HYDRA: A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02226198
• Collaborator: (none)
• Enrollment: 20
• Locations: 9
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of the study is to establish the efficacy, safety and tolerability of rosuvastatin in children and adolescents with homozygous familial hypercholesterolemia.

Condition or Disease	Intervention/Treatment	Phase
Homozygous Familial Hypercholesterolemia (HoFH)	Drug: Rosuvastatin 20mg; Drug: Placebo	Phase 3

Detailed Description

This is a randomized, double-blind, placebo-controlled, multi-center, cross-over study of the efficacy, safety and tolerability rosuvastatin in children and adolescents (aged 6 to <18 years) with homozygous familial hypercholesterolemia (HoFH). The study is designed to assess the efficacy of rosuvastatin 20 mg compared to placebo on lipids, lipoproteins and apolipoproteins in pediatric patients with HoFH. The outcome measures to be assessed include low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides, non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, apolipoprotein B (ApoB), apolipoprotein A 1 (ApoA-1) and ApoB/ApoA-1 following 6 weeks of treatment with rosuvastatin 20 mg or placebo. Pharmacokinetic data of the trough plasma exposure of rosuvastatin will also be assessed in these pediatric patients with HoFH.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multi-center, Cross-over Study of Rosuvastatin in Children and Adolescents (Aged 6 to <18 Years) With Homozygous Familial Hypercholesterolemia (HoFH)
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rosuvastatin 6-week treatment period, and after crossover finished a 12-week efficacy maintenance phase for all patients	Drug: Rosuvastatin 20mg; Active drug will be taken taken orally, QD, either in the morning or in the evening
Placebo Comparator: Placebo 6 weeks treatment during crossover	Drug: Placebo; Will be taken taken orally, QD, either in the morning or in the evening

Outcome Measures

Primary Outcome Measures

1. LDL-Cholesterol (mg/dL) [Samples taken on Day 42 (week 6) and on day 84 (week 12)]

   Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment

2. LDL-Cholesterol (mmol/L) [Samples taken on Day 42 (week 6) and on day 84 (week 12)]

   Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment

Secondary Outcome Measures

1. TC (mg/dL) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of total cholesterol (TC)

2. TC (mmol/L) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of total cholesterol (TC)

3. Non-HDL C (mg/dL) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)

4. Non-HDL C (mmol/L) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)

5. ApoB (mg/dL) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of apolipoprotein B (ApoB)

6. ApoB (g/L) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of apolipoprotein B (ApoB)

7. HDL-C (mg/dL) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of high density lipoprotein cholesterol (HDL C)

8. HDL-C (mmol/L) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of high density lipoprotein cholesterol (HDL C)

9. LDL-C, Not on Apheresis (mg/dL) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

   Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis

10. LDL-C, Not on Apheresis (mmol/L) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis

11. LDL-C From End of Placebo (mg/dL) [Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)]

    Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg

12. LDL-C From End of Placebo (mmol/L) [Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)]

    Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg

13. Trough Concentrations [Samples taken 24 hours post-dose at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18)]

    Pharmacokinetic profile in terms of trough concentrations. Cross-over phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the cross-over phase. Maintenance phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the maintenance phase.

14. Adverse Events [From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

    Safety and tolerability will be described in terms of frequency and severity of adverse events

15. AE's Leading to Discontinuation [From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

    Safety and tolerability will be described in terms of rate of discontinuations due to adverse events

16. Abnormal Serum Levels [From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

    Safety and tolerability will be described in terms of abnormal serum laboratory values. The reported parameters are not the only ones measured, but rather those for which abnormailities were found

17. Height [Week 0 (start of cross-over), weeks 6, week 12 and week 18]

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

18. Height Z-score [Week 0 (start of cross-over), weeks 6, week 12 and week 18]

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

19. Weight [Week 0 (start of cross-over), weeks 6, week 12 and week 18]

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

20. Tanner Stage [Week 0 (start of cross-over)]

    Stages for fem (Pubic hair, Breasts): (Preadol,Preadol) (Sparse, lightly pigmented, medial border of labia,Breast and papilla elevated as small mound; areolar diam incr) (Darker, beginning to curl, incr amount, Breast and areola enlarged, no contour separation) (Course, curly, abundant but less amount in adult,Areola and papilla form secondary mound) (Adult fem triangle, spread to medial surface of thighs,Mature, nipple projects, areola part of general breast contour) For males (Pubic hair, Penis, Testes) 1=(None,Preadol,Preadol) 2=(Scanty, long, light pigm,Slight enl,Enl scrotum, pink texture alt) 3=(Darker, starts to curl, small amount,Longer,Larger) 4=(Resembles adult type, but less in quant; course, curly,Larger; glans and breadth increased in size,Larger, scrotum dark) 5=(Adult distr, spread to medial thighs,Adult size,Adult size). Progr at a normal rate is preferred. Regr is not preferred.

