Familial Hypercholesterolemia
Conditions
Keywords
Heterozygous Familial Hypercholesterolemia
Brief summary
The primary objective of this study is to determine the efficacy of once-daily rosuvastatin in reducing LDL-C in children and adolescents aged 10-17 years with HeFH from baseline (Day 0) to the end of the 12-week double-blind treatment period.
Interventions
DRUGRosuvastatin
oral
DRUGPlacebo
oral
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female (at least 1 year post-menarche) children and adolescents (aged 10 -17 years) with heterozygous familial hypercholesterolemia (HeFH)
Exclusion criteria
* Certain medical conditions and lab test results * History of a reaction to rosuvastatin or other statin drugs * Use of specified disallowed medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline (Day 0) to the End of the 12-week Double-blind Treatment Phase | 12 weeks | Percent change in low-density lipoprotein cholesterol (LDL-C) = (final value - Baseline value)/Baseline value \* 100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Control Rate Based on Achievement of LDL-C Target of <110 mg/dL During Double-blind Dose Treatment | 12 weeks | Percent of patients achieving LDL-C \< 110 mg/dL out of the total patients in each treatment group |
| Percent Change in HDL-C | After 12 weeks of treatment | Percent change in high-density lipoprotein cholesterol (HDL-C) after 12 weeks of treatment |
| Percent Change in Non-HDL-C at 12 Weeks | After 12 weeks of treatment | Percent change in non-HDL-C at 12 weeks |
| Percent Change in Triglycerides (TG) | After 12 weeks of treatment | Percent change in tryglycerides (TG) after 12 weeks of treatment |
| Percent Change in Total Cholesterol (TC) | After 12 weeks of treatment | Percent change from baseline in total cholesteral after 12 weeks of treatment |
| 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) | 6 weeks | Percent change from baseline in LDL-C after six week of treatment |
| Percent Change in Apolipoprotein B (ApoB) | After 12 weeks of treatment | Percent change in ApoB after 12 weeks of treatment |
| Percent Change in ApoB/ApoA-1 | After 12 weeks of treatment | Percent change in the ratio of ApoB/ApoA-1 after 12 weeks of treatment |
| Percent Change in LDL-C/HDL-C | After 12 week of treatment | Percent change in the ratio of LDL-C/HDL-C after 12 weeks of treatment |
| Percent Change in TC/HDL-C | After 12 weeks of treatment | Percent change in the ratio of TC/HDL-C after 12 weeks of treatment |
| Percent Change in Non-HDL-C/HDL-C | After 12 weeks of treatment | Percent change in the ratio of non-HDL-C/HDL-C after 12 weeks of treatment |
| Percent Change in Apolipoprotein A-1 (ApoA-1) | After 12 weeks of treatment | Percent change in ApoA-1 after 12 weeks of treatment |
Countries
Canada, Netherlands, Norway, Spain, United States
Participant flow
Recruitment details
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).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Rosuva 5 rosuvastatin 5 mg | 42 |
| Rosuva 10 rosuvastatin 10 mg | 44 |
| Rosuva 20 rosuvastatin 20 mg | 45 |
| Placebo placebo | 46 |
| Total | 177 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| 40-week Rosuvastatin Open Label Period | Adverse Event | 0 | 0 | 0 | 0 | 4 |
| 40-week Rosuvastatin Open Label Period | investigational site closed | 0 | 0 | 0 | 0 | 1 |
| 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 |
| Randomized Double Blind Period | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Randomized Double Blind Period | Protocol Violation | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Rosuva 5 | Rosuva 10 | Rosuva 20 | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 14.1 years | 14.5 years | 14.2 years | 14.3 years | 14.3 years |
| Baseline low-density lipoprotein cholesterol (LDL-C) | 237.70 mg/dL STANDARD_DEVIATION 55.06 | 229.10 mg/dL STANDARD_DEVIATION 44.7 | 237.40 mg/dL STANDARD_DEVIATION 47.8 | 229.00 mg/dL STANDARD_DEVIATION 43.13 | 233.3 mg/dL STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 26 Participants | 25 Participants | 22 Participants | 24 Participants | 97 Participants |
