8-Week PK/PD Atorvastatin Study In Children And Adolescents With Heterozygous Familial Hypercholesterolemia
Study Details
Study Description
Brief Summary
To evaluate pharmacokinetics, pharmacodynamics, safety and tolerability of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Other: 1 6-10 years will be administered with atorvastatin tablet formulation with initial doses based on age cohort. |
Drug: Atorvastatin
6-10 years Tanner Stage 1 will be administered 5-mg daily dose of an atorvastatin pediatric tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment.
|
Other: 2 10-17 years will be administered 10-mg daily dose of atorvastatin tablet formulation. |
Drug: Atorvastatin
10-17 years Tanner Stage 2 will be administered 10-mg daily dose of atorvastatin tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment.
|
Outcome Measures
Primary Outcome Measures
- Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F) [Week 2, Week 4, Week 6, Week 8]
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.
- Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Apparent Volume of Distribution of the Central Compartment (Vc/F) [Week 2, Week 4, Week 6, Week 8]
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.
Secondary Outcome Measures
- Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) [Baseline, Week 2, Week 4, Week 6, Week 8]
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.
- Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Absolute Change From Baseline in Total Cholesterol (TC) [Baseline, Week 2, Week 4, Week 6, Week 8]
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.
- Percent Change From Baseline in Total Cholesterol (TC) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Absolute Change From Baseline in Triglycerides (TG) [Baseline, Week 2, Week 4, Week 6, Week 8]
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.
- Percent Change From Baseline in Triglycerides (TG) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) [Baseline, Week 2, Week 4, Week 6, Week 8]
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.
- Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) [Baseline, Week 2, Week 4, Week 6, Week 8]
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.
- Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Absolute Change From Baseline in Apolipoprotein B (Apo B) [Baseline, Week 2, Week 4, Week 6, Week 8]
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.
- Percent Change From Baseline in Apolipoprotein B (Apo B) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) [Baseline, Week 2, Week 4, Week 6, Week 8]
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]).
- Absolute Change From Baseline in Flow-Mediated Dilatation at Week 8 [Baseline, Week 8]
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.
- Percent Change From Baseline in Flow-Mediated Dilatation at Week 8 [Baseline, Week 8]
Brachial Flow-Mediated Dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%. .
Eligibility Criteria
Criteria
Inclusion Criteria:
- Genetically confirmed heterozygous familial hypercholesterolemia (HeFH) with LDL greater or equal 4 mmol/L at baseline
Exclusion Criteria:
- Evidence or history of clinically significant diseases, homozygous familial hypercholesterolemia (FH)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Pfizer Investigational Site | Quebec | Canada | G1V 4G2 | |