21. TG (mg/dL) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

    Efficacy in terms of triglycerides (TG)

22. TG (mmol/L) [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

    Efficacy in terms of triglycerides (TG)

23. LDL C/HDL C [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) / high density lipoprotein cholesterol (HDL C)

24. TC/HDL C [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

    Efficacy in terms of total cholesterol (TC) / high density lipoprotein cholesterol (HDL C)

25. Non-HDL C/HDL C [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

    Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C) / HDL C

26. ApoB/ApoA [Samples taken at Day 42 (week 6) and Day 84 (week 12)]

    Efficacy in terms of apolipoprotein B (ApoB) / apolipoprotein A (ApoA)

27. Urinalysis Abnormalitites [Week 0, week 6, week 12 and week 18]

    Safety and tolerability will be described in terms of abnormal urine laboratory values

28. ECG Abnormalities [Week 0]

    Safety and tolerability will be described in terms of abnormal electro cardio gram (ECG)

29. Physical Exam Abnormalitites [Screening, Week 0, week 6, week 12 and week 18, week 24]

    Safety and tolerability will be described in terms of abnormal physical examinations. Only parameters for which abnormalities were found are reported.

30. Abnormal Vital Signs [From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

    Safety and tolerability will be described in terms of abnormal vital signs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Prior to any study related procedures being performed, provision of written informed consent from a parent/both parents or guardian and statement of assent from the child or adolescent (if required by Institutional Review Board [IRB] or Independent Ethics Committee [EC] according to local regulations and guidelines). Communication between the Investigator, patient/guardian and child/adolescent to confirm understanding and required compliance with the requirements of the study.

2. Male and female children and adolescents (aged 6 to <18 years) with at least 1 of the following criteria:

Documentation of genetic testing confirming 2 mutated alleles of the LDL receptor gene locus; and/or

Documented untreated LDL C >500 mg/dL (12.9 mmol/L) and triglyceride (TG) <300 mg/dL (3.4 mmol/L) and at least 1 of the following criteria:

1. Tendinous and/or cutaneous xanthoma prior to 10 years of age; or

2. Documentation of HoFH in both parents by:

• genetic and/or

• clinical criteria

1. Negative pregnancy test (b human chorionic gonadotropin analysis) prior to baseline in females of child bearing potential:

• Female patients of child bearing potential must adhere to a pregnancy prevention method (abstinence, chemical, or mechanical) during the study and 3 months following the last dose.

• Male patients should refrain from fathering a child (including sperm donation) during the study and up to 3 months following the last dose; and

1. Willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.

Exclusion Criteria

1. History of statin inducted myopathy or serious hypersensitivity reaction to other HMG CoA reductase inhibitors (statins), including rosuvastatin, at Visit 1.

2. Fasting serum glucose of >9.99 mmol/L (180 mg/dL) or glycosylated hemoglobin >9% at Visit 1 or patients with a history of diabetic ketoacidosis within the past year.

3. Uncontrolled hypothyroidism defined as thyroid stimulating hormone (TSH) >1.5 times the upper limit of normal (ULN) at Visit 1 or patients whose thyroid replacement therapy was initiated or modified within the last 3 months prior to Visit 2.

4. Current active liver disease or hepatic dysfunction (except a confirmed diagnosis of Gilbert's disease) as defined as elevations of 1.5 times the upper limit of normal (ULN) for any age in any of the following liver function tests at Visit 1: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or bilirubin.

5. Definite or suspected personal history or family history of clinically significant adverse drug reactions (ADRs), or hypersensitivity to drugs with a similar chemical structure to rosuvastatin as well as other statins.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Brussels (Woluwé-St-Lambert)		Belgium
2	Research Site	Chicoutimi	Quebec	Canada
3	Research Site	København Ø		Denmark
4	Research Site	Haifa		Israel
5	Research Site	Kuala Lumpur		Malaysia
6	Research Site	Kubang Kerian		Malaysia
7	Research Site	Amsterdam		Netherlands
8	Research Site	Goteborg		Netherlands
9	Research Site	Taipei		Taiwan

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02226198
• Other Study ID Numbers: D3561C00004
• First Posted: Aug 27, 2014
• Last Update Posted: Jul 4, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by AstraZeneca: LDL-C; HoFH; Hyperlipidemia
• Additional relevant MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia; Rosuvastatin Calcium

Study Results

Participant Flow

Recruitment Details	Twenty HoFH patients were recruited to 9 centers within 8 countries (Belgium, Canada, Denmark, Israel, Malaysia, Sweden, Taiwan, and The Netherlands) that participated in the study. FSI date: 03-Nov-2014
Pre-assignment Detail	20 enrolled, 3 withdrew consent, 3 did not fulfil eligibility criteria. Among the 14 left, ten went through 4 week lead-in phase and 4 did not.

