apolipoprotein B (Apo B)
Week 8
|
-27.39 percent change in Apo B
Standard Deviation 5.97
|
-39.59 percent change in Apo B
Standard Deviation 5.83
|
-31.94 percent change in Apo B
Standard Deviation 11.64
|
-31.26 percent change in Apo B
Standard Deviation 18.57
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Change from baseline in very low-density lipoprotein-cholesterol (VLDL-C) measured in millimoles per liter (mmol/L). Change from baseline = value at observation minus baseline value. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 4
|
-0.18 mmol/L
Standard Deviation 0.24
|
-0.30 mmol/L
Standard Deviation 0.27
|
-0.14 mmol/L
Standard Deviation 0.24
|
-0.39 mmol/L
Standard Deviation 0.35
|
|
Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 6
|
-0.01 mmol/L
Standard Deviation 0.17
|
-0.28 mmol/L
Standard Deviation 0.32
|
-0.20 mmol/L
Standard Deviation 0.17
|
-0.36 mmol/L
Standard Deviation 0.28
|
|
Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 8
|
-0.13 mmol/L
Standard Deviation 0.32
|
-0.42 mmol/L
Standard Deviation 0.28
|
-0.35 mmol/L
Standard Deviation 0.14
|
-0.55 mmol/L
Standard Deviation 0.32
|
|
Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Baseline
|
0.54 mmol/L
Standard Deviation 0.15
|
0.76 mmol/L
Standard Deviation 0.30
|
0.65 mmol/L
Standard Deviation 0.11
|
0.99 mmol/L
Standard Deviation 0.31
|
|
Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 2
|
-0.22 mmol/L
Standard Deviation 0.12
|
-0.31 mmol/L
Standard Deviation 0.38
|
-0.12 mmol/L
Standard Deviation 0.29
|
-0.38 mmol/L
Standard Deviation 0.33
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8Population: PD analysis population
Very low-density lipoprotein-cholesterol (VLDL-C): percent (%) change from baseline by treatment over time = \[VLDL-C at observation minus VLDL-C at Week 0\] divided by VLDL-C at Week 0 \* 100. Assessments were performed in the fasting state (minimum 10-hour fast \[optional at Weeks 2 and 6\]).
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=5 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=10 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=9 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=15 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 2
|
-42.20 percent change in VLDL-C
Standard Deviation 25.17
|
-28.49 percent change in VLDL-C
Standard Deviation 43.50
|
-14.50 percent change in VLDL-C
Standard Deviation 41.19
|
-39.95 percent change in VLDL-C
Standard Deviation 37.24
|
|
Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 4
|
-30.66 percent change in VLDL-C
Standard Deviation 48.66
|
-31.86 percent change in VLDL-C
Standard Deviation 37.62
|
-21.10 percent change in VLDL-C
Standard Deviation 37.56
|
-36.35 percent change in VLDL-C
Standard Deviation 28.79
|
|
Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 6
|
4.10 percent change in VLDL-C
Standard Deviation 36.46
|
-25.59 percent change in VLDL-C
Standard Deviation 44.90
|
-29.20 percent change in VLDL-C
Standard Deviation 25.11
|
-35.08 percent change in VLDL-C
Standard Deviation 25.06
|
|
Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Week 8
|
-12.31 percent change in VLDL-C
Standard Deviation 57.38
|
-50.29 percent change in VLDL-C
Standard Deviation 21.44
|
-53.61 percent change in VLDL-C
Standard Deviation 19.21
|
-52.38 percent change in VLDL-C
Standard Deviation 29.34
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: PD analysis population. Flow-mediated dilation (FMD) was measured at centers with established FMD facilities.
Brachial artery flow-mediated dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%. Standardized image acquisition: brachial artery images recorded for one minute at rest, blood pressure cuff inflated to 250 mm Hg for 5 minutes with brachial artery imaged continuously throughout cuff inflation, cuff released to produce reactive hyperaemia and the brachial artery imaged continuously for 3 minutes after release. Total duration of measurement approximately 25 minutes. Change from baseline = value at observation minus baseline value.