2 | Pfizer Investigational Site | Athens | Greece | 115 27 | |
3 | Pfizer Investigational Site | Oslo | Norway | 0027 |
Sponsors and Collaborators
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- A2581172
Study Results
Participant Flow
Recruitment Details | Subjects were enrolled at 3 medical centers and participated in the study between 02 December 2008 and 13 May 2009. |
---|---|
Pre-assignment Detail | Forty-five subjects were screened, and 39 subjects were assigned to study treatment. |
Arm/Group Title | Atorvastatin (5 mg, 10 mg): Tanner Stage 1 | Atorvastatin (10 mg, 20 mg): Tanner Stage 2+ |
---|---|---|
Arm/Group Description | 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. | 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. |
Period Title: Overall Study | ||
STARTED | 15 | 24 |
COMPLETED | 15 | 24 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Atorvastatin (5 mg, 10 mg): Tanner Stage 1 | Atorvastatin (10 mg, 20 mg): Tanner Stage 2+ | Total |
---|---|---|---|
Arm/Group Description | 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. | 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 of all reporting groups |
Overall Participants | 15 | 24 | 39 |
Age, Customized (participants) [Number] | |||
6-8 years |
7
46.7%
|
0
0%
|
7
17.9%
|
9-10 years |
6
40%
|
3
12.5%
|
9
23.1%
|
11-14 years |
2
13.3%
|
14
58.3%
|
16
41%
|
15-17 years |
0
0%
|
7
29.2%
|
7
17.9%
|
Sex: Female, Male (Count of Participants) | |||
Female |
7
46.7%
|
12
50%
|
19
48.7%
|
Male |
8
53.3%
|
12
50%
|
20
51.3%
|
Outcome Measures
Title | Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F) |
---|---|
Description | 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. |
Time Frame | Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Atorvastatin (5 mg, 10 mg): Tanner Stage 1 | Atorvastatin (10 mg, 20 mg): Tanner Stage 2+ |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 15 | 24 |
Number [L/hr] |
553
|
543
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Atorvastatin (5 mg, 10 mg): Tanner Stage 1, Atorvastatin (10 mg, 20 mg): Tanner Stage 2+ |
---|---|---|
Comments | Atorvastatin apparent clearance (CL/F) was described as a function of body weight using an allometric equation. The estimated parameter given is an extrapolation of the model for participants who weigh 70 kg. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Atorvastatin CL/F based on 70 kg BW |
Estimated Value | 699 | |
Confidence Interval |
(2-Sided) 95% 570 to 881 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) |
---|---|
Description | 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. |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacodynamic (PD) analysis population: all enrolled subjects who received ≥ 1 dose of study drug and had ≥ 1 PD parameter measurement. |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Baseline |
4.87
(0.48)
|
6.37
(1.10)
|
5.11
(0.65)
|
6.23
(1.00)
|
Week 2 |
-1.75
(0.72)
|
-1.62
(0.46)
|
-1.95
(0.52)
|
-1.90
(0.72)
|
Week 4 |
-2.07
(0.50)
|
-1.94
(0.56)
|
-2.24
(0.57)
|
-2.27
(1.04)
|
Week 6 |
-1.89
(0.42)
|
-2.57
(0.70)
|
-2.12
(0.74)
|
-2.55
(1.02)
|
Week 8 |
-1.80
(0.63)
|
-2.71
(0.60)
|
-1.99
(0.58)
|
-2.60
(1.01)
|
Title | Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Week 2 |
-36.27
(14.72)
|
-25.70
(7.76)
|
-38.14
(9.35)
|
-30.27
(9.22)
|
Week 4 |
-42.33
(8.24)
|
-30.27
(5.72)
|
-43.66
(7.78)
|
-35.13
(12.01)
|
Week 6 |