Arm/Group Title	Overall	Rosuva First Then Placebo	Placebo First Then Rosuva
Arm/Group Description	Relevant for the lead-in and maintenance phases	Relevant for the cross-over phase	Relevant for the cross-over phase
Period Title: Lead-in Phase
STARTED	11	0	0
COMPLETED	10	0	0
NOT COMPLETED	1	0	0
Period Title: Lead-in Phase
STARTED	0	7	7
COMPLETED	0	6	7
NOT COMPLETED	0	1	0
Period Title: Lead-in Phase
STARTED	0	6	7
COMPLETED	0	6	7
NOT COMPLETED	0	0	0
Period Title: Lead-in Phase
STARTED	13	0	0
COMPLETED	13	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Cross-over
Arm/Group Description	Cross-over phase
Overall Participants	14
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	10.9 (2.70)
Sex: Female, Male (Count of Participants)
Female	7 50%
Male	7 50%

Outcome Measures

1. Primary Outcome

Title	LDL-Cholesterol (mg/dL)
Description	Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment
Time Frame	Samples taken on Day 42 (week 6) and on day 84 (week 12)

Outcome Measure Data

Analysis Population Description

6-17 years HoFH

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mg/dL]	396.0 (195.99)	481.4 (184.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc. Powered for 90% detection of 15% delta
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-22.3
	Confidence Interval	(2-Sided) 95%; -33.5 to -9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Rosuvastatin treatment gives on average a 22.3% lower geometric LS mean than placebo.

2. Primary Outcome

Title	LDL-Cholesterol (mmol/L)
Description	Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment
Time Frame	Samples taken on Day 42 (week 6) and on day 84 (week 12)

Outcome Measure Data

Analysis Population Description

6-17 years HoFH

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mmol/L]	10.26 (5.076)	12.47 (4.790)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc. Powered for 90% detection of 15% delta
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-22.3
	Confidence Interval	(2-Sided) 95%; -33.5 to -9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Rosuvastatin treatment gives on average a 22.3% lower geometric LS mean than placebo.

3. Secondary Outcome

Title	TC (mg/dL)
Description	Efficacy in terms of total cholesterol (TC)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mg/dL]	447.6 (195.46)	539.0 (184.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-20.1
	Confidence Interval	(2-Sided) 95%; -29.7 to -9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	TC (mmol/L)
Description	Efficacy in terms of total cholesterol (TC)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mmol/L]	11.59 (5.063)	13.96 (4.790)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-20.1
	Confidence Interval	(2-Sided) 95%; -29.7 to -9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Non-HDL C (mg/dL)
Description	Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mg/dL]	412.1 (198.62)	505.3 (186.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-22.9
	Confidence Interval	(2-Sided) 95%; -33.7 to -10.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Non-HDL C (mmol/L)
Description	Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mmol/L]	10.67 (5.144)	13.09 (4.826)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-22.9
	Confidence Interval	(2-Sided) 95%; -33.7 to -10.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	ApoB (mg/dL)
Description	Efficacy in terms of apolipoprotein B (ApoB)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mg/dL]	234.9 (107.02)	267.9 (86.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-17.1
	Confidence Interval	(2-Sided) 95%; -29.2 to -2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	ApoB (g/L)
Description	Efficacy in terms of apolipoprotein B (ApoB)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [g/L]	2.35 (1.070)	2.68 (0.863)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-17.1
	Confidence Interval	(2-Sided) 95%; -29.2 to -2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	HDL-C (mg/dL)
Description	Efficacy in terms of high density lipoprotein cholesterol (HDL C)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mg/dL]	35.5 (7.29)	33.7 (8.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	7.4
	Confidence Interval	(2-Sided) 95%; -7.4 to 24.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	HDL-C (mmol/L)
Description	Efficacy in terms of high density lipoprotein cholesterol (HDL C)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mmol/L]	0.92 (0.189)	0.87 (0.218)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	7.4
	Confidence Interval	(2-Sided) 95%; -7.4 to 24.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	LDL-C, Not on Apheresis (mg/dL)
Description	Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

Patients not treated with apheresis

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	6	6
Mean (Standard Deviation) [mg/dL]	479.8 (239.07)	594.7 (203.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-26.3
	Confidence Interval	(2-Sided) 95%; -48.7 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	LDL-C, Not on Apheresis (mmol/L)
Description	Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

