Trial Outcomes & Findings for PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin (NCT NCT00355615)
NCT ID: NCT00355615
Last Updated: 2011-08-31
Results Overview
Percent change in low-density lipoprotein cholesterol (LDL-C) = (final value - Baseline value)/Baseline value \* 100
COMPLETED
PHASE3
173 participants
12 weeks
2011-08-31
Participant Flow
One-hundred male and female (Tanner stages II to V, at least 1 year post-menarche) children and adolescents (aged 10 to 17 years with Heterozygous familial hypercholesterolemia were randomized into the study, from 20 sites located in The United States (3 sites), The Netherlands (7 sites), Norway (1 site), Spain (3 sites), and Canada (6 sites).
Patients entered a 6 week dietary lead-in/drug washout period. Eligible patients were then randomly assigned to double-blind treatment with rosuvastatin 5 mg, 10 mg, 20 mg, or matching placebo, administered orally once daily for 12 weeks.
Participant milestones
| Measure |
Rosuva 5
rosuvastatin 5 mg
|
Rosuva 10
rosuvastatin 10 mg
|
Rosuva 20
rosuvastatin 20 mg
|
Placebo
placebo
|
Rosuva ol
rosuvastatin open label
|
|---|---|---|---|---|---|
|
Randomized Double Blind Period
STARTED
|
42
|
44
|
45
|
46
|
0
|
|
Randomized Double Blind Period
COMPLETED
|
41
|
44
|
44
|
45
|
0
|
|
Randomized Double Blind Period
NOT COMPLETED
|
1
|
0
|
1
|
1
|
0
|
|
40-week Rosuvastatin Open Label Period
STARTED
|
0
|
0
|
0
|
0
|
173
|
|
40-week Rosuvastatin Open Label Period
COMPLETED
|
0
|
0
|
0
|
0
|
164
|
|
40-week Rosuvastatin Open Label Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
9
|
Reasons for withdrawal
| Measure |
Rosuva 5
rosuvastatin 5 mg
|
Rosuva 10
rosuvastatin 10 mg
|
Rosuva 20
rosuvastatin 20 mg
|
Placebo
placebo
|
Rosuva ol
rosuvastatin open label
|
|---|---|---|---|---|---|
|
Randomized Double Blind Period
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
|
Randomized Double Blind Period
Protocol Violation
|
0
|
0
|
1
|
1
|
0
|
|
40-week Rosuvastatin Open Label Period
Adverse Event
|
0
|
0
|
0
|
0
|
4
|
|
40-week Rosuvastatin Open Label Period
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
|
40-week Rosuvastatin Open Label Period
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
3
|
|
40-week Rosuvastatin Open Label Period
investigational site closed
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
Baseline characteristics by cohort
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=45 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
Total
n=177 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
14.1 years
n=5 Participants
|
14.5 years
n=7 Participants
|
14.2 years
n=5 Participants
|
14.3 years
n=4 Participants
|
14.3 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
97 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
80 Participants
n=21 Participants
|
|
Baseline low-density lipoprotein cholesterol (LDL-C)
|
237.70 mg/dL
STANDARD_DEVIATION 55.06 • n=5 Participants
|
229.10 mg/dL
STANDARD_DEVIATION 44.70 • n=7 Participants
|
237.40 mg/dL
STANDARD_DEVIATION 47.80 • n=5 Participants
|
229.00 mg/dL
STANDARD_DEVIATION 43.13 • n=4 Participants
|
233.3 mg/dL
STANDARD_DEVIATION 10.0 • n=21 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in low-density lipoprotein cholesterol (LDL-C) = (final value - Baseline value)/Baseline value \* 100
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline (Day 0) to the End of the 12-week Double-blind Treatment Phase
|
-38.5 percentage
Standard Deviation 11.38
|
-44.4 percentage
Standard Deviation 12.15
|
-50.2 percentage
Standard Deviation 13.3
|
-0.5 percentage
Standard Deviation 13.18
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change from baseline in LDL-C after six week of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in LDL-C and Other Lipid Parameters From Baseline to Week 6, and at End of Double-blind Dose Treatment Phase (Week 12)
|
-40.3 percentage
Standard Deviation 12.22
|
-45.2 percentage
Standard Deviation 11.15
|
-50.0 percentage
Standard Deviation 11.42
|
-0.6 percentage
Standard Deviation 13.63
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent of patients achieving LDL-C \< 110 mg/dL out of the total patients in each treatment group
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Control Rate Based on Achievement of LDL-C Target of <110 mg/dL During Double-blind Dose Treatment
|
11.9 Percent of Participants
|
40.9 Percent of Participants
|
40.9 Percent of Participants
|
0.0 Percent of Participants
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in high-density lipoprotein cholesterol (HDL-C) after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in HDL-C
|
4.5 percent change
Standard Deviation 15.53
|
10.1 percent change
Standard Deviation 14.19
|
8.9 percent change
Standard Deviation 14.11
|
7.6 percent change
Standard Deviation 17.89
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in non-HDL-C at 12 weeks
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in Non-HDL-C at 12 Weeks
|
-36.3 percent change
Standard Deviation 9.98
|
-42.8 percent change
Standard Deviation 11.50
|
-47.7 percent change
Standard Deviation 13.50
|
-0.8 percent change
Standard Deviation 11.89