-38.87
(7.84)
|
-40.01
(6.34)
|
-41.22
(11.34)
|
-39.73
(10.40)
|
Week 8 |
-36.78
(11.16)
|
-42.70
(6.45)
|
-38.45
(7.84)
|
-40.39
(11.71)
|
Title | Absolute Change From Baseline in Total Cholesterol (TC) |
---|---|
Description | 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. |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Baseline |
6.76
(0.46)
|
8.58
(1.06)
|
6.92
(0.71)
|
8.40
(1.10)
|
Week 2 |
-1.89
(0.79)
|
-2.04
(0.69)
|
-2.11
(0.53)
|
-2.28
(0.82)
|
Week 4 |
-2.27
(0.63)
|
-2.24
(0.49)
|
-2.37
(0.61)
|
-2.66
(1.29)
|
Week 6 |
-2.03
(0.53)
|
-2.86
(0.79)
|
-2.28
(0.73)
|
-2.95
(1.19)
|
Week 8 |
-1.89
(0.44)
|
-3.20
(0.65)
|
-2.26
(0.69)
|
-3.22
(1.14)
|
Title | Percent Change From Baseline in Total Cholesterol (TC) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Week 2 |
-28.06
(11.23)
|
-24.11
(8.97)
|
-30.60
(7.49)
|
-26.78
(7.59)
|
Week 4 |
-33.37
(7.81)
|
-26.12
(4.24)
|
-33.98
(7.13)
|
-30.54
(11.60)
|
Week 6 |
-29.99
(8.00)
|
-33.12
(6.83)
|
-32.80
(8.97)
|
-34.06
(9.94)
|
Week 8 |
-27.80
(5.56)
|
-37.17
(5.28)
|
-32.43
(8.53)
|
-37.45
(9.89)
|
Title | Absolute Change From Baseline in Triglycerides (TG) |
---|---|
Description | 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. |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Baseline |
0.76
(0.15)
|
0.95
(0.27)
|
1.03
(0.37)
|
1.20
(0.50)
|
Week 2 |
0.05
(0.34)
|
-0.08
(0.28)
|
0.05
(0.68)
|
0.00
(0.47)
|
Week 4 |
-0.05
(0.29)
|
-0.26
(0.30)
|
-0.10
(0.51)
|
-0.10
(0.37)
|
Week 6 |
0.40
(0.62)
|
-0.04
(0.24)
|
-0.12
(0.42)
|
-0.04
(0.32)
|
Week 8 |
0.02
(0.28)
|
-0.16
(0.37)
|
-0.31
(0.43)
|
-0.28
(0.41)
|
Title | Percent Change From Baseline in Triglycerides (TG) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Week 2 |
5.66
(38.26)
|
-6.87
(29.08)
|
28.37
(85.32)
|
-0.56
(32.19)
|
Week 4 |
-6.20
(32.55)
|
-21.43
(30.42)
|
1.27
(50.81)
|
-7.60
(25.75)
|
Week 6 |
57.06
(78.73)
|
-1.27
(23.91)
|
-4.43
(32.52)
|
-2.72
(24.80)
|
Week 8 |
1.69
(31.48)
|
-9.88
(33.31)
|
-20.94
(39.24)
|
-21.11
(23.85)
|
Title | Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) |
---|---|
Description | 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. |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Baseline |
1.35
(0.12)
|
1.45
(0.29)
|
1.17
(0.18)
|
1.18
(0.23)
|
Week 2 |
0.08
(0.24)
|
-0.10
(0.29)
|
-0.05
(0.26)
|
-0.01
(0.20)
|
Week 4 |
-0.02
(0.05)
|
0.00
(0.19)
|
0.02
(0.21)
|
-0.01
(0.28)
|
Week 6 |
-0.12
(0.29)
|
-0.01
(0.18)
|
0.04
(0.14)
|
-0.03
(0.23)
|
Week 8 |
0.04
(0.22)
|
-0.07
(0.21)
|
0.08
(0.25)
|
-0.08
(0.22)
|
Title | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Week 2 |
5.38
(17.32)
|
-6.45
(21.01)
|
-4.11
(19.96)
|
-0.77
(17.66)
|
Week 4 |
-1.99
(3.90)
|
1.59
(13.18)
|
1.04
(17.38)
|
1.77
(23.22)
|
Week 6 |
-10.18
(22.70)
|
-0.64
(10.35)
|
3.28
(11.63)
|
-2.78
(21.49)
|
Week 8 |
2.50
(15.02)
|
-2.84
(14.49)
|
5.99
(21.02)
|
-5.19
(17.76)
|
Title | Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) |
---|---|
Description | 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. |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Baseline |
1.42
(0.20)
|
1.45
(0.20)
|
1.29
(0.20)
|
1.24
(0.15)
|
Week 2 |
0.01
(0.17)
|
-0.08
(0.23)
|
-0.09
(0.22)
|
-0.01
(0.15)
|
Week 4 |
-0.09
(0.14)
|
-0.06
(0.13)
|
-0.06
(0.21)
|
0.07
(0.29)
|
Week 6 |
-0.14
(0.18)
|
-0.02
(0.11)
|
-0.07
(0.19)
|
-0.04
(0.23)
|
Week 8 |
-0.03
(0.12)
|
-0.05