Patients not treated with apheresis

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo Not on Apheresis
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	6	6
Mean (Standard Deviation) [mmol/L]	12.43 (6.191)	15.40 (5.274)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-26.3
	Confidence Interval	(2-Sided) 95%; -48.7 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	LDL-C From End of Placebo (mg/dL)
Description	Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg
Time Frame	Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	M-FAS Rosuvastatin	M-FAS Placebo
Arm/Group Description	Maintenance Full Analysis Set, starting cross-over phase with 6 weeks of rosuvastatin	Maintenance Full Analysis Set, starting cross-over phase with 6 weeks of placebo
Measure Participants	7	6
End of Placebo	472.9 (171.77)	491.3 (215.46)
6 weeks after end of Placebo	399.4 (214.28)	421.7 (224.49)
12 weeks after end of Placebo	345.8 (214.69)	394.7 (178.45)
18 weeks after end of Placebo	NA (NA)	441.8 (260.31)

14. Secondary Outcome

Title	LDL-C From End of Placebo (mmol/L)
Description	Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg
Time Frame	Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	M-FAS Rosuvastatin	M-FAS Placebo
Arm/Group Description	Maintenance Full Analysis Set, starting cross-over phase with 6 weeks of rosuvastatin	Maintenance Full Analysis Set, starting cross-over phase with 6 weeks of placebo
Measure Participants	7	6
End of Placebo	12.25 (4.449)	12.73 (5.583)
6 weeks after end of Placebo	10.34 (5.551)	10.92 (5.813)
12 weeks after end of Placebo	8.96 (5.558)	10.22 (4.621)
18 weeks after end of Placebo	NA (NA)	11.44 (6.740)

15. Secondary Outcome

Title	Trough Concentrations
Description	Pharmacokinetic profile in terms of trough concentrations. Cross-over phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the cross-over phase. Maintenance phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the maintenance phase.
Time Frame	Samples taken 24 hours post-dose at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cross-over Phase	Maintenance Phase
Arm/Group Description	Measurements taken after 6 weeks active treatment (rosuvastatin) in the cross-over phase	Measurement taken after 6 weeks active treatment (rosuvastatin) in the maintenance phase.
Measure Participants	11	13
Mean (Standard Deviation) [ng/mL]	7.387 (8.11)	4.482 (3.50)

16. Secondary Outcome

Title	Adverse Events
Description	Safety and tolerability will be described in terms of frequency and severity of adverse events
Time Frame	From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lead-in	Cross-over Phase	Maintenance
Arm/Group Description	Optional 10mg lead-in phase, Safety analysis set	Cross-over phase, Safety analysis set	Maintenance Phase, Safety analysis set
Measure Participants	11	14	13
Any AE	4	5	1
Any TEAE	4	5	1
Any AE leading to death	0	0	0
Any SAE	0	0	0

17. Secondary Outcome

Title	AE's Leading to Discontinuation
Description	Safety and tolerability will be described in terms of rate of discontinuations due to adverse events
Time Frame	From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lead-in	Cross-over Phase	Maintenance Phase
Arm/Group Description	Optional 10mg lead-in phase, Safety analysis set	Cross-over phase, Safety analysis set	Maintenance phase, Safety analysis set
Measure Participants	11	14	13
Number [adverse events]	0	0	0