| Sex: Female, Male Male | 16 Participants | 19 Participants | 23 Participants | 22 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / — | 14 / — | 17 / — | 17 / — | 75 / — |
| serious Total, serious adverse events | 0 / — | 0 / — | 0 / — | 1 / — | 2 / — |
Outcome results
Primary
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline (Day 0) to the End of the 12-week Double-blind Treatment Phase
Percent change in low-density lipoprotein cholesterol (LDL-C) = (final value - Baseline value)/Baseline value \* 100
Time frame: 12 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | 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 |
| Rosuva 10 | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline (Day 0) to the End of the 12-week Double-blind Treatment Phase | -44.4 percentage | Standard Deviation 12.15 |
| Rosuva 20 | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline (Day 0) to the End of the 12-week Double-blind Treatment Phase | -50.2 percentage | Standard Deviation 13.3 |
| 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 | -0.5 percentage | Standard Deviation 13.18 |
Secondary
Percent Change in ApoB/ApoA-1
Percent change in the ratio of ApoB/ApoA-1 after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in ApoB/ApoA-1 | -33.1 mean percent change | Standard Deviation 9.99 |
| Rosuva 10 | Percent Change in ApoB/ApoA-1 | -40.0 mean percent change | Standard Deviation 12.06 |
| Rosuva 20 | Percent Change in ApoB/ApoA-1 | -42.8 mean percent change | Standard Deviation 12.23 |
| Placebo | Percent Change in ApoB/ApoA-1 | -3.4 mean percent change | Standard Deviation 16.7 |
Secondary
Percent Change in Apolipoprotein A-1 (ApoA-1)
Percent change in ApoA-1 after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in Apolipoprotein A-1 (ApoA-1) | 2.3 mean percent change | Standard Deviation 9.69 |
| Rosuva 10 | Percent Change in Apolipoprotein A-1 (ApoA-1) | 4.3 mean percent change | Standard Deviation 9.85 |
| Rosuva 20 | Percent Change in Apolipoprotein A-1 (ApoA-1) | 3.9 mean percent change | Standard Deviation 10.68 |
| Placebo | Percent Change in Apolipoprotein A-1 (ApoA-1) | 3.6 mean percent change | Standard Deviation 15.59 |
Secondary
Percent Change in Apolipoprotein B (ApoB)
Percent change in ApoB after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in Apolipoprotein B (ApoB) | -32.1 mean percent change | Standard Deviation 9.13 |
| Rosuva 10 | Percent Change in Apolipoprotein B (ApoB) | -37.8 mean percent change | Standard Deviation 11.75 |
| Rosuva 20 | Percent Change in Apolipoprotein B (ApoB) | -40.7 mean percent change | Standard Deviation 13.91 |
| Placebo | Percent Change in Apolipoprotein B (ApoB) | -1.5 mean percent change | Standard Deviation 14.67 |
Secondary
Percent Change in HDL-C
Percent change in high-density lipoprotein cholesterol (HDL-C) after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in HDL-C | 4.5 percent change | Standard Deviation 15.53 |
| Rosuva 10 | Percent Change in HDL-C | 10.1 percent change | Standard Deviation 14.19 |
| Rosuva 20 | Percent Change in HDL-C | 8.9 percent change | Standard Deviation 14.11 |
| Placebo | Percent Change in HDL-C | 7.6 percent change | Standard Deviation 17.89 |
Secondary
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)
Percent change from baseline in LDL-C after six week of treatment
Time frame: 6 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | 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 |
| Rosuva 10 | 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) | -45.2 percentage | Standard Deviation 11.15 |
| Rosuva 20 | 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) | -50.0 percentage | Standard Deviation 11.42 |
| 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) | -0.6 percentage | Standard Deviation 13.63 |
Secondary
Percent Change in LDL-C/HDL-C
Percent change in the ratio of LDL-C/HDL-C after 12 weeks of treatment