(0.13)
|
-0.04
(0.24)
|
-0.07
(0.21)
|
Title | Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Week 2 |
1.69
(11.21)
|
-5.24
(15.86)
|
-5.96
(16.76)
|
-0.53
(11.90)
|
Week 4 |
-5.15
(8.20)
|
-3.30
(8.11)
|
-3.73
(16.43)
|
7.54
(25.24)
|
Week 6 |
-9.90
(14.01)
|
-0.97
(7.04)
|
-4.21
(14.81)
|
-2.82
(18.20)
|
Week 8 |
-1.24
(8.49)
|
-3.37
(9.35)
|
-2.60
(20.22)
|
-4.82
(16.13)
|
Title | Absolute Change From Baseline in Apolipoprotein B (Apo B) |
---|---|
Description | 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. |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Baseline |
1.09
(0.13)
|
1.49
(0.24)
|
1.26
(0.14)
|
1.52
(0.18)
|
Week 2 |
-0.23
(0.13)
|
-0.31
(0.19)
|
-0.39
(0.14)
|
-0.42
(0.16)
|
Week 4 |
-0.33
(0.11)
|
-0.40
(0.13)
|
-0.44
(0.10)
|
-0.47
(0.22)
|
Week 6 |
-0.27
(0.15)
|
-0.53
(0.17)
|
-0.42
(0.15)
|
-0.52
(0.18)
|
Week 8 |
-0.30
(0.08)
|
-0.59
(0.15)
|
-0.41
(0.17)
|
-0.49
(0.30)
|
Title | Percent Change From Baseline in Apolipoprotein B (Apo B) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Week 2 |
-21.92
(13.97)
|
-19.88
(10.96)
|
-30.81
(10.27)
|
-27.46
(8.89)
|
Week 4 |
-29.89
(8.94)
|
-26.56
(5.33)
|
-34.69
(6.10)
|
-30.42
(11.86)
|
Week 6 |
-24.58
(12.96)
|
-35.26
(6.85)
|
-33.26
(10.38)
|
-33.61
(9.59)
|
Week 8 |
-27.39
(5.97)
|
-39.59
(5.83)
|
-31.94
(11.64)
|
-31.26
(18.57)
|
Title | Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Baseline |
0.54
(0.15)
|
0.76
(0.30)
|
0.65
(0.11)
|
0.99
(0.31)
|
Week 2 |
-0.22
(0.12)
|
-0.31
(0.38)
|
-0.12
(0.29)
|
-0.38
(0.33)
|
Week 4 |
-0.18
(0.24)
|
-0.30
(0.27)
|
-0.14
(0.24)
|
-0.39
(0.35)
|
Week 6 |
-0.01
(0.17)
|
-0.28
(0.32)
|
-0.20
(0.17)
|
-0.36
(0.28)
|
Week 8 |
-0.13
(0.32)
|
-0.42
(0.28)
|
-0.35
(0.14)
|
-0.55
(0.32)
|
Title | Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) |
---|---|
Description | 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]). |
Time Frame | Baseline, Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 5 | 10 | 9 | 15 |
Week 2 |
-42.20
(25.17)
|
-28.49
(43.50)
|
-14.50
(41.19)
|
-39.95
(37.24)
|
Week 4 |
-30.66
(48.66)
|
-31.86
(37.62)
|
-21.10
(37.56)
|
-36.35
(28.79)
|
Week 6 |
4.10
(36.46)
|
-25.59
(44.90)
|
-29.20
(25.11)
|
-35.08
(25.06)
|
Week 8 |
-12.31
(57.38)
|
-50.29
(21.44)
|
-53.61
(19.21)
|
-52.38
(29.34)
|
Title | Absolute Change From Baseline in Flow-Mediated Dilatation at Week 8 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population. Flow-mediated dilation (FMD) was measured at centers with established FMD facilities. |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 4 | 7 | 5 | 12 |
Baseline |
4.34
(3.15)
|
7.41
(3.30)
|
5.05
(3.86)
|
3.67
(2.51)
|
Week 8 |
-0.16
(2.32)
|
-1.14
(1.47)
|
-0.32
(4.83)
|
1.35
(2.73)
|
Title | Percent Change From Baseline in Flow-Mediated Dilatation at Week 8 |
---|---|
Description | Brachial Flow-Mediated Dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%. . |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
PD analysis population. Flow-mediated dilation (FMD) was measured at centers with established FMD facilities. |
Arm/Group Title | Stayed at 5 mg: Tanner Stage 1 | Titrated to 10 mg: Tanner Stage 1 | Stayed at 10 mg: Tanner Stage 2+ | Titrated to 20 mg: Tanner Stage 2+ |
---|---|---|---|---|