18. Secondary Outcome

Title	Abnormal Serum Levels
Description	Safety and tolerability will be described in terms of abnormal serum laboratory values. The reported parameters are not the only ones measured, but rather those for which abnormailities were found
Time Frame	From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ros/Pla <LLN	Ros/Pla >ULN	Pla/Ros <LLN	Pla/Ros >ULN
Arm/Group Description	Safety Analysis Set, starting cross-over phase with 6 weeks of rosuvastatin	Safety Analysis Set, starting cross-over phase with 6 weeks of rosuvastatin	Safety Analysis Set, starting cross-over phase with 6 weeks of placebo	Safety Analysis Set, starting cross-over phase with 6 weeks of placebo
Measure Participants	7	7	7	7
Alanine Aminotransferase week 0	0 0%	0 NaN	0 NaN	0 NaN
Alanine Aminotransferase week 6	0 0%	1 NaN	0 NaN	0 NaN
Alanine Aminotransferase week 12	0 0%	0 NaN	0 NaN	1 NaN
Alanine Aminotransferase week 18	0 0%	0 NaN	0 NaN	1 NaN
Alanine Aminotransferase week 24	0 0%	1 NaN	0 NaN	0 NaN
Albumin week 0	0 0%	0 NaN	0 NaN	1 NaN
Albumin week 6	0 0%	0 NaN	0 NaN	0 NaN
Albumin week 12	0 0%	0 NaN	0 NaN	0 NaN
Albumin week 18	0 0%	0 NaN	0 NaN	1 NaN
Albumin week 24	0 0%	0 NaN	0 NaN	0 NaN
Bicarbonate week 0	1 7.1%	0 NaN	0 NaN	1 NaN
Bicarbonate week 6	0 0%	0 NaN	1 NaN	0 NaN
Bicarbonate week 12	1 7.1%	0 NaN	1 NaN	0 NaN
Bicarbonate week 18	0 0%	0 NaN	1 NaN	0 NaN
Bicarbonate week 24	1 7.1%	0 NaN	1 NaN	0 NaN
Blood Urea Nitrogen week 0	1 7.1%	0 NaN	0 NaN	0 NaN
Blood Urea Nitrogen week 6	1 7.1%	0 NaN	0 NaN	0 NaN
Blood Urea Nitrogen week 12	1 7.1%	0 NaN	0 NaN	0 NaN
Blood Urea Nitrogen week 18	1 7.1%	0 NaN	0 NaN	0 NaN
Blood Urea Nitrogen week 24	0 0%	0 NaN	0 NaN	0 NaN
Chloride week 0	0 0%	2 NaN	0 NaN	1 NaN
Chloride week 6	0 0%	0 NaN	0 NaN	1 NaN
Chloride week 12	0 0%	0 NaN	0 NaN	0 NaN
Chloride week 18	0 0%	1 NaN	0 NaN	1 NaN
Chloride week 24	0 0%	0 NaN	0 NaN	0 NaN
Creatine Kinase week 0	0 0%	0 NaN	0 NaN	0 NaN
Creatine Kinase week 6	0 0%	1 NaN	0 NaN	0 NaN
Creatine Kinase week 12	0 0%	0 NaN	0 NaN	0 NaN
Creatine Kinase week 18	0 0%	0 NaN	0 NaN	0 NaN
Creatine Kinase week 24	0 0%	1 NaN	0 NaN	0 NaN
Glucose week 0	0 0%	1 NaN	0 NaN	0 NaN
Glucose week 6	0 0%	0 NaN	0 NaN	1 NaN
Glucose week 12	0 0%	0 NaN	0 NaN	0 NaN
Glucose week 18	0 0%	1 NaN	0 NaN	1 NaN
Glucose week 24	0 0%	0 NaN	0 NaN	0 NaN
Potassium week 0	0 0%	0 NaN	0 NaN	1 NaN
Potassium week 6	0 0%	0 NaN	0 NaN	0 NaN
Potassium week 12	0 0%	0 NaN	0 NaN	0 NaN
Potassium week 18	0 0%	0 NaN	0 NaN	0 NaN
Potassium week 24	0 0%	0 NaN	0 NaN	0 NaN
Protein week 0	0 0%	0 NaN	0 NaN	0 NaN
Protein week 6	0 0%	0 NaN	0 NaN	0 NaN
Protein week 12	0 0%	0 NaN	0 NaN	1 NaN
Protein week 18	0 0%	0 NaN	0 NaN	0 NaN
Protein week 24	0 0%	0 NaN	0 NaN	1 NaN
Sodium week 0	2 14.3%	0 NaN	0 NaN	0 NaN
Sodium week 6	1 7.1%	0 NaN	0 NaN	0 NaN
Sodium week 12	0 0%	0 NaN	0 NaN	0 NaN
Sodium week 18	3 21.4%	0 NaN	1 NaN	0 NaN
Sodium week 24	0 0%	0 NaN	2 NaN	0 NaN
Total Bilirubin week 0	0 0%	0 NaN	0 NaN	0 NaN
Total Bilirubin week 6	0 0%	1 NaN	0 NaN	0 NaN
Total Bilirubin week 12	0 0%	0 NaN	0 NaN	0 NaN
Total Bilirubin week 18	0 0%	0 NaN	0 NaN	0 NaN
Total Bilirubin week 24	0 0%	0 NaN	0 NaN	0 NaN
Urate week 0	0 0%	1 NaN	0 NaN	0 NaN
Urate week 6	0 0%	1 NaN	0 NaN	1 NaN
Urate week 12	0 0%	1 NaN	0 NaN	0 NaN
Urate week 18	0 0%	1 NaN	0 NaN	1 NaN
Urate week 24	0 0%	1 NaN	0 NaN	1 NaN
Ery. Mean Corpuscular HGB Concentration week 0	2 14.3%	0 NaN	3 NaN	0 NaN
Ery. Mean Corpuscular HGB Concentration week 6	0 0%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular HGB Concentration week 12	3 21.4%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular HGB Concentration week 18	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular HGB Concentration week 24	2 14.3%	0 NaN	3 NaN	0 NaN
Ery. Mean Corpuscular Hemoglobin week 0	1 7.1%	0 NaN	3 NaN	0 NaN
Ery. Mean Corpuscular Hemoglobin week 6	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Hemoglobin week 12	2 14.3%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Hemoglobin week 18	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Hemoglobin week 24	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Volume week 0	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Volume week 6	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Volume week 12	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Volume week 18	1 7.1%	0 NaN	2 NaN	0 NaN
Ery. Mean Corpuscular Volume week 24	1 7.1%	0 NaN	2 NaN	0 NaN
Erythrocytes week 0	1 7.1%	0 NaN	0 NaN	1 NaN
Erythrocytes week 6	0 0%	0 NaN	0 NaN	0 NaN
Erythrocytes week 12	0 0%	0 NaN	1 NaN	1 NaN
Erythrocytes week 18	0 0%	0 NaN	1 NaN	0 NaN
Erythrocytes week 24	0 0%	2 NaN	0 NaN	2 NaN
Hematocrit week 0	2 14.3%	0 NaN	2 NaN	0 NaN
Hematocrit week 6	2 14.3%	0 NaN	3 NaN	0 NaN
Hematocrit week 12	1 7.1%	0 NaN	2 NaN	0 NaN
Hematocrit week 18	1 7.1%	0 NaN	3 NaN	0 NaN
Hematocrit week 24	0 0%	0 NaN	1 NaN	0 NaN
Hemoglobin week 0	2 14.3%	0 NaN	3 NaN	0 NaN
Hemoglobin week 6	2 14.3%	0 NaN	3 NaN	0 NaN
Hemoglobin week 12	1 7.1%	0 NaN	3 NaN	0 NaN
Hemoglobin week 18	1 7.1%	0 NaN	3 NaN	0 NaN
Hemoglobin week 24	0 0%	0 NaN	2 NaN	0 NaN
Lymphocytes/Leukocytes week 0	0 0%	0 NaN	0 NaN	1 NaN
Lymphocytes/Leukocytes week 6	0 0%	0 NaN	0 NaN	1 NaN
Lymphocytes/Leukocytes week 12	0 0%	0 NaN	0 NaN	1 NaN
Lymphocytes/Leukocytes week 18	0 0%	1 NaN	0 NaN	1 NaN
Lymphocytes/Leukocytes week 24	0 0%	1 NaN	0 NaN	1 NaN
Neutrophils, Segmented/Leukocytes week 0	0 0%	0 NaN	0 NaN	0 NaN
Neutrophils, Segmented/Leukocytes week 6	0 0%	0 NaN	0 NaN	0 NaN
Neutrophils, Segmented/Leukocytes week 12	0 0%	0 NaN	0 NaN	0 NaN
Neutrophils, Segmented/Leukocytes week 18	1 7.1%	0 NaN	0 NaN	0 NaN
Neutrophils, Segmented/Leukocytes week 24	1 7.1%	0 NaN	0 NaN	0 NaN
Neutrophils/Leukocytes week 0	0 0%	0 NaN	0 NaN	0 NaN
Neutrophils/Leukocytes week 6	1 7.1%	0 NaN	0 NaN	0 NaN
Neutrophils/Leukocytes week 12	0 0%	0 NaN	0 NaN	0 NaN
Neutrophils/Leukocytes week 18	0 0%	0 NaN	0 NaN	0 NaN
Neutrophils/Leukocytes week 24	0 0%	0 NaN	0 NaN	0 NaN
Platelets week 0	0 0%	1 NaN	0 NaN	0 NaN
Platelets week 6	0 0%	0 NaN	0 NaN	1 NaN
Platelets week 12	0 0%	0 NaN	0 NaN	0 NaN
Platelets week 18	0 0%	0 NaN	0 NaN	0 NaN
Platelets week 24	0 0%	0 NaN	0 NaN	1 NaN