Time frame: After 12 week of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in LDL-C/HDL-C | -40.4 mean percent change | Standard Deviation 11.36 |
| Rosuva 10 | Percent Change in LDL-C/HDL-C | -48.6 mean percent change | Standard Deviation 13.26 |
| Rosuva 20 | Percent Change in LDL-C/HDL-C | -53.6 mean percent change | Standard Deviation 12.85 |
| Placebo | Percent Change in LDL-C/HDL-C | -5.5 mean percent change | Standard Deviation 17.98 |
Secondary
Percent Change in Non-HDL-C at 12 Weeks
Percent change in non-HDL-C at 12 weeks
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in Non-HDL-C at 12 Weeks | -36.3 percent change | Standard Deviation 9.98 |
| Rosuva 10 | Percent Change in Non-HDL-C at 12 Weeks | -42.8 percent change | Standard Deviation 11.5 |
| Rosuva 20 | Percent Change in Non-HDL-C at 12 Weeks | -47.7 percent change | Standard Deviation 13.5 |
| Placebo | Percent Change in Non-HDL-C at 12 Weeks | -0.8 percent change | Standard Deviation 11.89 |
Secondary
Percent Change in Non-HDL-C/HDL-C
Percent change in the ratio of non-HDL-C/HDL-C after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in Non-HDL-C/HDL-C | -37.9 mean percent change | Standard Deviation 12.12 |
| Rosuva 10 | Percent Change in Non-HDL-C/HDL-C | -47.1 mean percent change | Standard Deviation 13.12 |
| Rosuva 20 | Percent Change in Non-HDL-C/HDL-C | -51.2 mean percent change | Standard Deviation 13.18 |
| Placebo | Percent Change in Non-HDL-C/HDL-C | -5.8 mean percent change | Standard Deviation 17.63 |
Secondary
Percent Change in TC/HDL-C
Percent change in the ratio of TC/HDL-C after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in TC/HDL-C | -32.1 mean percent change | Standard Deviation 10.72 |
| Rosuva 10 | Percent Change in TC/HDL-C | -39.3 mean percent change | Standard Deviation 11.55 |
| Rosuva 20 | Percent Change in TC/HDL-C | -43.2 mean percent change | Standard Deviation 11.76 |
| Placebo | Percent Change in TC/HDL-C | -5.2 mean percent change | Standard Deviation 15.03 |
Secondary
Percent Change in Total Cholesterol (TC)
Percent change from baseline in total cholesteral after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in Total Cholesterol (TC) | -30.0 percent change | Standard Deviation 9.63 |
| Rosuva 10 | Percent Change in Total Cholesterol (TC) | -34.1 percent change | Standard Deviation 9.5 |
| Rosuva 20 | Percent Change in Total Cholesterol (TC) | -38.9 percent change | Standard Deviation 12.08 |
| Placebo | Percent Change in Total Cholesterol (TC) | 0.2 percent change | Standard Deviation 10.53 |
Secondary
Percent Change in Triglycerides (TG)
Percent change in tryglycerides (TG) after 12 weeks of treatment
Time frame: After 12 weeks of treatment
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuva 5 | Percent Change in Triglycerides (TG) | 2.6 percent change | Standard Deviation 49.07 |
| Rosuva 10 | Percent Change in Triglycerides (TG) | -14.2 percent change | Standard Deviation 29.66 |
| Rosuva 20 | Percent Change in Triglycerides (TG) | -7.9 percent change | Standard Deviation 55.88 |
| Placebo | Percent Change in Triglycerides (TG) | 3.4 percent change | Standard Deviation 48.27 |
Secondary
Percent Control Rate Based on Achievement of LDL-C Target of <110 mg/dL During Double-blind Dose Treatment
Percent of patients achieving LDL-C \< 110 mg/dL out of the total patients in each treatment group
Time frame: 12 weeks
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rosuva 5 | Percent Control Rate Based on Achievement of LDL-C Target of <110 mg/dL During Double-blind Dose Treatment | 11.9 Percent of Participants |
| Rosuva 10 | Percent Control Rate Based on Achievement of LDL-C Target of <110 mg/dL During Double-blind Dose Treatment | 40.9 Percent of Participants |
| Rosuva 20 | Percent Control Rate Based on Achievement of LDL-C Target of <110 mg/dL During Double-blind Dose Treatment | 40.9 Percent of Participants |
| Placebo | Percent Control Rate Based on Achievement of LDL-C Target of <110 mg/dL During Double-blind Dose Treatment | 0.0 Percent of Participants |