- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02434497
A Study to Evaluate the Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
An Open-Label Long-Term Extension to the 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 Overview
Status
Intervention / Treatment
Detailed Description
This is a long-term extension (LTE) to the randomized, double-blind, cross-over study of rosuvastatin 20 mg once daily (QD) versus placebo QD in children and adolescents (aged from 6 to <18 years) with homozygous familial hypercholesterolemia (HoFH) (Study D3561C00004).
The study is designed to assess the long-term safety and tolerability of rosuvastatin 20 mg in pediatric patients with HoFH.
In this study all patients will receive rosuvastatin 20 mg QD. Investigators will also be permitted to titrate the dose of rosuvastatin from 20 to 40 mg per day if they feel it is warranted to more aggressively treat patients' elevated LDL-C levels. This up-titration will not be permitted in Asian patients. Pharmacokinetic data of the trough plasma exposure of rosuvastatin will also be assessed for the pediatric patients with HoFH taking a daily dose of rosuvastatin 40 mg.
The primary outcome measures to be assessed include 1) Adverse events, including:
- The frequency and severity of adverse events,
- Rate of discontinuations due to adverse events,
- Abnormal serum and urine laboratory values, electrocardiograms (ECGs), physical examinations, and vital signs; and 2) Assessments of growth.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Brussels (Woluwé-St-Lambert), Belgium, 1200
- Research Site
-
-
-
-
Quebec
-
Chicoutimi, Quebec, Canada, G7H 7K9
- Research Site
-
-
-
-
-
Copenhagen, Denmark, DK-2100
- Research Site
-
-
-
-
-
Halfa, Israel, 31096
- Research Site
-
-
-
-
-
Kubang Kerian, Malaysia, 16150
- Research Site
-
-
-
-
-
Taipei City, Taiwan, 11217
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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 [IEC] according to local regulations and guidelines). Study D3561C00004 participants who have had their 18th birthday (adults) will be required to provide written informed consent. Communication should take place between the Investigator, patient/guardian and child/adolescent to confirm understanding and required compliance with the requirements of the study.
Male and female children and adolescents who were aged 6 to <18 years at the onset of Study D3561C00004 (even if they had their 18th birthday during that study) with:
- 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 TG <400 mg/dL (4.5 mmol/L) and at least 1 of the following criteria:
- Tendinous and/or cutaneous xanthoma prior to 10 years of age; or
- Documentation of HeFH in both parents by:
- genetic and/or
- clinical criteria
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
- Were taking study drug at the end of Study D3561C00004 and are willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.
Exclusion Criteria:
- History of statin inducted myopathy or serious hypersensitivity reaction to other HMG CoA reductase inhibitors (statins), including rosuvastatin, at Visit 1 of Study D3561C00004.
- Fasting serum glucose of >9.99 mmol/L (180 mg/dL) or glycosylated hemoglobin >9% during Study D3561C00004 or patients with a history of diabetic ketoacidosis within the past year.
- Uncontrolled hypothyroidism defined as thyroid stimulating hormone >1.5 times the upper limit of normal (ULN) at any time during Study D3561C00004.
- Evidence of active liver disease or hepatic dysfunction (except a confirmed diagnosis of Gilbert's disease) as defined as non-transient elevations of ALT or AST elevations ≥3 times the ULN or non-transient total bilirubin ≥2 times the ULN during the Study D3561C00004.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single Arm
One treatment period for all patients (<1 year and 10 months), with the possibility to up-titrate dose to 40 mg of rosuvastatin for non-Asian patients.
|
Active drug 1 or 2 tablets will be taken taken orally, QD, either in the morning or in the evening
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Number of Participants Who Experianced Adverse Events and Serious Adverse Events
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Number of Participants Who Had Adverse Events, Discontinuations Due to Adverse Events
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN)
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Growth, Height
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormalitites in Sexual Maturation
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Growth, Height SD-score (or Z-score)
Time Frame: 96 weeks
|
Height z-score is a dimensionless quantity derived by subtracting the population mean from the individual raw score, and then deviding the difference by the pouulation SD of the reference population.