19. Secondary Outcome

Title	Height
Description	Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.
Time Frame	Week 0 (start of cross-over), weeks 6, week 12 and week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ros/Pla	Pla/Ros
Arm/Group Description	Safety Analysis Set, starting cross-over with 6 weeks of rosuvastatin	Safety Analysis Set, starting crossover-phase with 6 weeks of placebo
Measure Participants	7	7
Height (cm) week 0	144.0 (17.82)	140.9 (15.70)
Height (cm) week 6	144.9 (17.70)	141.1 (16.11)
Height (cm) week 12	145.7 (18.07)	142.0 (17.17)
Height (cm) week 18	146.9 (17.68)	142.3 (16.99)
Height (cm) week 24	147.1 (17.94)	143.5 (17.58)

20. Secondary Outcome

Title	Height Z-score
Description	Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.
Time Frame	Week 0 (start of cross-over), weeks 6, week 12 and week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ros/Pla	Pla/Ros
Arm/Group Description	Safety Analysis Set, starting cross-over with 6 weeks of rosuvastatin	Safety Analysis Set, starting crossover-phase with 6 weeks of placebo
Measure Participants	7	7
Height z-score week 0	-0.42 (1.697)	-0.75 (1.555)
Height z-score week 6	-0.29 (1.703)	-0.71 (1.644)
Height z-score week 12	-0.18 (1.742)	-0.70 (1.776)
Height z-score week 18	0.00 (1.721)	-0.65 (1.757)
Height z-score week 24	0.04 (1.752)	-0.49 (1.758)