Arm/Group Description | Atorvastatin 5 mg/day | Atorvastatin: initial dose 5 mg/day through Week 4; after Week 4 dose was doubled to 10 mg/day if target LDL-C was not attained and study drug was well tolerated. | Atorvastatin 10 mg/day | 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. |
Measure Participants | 4 | 7 | 5 | 12 |
Mean (Standard Deviation) [percent change in FMD] |
-17.19
(23.67)
|
-20.77
(37.03)
|
-9.77
(63.20)
|
1.49
(28.64)
|
Title | Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Apparent Volume of Distribution of the Central Compartment (Vc/F) |
---|---|
Description | 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. |
Time Frame | Week 2, Week 4, Week 6, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Atorvastatin (5 mg, 10 mg, 20 mg): Tanner Stages 1 and 2+ |
---|---|
Arm/Group Description | 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 LDL-C was not attained and study drug was well tolerated; 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. |
Measure Participants | 39 |
Number (95% Confidence Interval) [liters] |
1020
|
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | All Subjects (5 mg, 10 mg): Tanner Stage 1 | All Subjects (10 mg, 20 mg): Tanner Stage 2+ | ||
Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
All Subjects (5 mg, 10 mg): Tanner Stage 1 | All Subjects (10 mg, 20 mg): Tanner Stage 2+ | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
All Subjects (5 mg, 10 mg): Tanner Stage 1 | All Subjects (10 mg, 20 mg): Tanner Stage 2+ | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/15 (0%) | 0/24 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
All Subjects (5 mg, 10 mg): Tanner Stage 1 | All Subjects (10 mg, 20 mg): Tanner Stage 2+ | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 9/15 (60%) | 13/24 (54.2%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 1/15 (6.7%) | 0/24 (0%) | ||
Nausea | 1/15 (6.7%) | 0/24 (0%) | ||
Toothache | 0/15 (0%) | 1/24 (4.2%) | ||
Vomiting | 1/15 (6.7%) | 0/24 (0%) | ||
General disorders | ||||
Pain | 0/15 (0%) | 1/24 (4.2%) | ||
Infections and infestations | ||||
Bronchopneumonia | 1/15 (6.7%) | 0/24 (0%) | ||
Ear infection | 0/15 (0%) | 1/24 (4.2%) | ||
Gastritis viral | 1/15 (6.7%) | 0/24 (0%) | ||
Gastroenteritis | 1/15 (6.7%) | 1/24 (4.2%) | ||
Influenza | 0/15 (0%) | 1/24 (4.2%) | ||
Lower respiratory tract infection bacterial | 0/15 (0%) | 1/24 (4.2%) | ||
Nasopharyngitis | 1/15 (6.7%) | 2/24 (8.3%) | ||
Tonsillitis | 0/15 (0%) | 1/24 (4.2%) | ||
Viral rhinitis | 1/15 (6.7%) | 0/24 (0%) | ||
Viral upper respiratory tract infection | 3/15 (20%) | 0/24 (0%) | ||
Injury, poisoning and procedural complications | ||||
Hand fracture | 0/15 (0%) | 1/24 (4.2%) | ||
Investigations | ||||
Alanine aminotransferase increased | 0/15 (0%) | 2/24 (8.3%) | ||
Blood creatinine increased | 1/15 (6.7%) | 0/24 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 0/15 (0%) | 1/24 (4.2%) | ||
Musculoskeletal pain | 0/15 (0%) | 1/24 (4.2%) | ||
Pain in extremity | 0/15 (0%) | 1/24 (4.2%) | ||
Nervous system disorders | ||||
Headache | 2/15 (13.3%) | 1/24 (4.2%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Asthma | 1/15 (6.7%) | 0/24 (0%) | ||
Rhinitis allergic | 0/15 (0%) | 1/24 (4.2%) | ||
Skin and subcutaneous tissue disorders | ||||
Urticaria | 1/15 (6.7%) | 0/24 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Pfizer ClinicalTrials.gov Call Center |
---|---|
Organization | Pfizer, Inc. |
Phone | 1-800-718-1021 |
ClinicalTrials.govCallCenter@pfizer.com |
- A2581172