This indicates how many SDs and observation is above or below the general population mean.
|
96 weeks
|
Safety and Tolerability in Terms of Growth, Weight
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Alanine Aminotransferase (U/L) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Albumin (g/dL) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Aspartate Aminotransferase (U/L) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB (pg) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hematocrit (%) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hemoglobin (g/dL) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Leukocytes >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Monocytes/Leukocytes (%) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Platelets (10^9/L) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Blood Urea Nitrogen (mg/dL) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Chloride (mmol/L) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Creatine Kinase (U/L) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Glucose (mg/dL) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lactate Dehydrogenase (U/L) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Phosphate (mg/dL) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Protein (g/dL) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Sodium (mmol/L) <LLN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Urate (mg/dL) >ULN
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Ketones
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Occult Blood
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Protein
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal ECG, Abnormalities
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Physical Exams, Cardiovascular
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Physical Exams, General Appearance
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Physical Exams, Head and Neck
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Physical Exams, Musculoskeletal/Extremities
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Physical Exams, Skin
Time Frame: 96 weeks
|
96 weeks
|
|
Safety and Tolerability in Terms of Abnormal Vital Signs
Time Frame: 96 weeks
|
96 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percent Change in LDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in Total Cholesterol (TC) From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in Triglycerides (TG) From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in Non-HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in LDL-C/HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in TC/HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in Non-HDL-C/HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in ApoB From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in ApoA-1 From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Percent Change in ApoB/ApoA-1 From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis
Time Frame: Up to 22 months
|
Up to 22 months
|
Pharmacokinetic Profile in Terms of Trough Concentrations in Pediatric HoFH Taking a Daily Dose of Rosuvastatin 40mg
Time Frame: Up to 22 months
|
Up to 22 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lipid Metabolism Disorders
- Hyperlipidemias
- Dyslipidemias
- Lipid Metabolism, Inborn Errors
- Hyperlipoproteinemias
- Hypercholesterolemia
- Hyperlipoproteinemia Type II
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Rosuvastatin Calcium
Other Study ID Numbers
- D356NC00001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Homozygous Familial Hypercholesterolemia (HoFH)
-
REGENXBIO Inc.National Heart, Lung, and Blood Institute (NHLBI)TerminatedHomozygous Familial Hypercholesterolemia (HoFH)United States, Canada, Italy, Netherlands
-
AstraZenecaCompletedHomozygous Familial Hypercholesterolemia (HoFH)Malaysia, Canada, Israel, Netherlands, Taiwan, Belgium, Denmark
-
HDL TherapeuticsMedStar Heart and Vascular InstituteUnknownHomozygous Familial Hypercholesterolemia | HoFHUnited States
-
AmgenCompletedHomozygous Familial Hypercholesterolemia HoFHIndia
-
Amryt PharmaActive, not recruitingHomozygous Familial Hypercholesterolaemia (HoFH)Germany, Israel, Italy, Saudi Arabia, Spain, Tunisia
-
Organon and CoCompletedPrimary Hypercholesterolemia and Homozygous Familial Hypercholesterolemia (HoFH)
-
REGENXBIO Inc.Active, not recruitingHomozygous Familial Hypercholesterolemia (HoFH)United States, Canada, Netherlands
-
REGENXBIO Inc.CompletedHomozygous Familial Hypercholesterolemia (HoFH)United States
-
Novartis PharmaceuticalsActive, not recruitingFamilial Hypercholesterolemia - HomozygousGreece, Lebanon, Turkey, France, Canada, Malaysia, Netherlands, United States
-
Novartis PharmaceuticalsRecruitingHeterozygous or Homozygous Familial HypercholesterolemiaNetherlands, Israel, Hungary, Italy, Germany, Spain, France, Norway, South Africa, Turkey, United Kingdom, Canada, Switzerland, Brazil, Lebanon, Slovenia, United States, Russian Federation, Taiwan
Clinical Trials on Rosuvastatin 20mg
-
Hanmi Pharmaceutical Company LimitedCompletedHealthyKorea, Republic of
-
EMSWithdrawn
-
Samsung Medical CenterDon-A Pharmaceutical, Seoul, South KoreaUnknownStroke | Intracranial AtherosclerosisKorea, Republic of
-
Kiyuk Chang, MD,PhDRecruitingMyocardial Infarction | Statin Adverse Reaction | HMG-CoA Reductase Inhibitor ToxicityKorea, Republic of
-
IlDong Pharmaceutical Co LtdUnknownHypertension | HyperlipidemiaKorea, Republic of
-
Yuhan CorporationLinical KoreaTerminatedA Clinical Trial of YMC017 in Hypertensive and Hypercholesterolemic Patients With Metabolic SyndromeMetabolic SyndromeKorea, Republic of
-
Alvogen KoreaCompletedPrimary HypercholesterolemiaKorea, Republic of
-
Keun-Sik HongSamsung Medical Center; Seoul St. Mary's Hospital; Seoul National University... and other collaboratorsUnknownStroke, IschemicKorea, Republic of
-
Laboratorios Silanes S.A. de C.V.Completed
-
Hanmi Pharmaceutical Company LimitedCompletedDiabetes MellitusKorea, Republic of