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=4 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=7 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=5 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=12 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in Flow-Mediated Dilatation at Week 8
Baseline
|
4.34 FMD
Standard Deviation 3.15
|
7.41 FMD
Standard Deviation 3.30
|
5.05 FMD
Standard Deviation 3.86
|
3.67 FMD
Standard Deviation 2.51
|
|
Absolute Change From Baseline in Flow-Mediated Dilatation at Week 8
Week 8
|
-0.16 FMD
Standard Deviation 2.32
|
-1.14 FMD
Standard Deviation 1.47
|
-0.32 FMD
Standard Deviation 4.83
|
1.35 FMD
Standard Deviation 2.73
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: PD analysis population. Flow-mediated dilation (FMD) was measured at centers with established FMD facilities.
Brachial Flow-Mediated Dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%. .
Outcome measures
| Measure |
Atorvastatin (5 mg, 10 mg): Tanner Stage 1
n=4 Participants
Initial dose 5 mg/day through Week 4; after Week 4 dose may have been doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Atorvastatin (10 mg, 20 mg): Tanner Stage 2+
n=7 Participants
Initial dose 10 mg/day through Week 4; after Week 4 dose may have been doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
Stayed at 10 mg: Tanner Stage 2+
n=5 Participants
Atorvastatin 10 mg/day
|
Titrated to 20 mg: Tanner Stage 2+
n=12 Participants
Atorvastatin: initial dose 10 mg/day through Week 4; after Week 4 dose was doubled to 20 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Flow-Mediated Dilatation at Week 8
|
-17.19 percent change in FMD
Standard Deviation 23.67
|
-20.77 percent change in FMD
Standard Deviation 37.03
|
-9.77 percent change in FMD
Standard Deviation 63.20
|
1.49 percent change in FMD
Standard Deviation 28.64
|
Adverse Events
All Subjects (5 mg, 10 mg): Tanner Stage 1
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
All Subjects (10 mg, 20 mg): Tanner Stage 2+
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
All Subjects (5 mg, 10 mg): Tanner Stage 1
n=15 participants at risk
Atorvastatin: subjects who stayed at initial dose of 5 mg/day for duration of study and subjects who titrated after Week 4 to 10 mg/day if target LDL-C was not attained and study drug was well tolerated.
|
All Subjects (10 mg, 20 mg): Tanner Stage 2+
n=24 participants at risk
Atorvastatin: subjects who stayed at initial dose of 10 mg/day for duration of study and subjects who titrated to 20 mg/day after Week 4 if target LDL-C was not attained and study drug was well tolerated.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
1/15
|
0.00%
0/24
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15
|
0.00%
0/24
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/15
|
4.2%
1/24
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
1/15
|
0.00%
0/24
|
|
General disorders
Pain
|
0.00%
0/15
|
4.2%
1/24
|
|
Infections and infestations
Bronchopneumonia
|
6.7%
1/15
|
0.00%
0/24
|
|
Infections and infestations
Ear infection
|
0.00%
0/15
|
4.2%
1/24
|
|
Infections and infestations
Gastritis viral
|
6.7%
1/15
|
0.00%
0/24
|
|
Infections and infestations
Gastroenteritis
|
6.7%
1/15
|
4.2%
1/24
|
|
Infections and infestations
Influenza
|
0.00%
0/15
|
4.2%
1/24
|
|
Infections and infestations
Lower respiratory tract infection bacterial
|
0.00%
0/15
|
4.2%
1/24
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
1/15
|
8.3%
2/24
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/15
|
4.2%
1/24
|
|
Infections and infestations
Viral rhinitis
|
6.7%
1/15
|
0.00%
0/24
|
|
Infections and infestations
Viral upper respiratory tract infection
|
20.0%
3/15
|
0.00%
0/24
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/15
|
4.2%
1/24
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/15
|
8.3%
2/24
|
|
Investigations
Blood creatinine increased
|
6.7%
1/15
|
0.00%
0/24
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/15
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/15
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/15
|
4.2%
1/24
|
|
Nervous system disorders
Headache
|
13.3%
2/15
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
6.7%
1/15
|
0.00%
0/24
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/15
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.7%
1/15
|
0.00%
0/24
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER