Familial HypercholesterolaemiaPhase 3NCT01078675

An Study to Evaluate Rosuvastatin in Children and Adolescents With Familial Hypercholesterolaemia

A Phase 3 study testing rosuvastatin calcium in people with Familial Hypercholesterolaemia, run by AstraZeneca at 15 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is being carried out to see if the study medication, rosuvastatin, is effective in treating familial hypercholesterolaemia in children and adolescents, and to determine the long term (over 2 years) safety, tolerability and efficacy of the study medication in these patients. Read more about this study

Who is it for?: Ages 6 to 17 years
Conditions the study is for: Familial Hypercholesterolaemia
What is being tested?: rosuvastatin calcium
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 315 participants
Where: 15 sitesin 5 countries
Study dates: Feb 2010to Feb 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

children and adolescents (aged 6 to less than 18 years) with Familial Hypercholesterolaemia
Patients aged between 6 and less than 10 years of age must not be taking a statin medicine

Who cannot join

History of muscle or sensitivity reactions to any statin medicines
Current active liver disease or dysfunction (except a confirmed diagnosis of Gilbert's disease)

Trial locations and contacts

15 sites in 5 countries.

Country

City, postcode or hospital

15 sites in 5 countries

Netherlands6 sites

Research Site
Amsterdam
Research Site
Groningen
Research Site
Hoorn
Research Site
Leiderdorp
Research Site
Rotterdam
Research Site
Waalwijk

Other trials in Netherlands

Canada5 sites

Research Site
Chicoutimi, Quebec
Research Site
Hamilton, Ontario
Research Site
Québec, Quebec
Research Site
Toronto, Ontario
Research Site
Vancouver, British Columbia

Other trials in Canada

Belgium2 sites

Research Site
Leuven, Belgium
Research Site
Leuven

Other trials in Belgium

United States1 site

Research Site
Cincinnati, Ohio

Other trials in United States

Norway1 site

Research Site
Oslo

Other trials in Norway

About this study

Official title: An Efficacy and 2-Year Safety Study of Open-label Rosuvastatin in Children and Adolescents (Aged From 6 to Less Than 18 Years) With Familial Hypercholesterolaemia

This study will also measure levels of drug in the blood and see how well it is tolerated. This is known as pharmacokinetic (PK) analysis.

At baseline only a small number of patients will participate in a single dose PK phase over 24 hours.

In order to see if this medication works, a control group of healthy siblings will help the researchers to compare certain results.

Conditions: Familial Hypercholesterolaemia
Being tested: rosuvastatin calcium
Keywords: Familial Hypercholesterolaemia, pediatric
Medical subject headings: Hyperlipoproteinemia Type II

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

rosuvastatin calciumDrug
Also called Crestor
5 mg, oral, once daily, 24 months
rosuvastatin calciumDrug
Also called Crestor
10 mg, oral, once daily, 24 months
rosuvastatin calciumDrug
Also called Crestor
20 mg, oral, once daily, 24 months

Study groups in NCT01078675
Study group	Role	What they receive
1	Experimental	Not described Receives: Drug: rosuvastatin calcium

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in LDL-C
Negative values represent a decrease and positive values represent an increase. In total, 198 patients were treated. One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Measured: At Month 3, Month 12 and Month 24
Sexual Maturation by Tanner Staging at Baseline
Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.
Measured: At Baseline
Single Dose PK - Cmax
Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing
Measured: Serial blood samples over 24 hours.
Percent Change From Baseline in Height
One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Measured: At Month 12 and Month 24
Sexual Maturation by Tanner Staging at Month 12
Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.
Measured: At Baseline
Sexual Maturation by Tanner Staging at Month 24
Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.
Measured: At Baseline
Single Dose PK - Tmax
Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing
Measured: Serial blood samples over 24 hours
Single Dose PK - AUC(0-24)
Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing
Measured: Serial blood samples over 24 hours

Secondary outcomes (5)

Percent Change From Baseline in HDL-C, TC, TG, Non-HDL-C, LDL-C/HDL-C, TC/HDL-C, Non HDL C/HDL-C, ApoB, ApoA-1, and ApoB/ApoA-1
One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Measured: At Month 3, Month 12 and Month 24
Change From Baseline in Max and Mean Carotid Intima and Media Wall Thickness (cIMT)
One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Measured: At Month 12 and Month 24
Adverse Events
Number of participants with Various Categories of AE's. One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Measured: 2-year study period
Total Duration of Exposure
Total duration of exposure was calculated as [last dose date of rosuva - first dose date of rosuva + 1 day]. One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Measured: 2-year study period
Overal Treatment Adherence
Overall adherence rate was calculated as the weighted mean of adherence rates of all consecutive visits after baseline, in which the adherence rate between 2 consecutive visits was a percentage of the number of rosuvastatin taken divided by duration of exposure. One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Measured: 2-year study period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2010Feb 2013

First posted2 Mar 2010 (estimated)
Study startFeb 2010
Primary completionFeb 2013
Study completionFeb 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Familial HypercholesterolaemiaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 315 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01078675
Sponsor's protocol ID: D3561C00002
Status last verified: Mar 2015
First submitted: 25 Feb 2010
Last updated: 7 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Braamskamp MJAM, Langslet G, McCrindle BW, Cassiman D, Francis GA, Gagne C, Gaudet D, Morrison KM, Wiegman A, Turner T, Miller E, Kusters DM, Raichlen JS, Martin PD, Stein EA, Kastelein JJP, Hutten BA. Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label). Circulation. 2017 Jul 25;136(4):359-366. doi: 10.1161/CIRCULATIONAHA.116.025158. Epub 2017 Jun 7.
PubMed 28592434
Kusters DM, Wiegman A, Kastelein JJ, Hutten BA. Carotid intima-media thickness in children with familial hypercholesterolemia. Circ Res. 2014 Jan 17;114(2):307-10. doi: 10.1161/CIRCRESAHA.114.301430. Epub 2013 Nov 5.
PubMed 24192652
Tolani S, Pagler TA, Murphy AJ, Bochem AE, Abramowicz S, Welch C, Nagareddy PR, Holleran S, Hovingh GK, Kuivenhoven JA, Tall AR. Hypercholesterolemia and reduced HDL-C promote hematopoietic stem cell proliferation and monocytosis: studies in mice and FH children. Atherosclerosis. 2013 Jul;229(1):79-85. doi: 10.1016/j.atherosclerosis.2013.03.031. Epub 2013 Apr 19.
PubMed 23684512

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Not yet recruitingObservational study
An Observational Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia
Hypercholesterolaemia, Familial Hypercholesterolaemia
Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
Active, not recruitingObservational study
Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia

All Familial Hypercholesterolaemia trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Efficacy and 2-Year Safety Study of Open-label Rosuvastatin in Children and Adolescents (Aged From 6 to Less Than 18 Years) With Familial Hypercholesterolaemia
ClinicalTrials.gov ID: NCT01078675
Acronym / sponsor ID: D3561C00002
Conditions: Familial Hypercholesterolaemia
Keywords: Familial Hypercholesterolaemia, pediatric
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 315 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Feb 2010
Primary completion: Feb 2013 (actual)
Study completion: Feb 2013 (actual)
First posted: 2 Mar 2010 (estimated)
Results: Posted 2 Feb 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will also measure levels of drug in the blood and see how well it is tolerated. This is known as pharmacokinetic (PK) analysis.

At baseline only a small number of patients will participate in a single dose PK phase over 24 hours.

In order to see if this medication works, a control group of healthy siblings will help the researchers to compare certain results.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
1	Experimental	Drug: rosuvastatin calcium

Who may qualify

Ages: 6 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

children and adolescents (aged 6 to less than 18 years) with Familial Hypercholesterolaemia
Patients aged between 6 and less than 10 years of age must not be taking a statin medicine

Key exclusion criteria (2 listed)

History of muscle or sensitivity reactions to any statin medicines
Current active liver disease or dysfunction (except a confirmed diagnosis of Gilbert's disease)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
rosuvastatin calciumAlso: Crestor5 mg, oral, once daily, 24 months	Drug	1
rosuvastatin calciumAlso: Crestor10 mg, oral, once daily, 24 months	Drug	1
rosuvastatin calciumAlso: Crestor20 mg, oral, once daily, 24 months	Drug	1

Primary outcome

Percent Change From Baseline in LDL-C
Time frame: At Month 3, Month 12 and Month 24
Negative values represent a decrease and positive values represent an increase. In total, 198 patients were treated. One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Sexual Maturation by Tanner Staging at Baseline
Time frame: At Baseline
Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.
Single Dose PK - Cmax
Time frame: Serial blood samples over 24 hours.
Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing
Percent Change From Baseline in Height
Time frame: At Month 12 and Month 24
One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.
Sexual Maturation by Tanner Staging at Month 12
Time frame: At Baseline
Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.
Sexual Maturation by Tanner Staging at Month 24
Time frame: At Baseline
Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.
Single Dose PK - Tmax
Time frame: Serial blood samples over 24 hours
Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing
Single Dose PK - AUC(0-24)
Time frame: Serial blood samples over 24 hours
Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing

5 secondary outcomes

Percent Change From Baseline in HDL-C, TC, TG, Non-HDL-C, LDL-C/HDL-C, TC/HDL-C, Non HDL C/HDL-C, ApoB, ApoA-1, and ApoB/ApoA-1
Time frame: At Month 3, Month 12 and Month 24
Change From Baseline in Max and Mean Carotid Intima and Media Wall Thickness (cIMT)
Time frame: At Month 12 and Month 24
Adverse Events
Time frame: 2-year study period
Total Duration of Exposure
Time frame: 2-year study period
Overal Treatment Adherence
Time frame: 2-year study period

Results and safety

Results posted to the registry on 2 Feb 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rosuvastatin	250	182
Healthy Siblings	65	59

Primary outcome: Percent Change From Baseline in LDL-C

Time frame: At Month 3, Month 12 and Month 24. Mean (Standard Deviation). Unit: Percentage change

Measure	Rosuvastatin n = 197
LDL-C %Change from Baseline at month 3	-37.86 (14.392)
LDL-C %Change from Baseline at month 12	-43.67 (14.896)
LDL-C %Change from Baseline at month 24	-42.88 (18.222)

Rosuvastatin: Mean Difference (Final Values): -42.88 (-42.88% CI -45.44 to -40.32), p <0.001, ANCOVA

Population analysed: Intent-to-treat analysis set and Per-protocol analysis set

Primary outcome: Sexual Maturation by Tanner Staging at Baseline

Time frame: At Baseline. Number. Unit: Participants

Measure	Rosuvastatin n = 197
Tanner Stage I at Baseline	81 (NA)
Tanner Stage II at Baseline	32 (NA)
Tanner Stage III at Baseline	18 (NA)
Tanner Stage IV at Baseline	44 (NA)
Tanner Stage V at Baseline	21 (NA)
Not Recorded at Baseline	1

Population analysed: Safety analysis set

Primary outcome: Single Dose PK - Cmax

Time frame: Serial blood samples over 24 hours.. Mean (Standard Deviation). Unit: ng/mL

Measure	Rosuvastatin n = 12
Value	3.5717 (3.22350)

Population analysed: Single dose PK analysis set

Primary outcome: Percent Change From Baseline in Height

Time frame: At Month 12 and Month 24. Mean (Standard Deviation). Unit: Percent change

Measure	Rosuvastatin n = 197
%Change from Baseline at Month 12	3.20 (2.023)
%Change from Baseline at Month 24	5.91 (3.968)

Population analysed: Safety Population

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment Phase. Other adverse events reported at 0.5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rosuvastatin	9 of 197 (4.6%)	172 of 197 (87.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28592434Braamskamp MJAM, Langslet G, McCrindle BW, Cassiman D, Francis GA, Gagne C, Gaudet D, Morrison KM, Wiegman A, Turner T, Miller E, Kusters DM, Raichlen JS, Martin PD, Stein EA, Kastelein JJP, Hutten BA. Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label). Circulation. 2017 Jul 25;136(4):359-366. doi: 10.1161/CIRCULATIONAHA.116.025158. Epub 2017 Jun 7.
Derived from this study: PubMed 24192652Kusters DM, Wiegman A, Kastelein JJ, Hutten BA. Carotid intima-media thickness in children with familial hypercholesterolemia. Circ Res. 2014 Jan 17;114(2):307-10. doi: 10.1161/CIRCRESAHA.114.301430. Epub 2013 Nov 5.
Derived from this study: PubMed 23684512Tolani S, Pagler TA, Murphy AJ, Bochem AE, Abramowicz S, Welch C, Nagareddy PR, Holleran S, Hovingh GK, Kuivenhoven JA, Tall AR. Hypercholesterolemia and reduced HDL-C promote hematopoietic stem cell proliferation and monocytosis: studies in mice and FH children. Atherosclerosis. 2013 Jul;229(1):79-85. doi: 10.1016/j.atherosclerosis.2013.03.031. Epub 2013 Apr 19.
D3561C00002 Study Report SynopsisLink provided by the sponsor.

Related trials for Familial Hypercholesterolaemia

Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Not yet recruitingObservational study
An Observational Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia
Hypercholesterolaemia, Familial Hypercholesterolaemia
Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
Active, not recruitingObservational study
Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John J.P. Kastelein, MD, PhD principal investigator

Chairman, Dept. of Vascular Medicine, Academic Medical Center, Meibergdreef 9

15 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rosuvastatin calcium in people with Familial Hypercholesterolaemia, run by AstraZeneca at 15 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Netherlands, Canada, Belgium, United States, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in LDL-C (time frame: At Month 3, Month 12 and Month 24). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01078675, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2015.