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in tryglycerides (TG) after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in Triglycerides (TG)
|
2.6 percent change
Standard Deviation 49.07
|
-14.2 percent change
Standard Deviation 29.66
|
-7.9 percent change
Standard Deviation 55.88
|
3.4 percent change
Standard Deviation 48.27
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change from baseline in total cholesteral after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in Total Cholesterol (TC)
|
-30.0 percent change
Standard Deviation 9.63
|
-34.1 percent change
Standard Deviation 9.5
|
-38.9 percent change
Standard Deviation 12.08
|
0.2 percent change
Standard Deviation 10.53
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in ApoA-1 after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=43 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=43 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in Apolipoprotein A-1 (ApoA-1)
|
2.3 mean percent change
Standard Deviation 9.69
|
4.3 mean percent change
Standard Deviation 9.85
|
3.9 mean percent change
Standard Deviation 10.68
|
3.6 mean percent change
Standard Deviation 15.59
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in ApoB after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=43 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=43 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in Apolipoprotein B (ApoB)
|
-32.1 mean percent change
Standard Deviation 9.13
|
-37.8 mean percent change
Standard Deviation 11.75
|
-40.7 mean percent change
Standard Deviation 13.91
|
-1.5 mean percent change
Standard Deviation 14.67
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in the ratio of ApoB/ApoA-1 after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=43 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=43 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in ApoB/ApoA-1
|
-33.1 mean percent change
Standard Deviation 9.99
|
-40.0 mean percent change
Standard Deviation 12.06
|
-42.8 mean percent change
Standard Deviation 12.23
|
-3.4 mean percent change
Standard Deviation 16.70
|
SECONDARY outcome
Timeframe: After 12 week of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in the ratio of LDL-C/HDL-C after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in LDL-C/HDL-C
|
-40.4 mean percent change
Standard Deviation 11.36
|
-48.6 mean percent change
Standard Deviation 13.26
|
-53.6 mean percent change
Standard Deviation 12.85
|
-5.5 mean percent change
Standard Deviation 17.98
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in the ratio of TC/HDL-C after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in TC/HDL-C
|
-32.1 mean percent change
Standard Deviation 10.72
|
-39.3 mean percent change
Standard Deviation 11.55
|
-43.2 mean percent change
Standard Deviation 11.76
|
-5.2 mean percent change
Standard Deviation 15.03
|
SECONDARY outcome
Timeframe: After 12 weeks of treatmentPopulation: Intention-to-treat (ITT) analysis set included all randomized patients who took study medication and had both a baseline reading and at least 1 post-baseline reading for the variable being analyzed. Analyses were performed using the last-observation-carried-forward (LOCF) method on the ITT analysis set for all efficacy outcome variables.
Percent change in the ratio of non-HDL-C/HDL-C after 12 weeks of treatment
Outcome measures
| Measure |
Rosuva 5
n=42 Participants
rosuvastatin 5 mg
|
Rosuva 10
n=44 Participants
rosuvastatin 10 mg
|
Rosuva 20
n=44 Participants
rosuvastatin 20 mg
|
Placebo
n=46 Participants
placebo
|
|---|---|---|---|---|
|
Percent Change in Non-HDL-C/HDL-C
|
-37.9 mean percent change
Standard Deviation 12.12
|
-47.1 mean percent change
Standard Deviation 13.12
|
-51.2 mean percent change
Standard Deviation 13.18
|
-5.8 mean percent change
Standard Deviation 17.63
|
Adverse Events
Rosuva 5
Rosuva 10
Rosuva 20
Placebo
Rosuva ol
Serious adverse events
| Measure |
Rosuva 5
rosuvastatin 5 mg
|
Rosuva 10
rosuvastatin 10 mg
|
Rosuva 20
rosuvastatin 20 mg
|
Placebo
placebo
|
Rosuva ol
rosuvastatin open label
|
|---|---|---|---|---|---|
|
Infections and infestations
Appendicitis
|
0.00%
0/42
|
0.00%
0/44
|
0.00%
0/44
|
0.00%
0/46
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Rash Vesicular
|
0.00%
0/42
|
0.00%
0/44
|
0.00%
0/44
|
0.00%
0/46
|
0.58%
1/173
|
|
Eye disorders
Vision Blurred
|
0.00%
0/42
|
0.00%
0/44
|
0.00%
0/44
|
2.2%
1/46
|
0.00%
0/173
|
Other adverse events
| Measure |
Rosuva 5
rosuvastatin 5 mg
|
Rosuva 10
rosuvastatin 10 mg
|
Rosuva 20
rosuvastatin 20 mg
|
Placebo
placebo
|
Rosuva ol
rosuvastatin open label
|
|---|---|---|---|---|---|
|
General disorders
Fatigue
|
2.4%
1/42
|
2.3%
1/44
|
2.3%
1/44
|
0.00%
0/46
|
5.2%
9/173
|
|
Nervous system disorders
Headache
|
14.3%
6/42
|
15.9%
7/44
|
20.5%
9/44
|
19.6%
9/46
|
16.8%
29/173
|
|
Infections and infestations
Influenza
|
4.8%
2/42
|
4.5%
2/44
|
0.00%
0/44
|
8.7%
4/46
|
8.1%
14/173
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
3/42
|
15.9%
7/44
|
15.9%
7/44
|
10.9%
5/46
|
20.8%
36/173
|
|
Gastrointestinal disorders
Nausea
|
4.8%
2/42
|
0.00%
0/44
|
4.5%
2/44
|
4.3%
2/46
|
5.8%
10/173
|
|
Gastrointestinal disorders
Tonsillitis
|
0.00%
0/42
|
0.00%
0/44
|
6.8%
3/44
|
2.2%
1/46
|
1.2%
2/173
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60