21. Secondary Outcome

Title	Weight
Description	Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.
Time Frame	Week 0 (start of cross-over), weeks 6, week 12 and week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ros/Pla	Pla/Ros
Arm/Group Description	Safety Analysis Set, starting cross-over with 6 weeks of rosuvastatin	Safety Analysis Set, starting crossover-phase with 6 weeks of placebo
Measure Participants	7	7
Weight (kg) week 0	37.39 (12.731)	40.19 (16.520)
Weight (kg) week 6	38.14 (13.577)	40.36 (16.462)
Weight (kg) week 12	38.63 (14.426)	42.30 (18.651)
Weight (kg) week 18	39.31 (14.588)	42.50 (17.990)
Weight (kg) week 24	39.90 (14.550)	43.00 (17.867)

22. Secondary Outcome

Title	Tanner Stage
Description	Stages for fem (Pubic hair, Breasts): (Preadol,Preadol) (Sparse, lightly pigmented, medial border of labia,Breast and papilla elevated as small mound; areolar diam incr) (Darker, beginning to curl, incr amount, Breast and areola enlarged, no contour separation) (Course, curly, abundant but less amount in adult,Areola and papilla form secondary mound) (Adult fem triangle, spread to medial surface of thighs,Mature, nipple projects, areola part of general breast contour) For males (Pubic hair, Penis, Testes) 1=(None,Preadol,Preadol) 2=(Scanty, long, light pigm,Slight enl,Enl scrotum, pink texture alt) 3=(Darker, starts to curl, small amount,Longer,Larger) 4=(Resembles adult type, but less in quant; course, curly,Larger; glans and breadth increased in size,Larger, scrotum dark) 5=(Adult distr, spread to medial thighs,Adult size,Adult size). Progr at a normal rate is preferred. Regr is not preferred.
Time Frame	Week 0 (start of cross-over)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ros/Pla	Pla/Ros
Arm/Group Description	Safety Analysis Set, starting cross-over with 6 weeks of rosuvastatin	Safety Analysis Set, starting crossover-phase with 6 weeks of placebo
Measure Participants	7	7
Tanner stage week 0	2.0 (1.41)	1.7 (1.11)
Tanner stage week 24	2.3 (1.38)	2.0 (0.2)

23. Secondary Outcome

Title	TG (mg/dL)
Description	Efficacy in terms of triglycerides (TG)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mg/dL]	79.8 (24.48)	119.5 (52.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-30.4
	Confidence Interval	(2-Sided) 95%; -44.2 to -13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	TG (mmol/L)
Description	Efficacy in terms of triglycerides (TG)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [mmol/L]	0.90 (0.277)	1.35 (0.595)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-30.4
	Confidence Interval	(2-Sided) 95%; -44.2 to -13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	LDL C/HDL C
Description	Efficacy in terms of low density lipoprotein cholesterol (LDL C) / high density lipoprotein cholesterol (HDL C)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [ratio]	12.208 (7.8638)	15.600 (9.1317)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-27.6
	Confidence Interval	(2-Sided) 95%; -41.2 to -11.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	TC/HDL C
Description	Efficacy in terms of total cholesterol (TC) / high density lipoprotein cholesterol (HDL C)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [ratio]	13.704 (8.0414)	17.416 (9.5454)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin, C-FAS Placebo
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-25.6
	Confidence Interval	(2-Sided) 95%; -38.1 to -10.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Non-HDL C/HDL C
Description	Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C) / HDL C
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [ratio]	12.704 (8.0414)	16.416 (9.5454)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-28.2
	Confidence Interval	(2-Sided) 95%; -41.7 to -11.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	ApoB/ApoA
Description	Efficacy in terms of apolipoprotein B (ApoB) / apolipoprotein A (ApoA)
Time Frame	Samples taken at Day 42 (week 6) and Day 84 (week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	13	13
Mean (Standard Deviation) [ratio]	2.408 (1.3259)	2.873 (1.4669)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	C-FAS Rosuvastatin
	Comments	cross-over, null hypothesis is no difference between ros and plc.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	statistical significance set at 0.05
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Relative difference in geometric LSM
	Estimated Value	-20.4
	Confidence Interval	(2-Sided) 95%; -32.8 to -5.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Urinalysis Abnormalitites
Description	Safety and tolerability will be described in terms of abnormal urine laboratory values
Time Frame	Week 0, week 6, week 12 and week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ros/Pla	Pla/Ros
Arm/Group Description	Safety Analysis Set, starting crossover-phase with 6 weeks of rosuvastatin	Safety Analysis Set, starting crossover-phase with 6 weeks of placebo
Measure Participants	7	7
Urine Protein week 0	3 21.4%	2 NaN
Urine Protein week 6	1 7.1%	2 NaN
Urine Protein week 12	3 21.4%	2 NaN
Urine Protein week 18	2 14.3%	1 NaN
Urine Protein week 24	2 14.3%	1 NaN
Urine Ketones week 0	1 7.1%	0 NaN
Urine Ketones week 6	0 0%	0 NaN
Urine Ketones week 12	0 0%	0 NaN
Urine Ketones week 18	0 0%	1 NaN
Urine Ketones week 24	0 0%	0 NaN
Urine Blood week 0	1 7.1%	2 NaN
Urine Blood week 6	2 14.3%	1 NaN
Urine Blood week 12	1 7.1%	2 NaN
Urine Blood week 18	1 7.1%	1 NaN
Urine Blood week 24	1 7.1%	1 NaN

30. Secondary Outcome

Title	ECG Abnormalities
Description	Safety and tolerability will be described in terms of abnormal electro cardio gram (ECG)
Time Frame	Week 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set	C-FAS Rosuvastatin	C-FAS Placebo
Arm/Group Description	Safety Analysis Set	Cross-over Full Analysys Set, 6 weeks of Rosuvastatin	Cross-over Full Analysis Set, 6 weeks of Placebo
Measure Participants	14	7	7
Number [participants]	0 0%	0 NaN	0 NaN

31. Secondary Outcome

Title	Physical Exam Abnormalitites
Description	Safety and tolerability will be described in terms of abnormal physical examinations. Only parameters for which abnormalities were found are reported.
Time Frame	Screening, Week 0, week 6, week 12 and week 18, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ros/Pla	Pla/Ros
Arm/Group Description	Safety Analysis Set, starting crossover-phase with 6 weeks of rosuvastatin	Safety Analysis Set, starting crossover-phase with 6 weeks of placebo
Measure Participants	7	7
General Appearance screening	1 7.1%	2 NaN
General Appearance week 0	1 7.1%	2 NaN
General Appearance week 6	1 7.1%	2 NaN
General Appearance week 12	1 7.1%	2 NaN
General Appearance week 18	1 7.1%	2 NaN
General Appearance week 24	1 7.1%	2 NaN
Head and Neck screening	0 0%	2 NaN
Head and Neck week 0	0 0%	2 NaN
Head and Neck week 6	0 0%	2 NaN
Head and Neck week 12	0 0%	2 NaN
Head and Neck week 18	0 0%	2 NaN
Head and Neck week 24	0 0%	1 NaN
Lymph Nodes screening	0 0%	0 NaN
Lymph Nodes week 0	0 0%	1 NaN
Lymph Nodes week 6	0 0%	0 NaN
Lymph Nodes week 12	0 0%	0 NaN
Lymph Nodes week 18	0 0%	0 NaN
Lymph Nodes week 24	0 0%	0 NaN
Skin screening	5 35.7%	2 NaN
Skin week 0	5 35.7%	2 NaN
Skin week 6	5 35.7%	2 NaN
Skin week 12	5 35.7%	2 NaN
Skin week 18	5 35.7%	2 NaN
Skin week 24	5 35.7%	2 NaN

32. Secondary Outcome

Title	Abnormal Vital Signs
Description	Safety and tolerability will be described in terms of abnormal vital signs
Time Frame	From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Analysis Set
Arm/Group Description	Safety Analysis Set
Measure Participants	14
Number [participants]	0 0%

Adverse Events

Arm/Group Title	Lead-in		Cross-over		Maintenance
Arm/Group Description	Lead-in		Cross-over phase		Maintenance phase
All Cause Mortality
	Lead-in		Cross-over		Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lead-in		Cross-over		Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/14 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Lead-in		Cross-over		Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/11 (36.4%)		4/14 (28.6%)		1/13 (7.7%)
Gastrointestinal disorders
Abdominal pain upper	1/11 (9.1%)	1	0/14 (0%)	0	0/13 (0%)	0
General disorders
Influenza like illness	2/11 (18.2%)	2	2/14 (14.3%)	2	0/13 (0%)	0
Peripheral swelling	1/11 (9.1%)	1	0/14 (0%)	0	0/13 (0%)	0
Chest pain	0/11 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Infections and infestations
Influenza	0/11 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Nasopharyngitis	0/11 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Investigations
Blood bicarbonate decreased	0/11 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Upon completion of the Clinical Trial (CT), the Principal Investigator (PI) may prepare the data derived from the CT for publication or presentation. Material should be submitted to the Sponsor for review prior to review or submission for publication, or public dissemination. Publications from individual sites must not precede the primary manuscript, but if not published within twelve months after completion of the CT, the PI has the right to publish or present the methods and results of the CT.