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

NCT02434497 | Completed Phase 3 Results

• 1 other identifier: D356NC00001
• Study Type: interventional
• Target: 9
• Locations: 6 countries
• Sites: 6

Brief Summary

The purpose of the study is to evaluate the safety of Rosuvastatin in Children and Adolescents with Homozygous Familial Hypercholesterolemia.

Conditions

Homozygous Familial Hypercholesterolemia (HoFH)

Keywords

LDL-C; HoFH; Hyperlipidemia

Outcome Measures

Primary Outcomes (44)

• The Number of Participants Who Experianced Adverse Events and Serious Adverse Events

  96 weeks

• Safety and Tolerability in Terms of Number of Participants Who Had Adverse Events, Discontinuations Due to Adverse Events

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN)

  96 weeks

• Safety and Tolerability in Terms of Growth, Height

  96 weeks

• Safety and Tolerability in Terms of Abnormalitites in Sexual Maturation

  96 weeks

• Safety and Tolerability in Terms of Growth, Height SD-score (or Z-score)

  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

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Alanine Aminotransferase (U/L) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Albumin (g/dL) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Aspartate Aminotransferase (U/L) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB (pg) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hematocrit (%) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hemoglobin (g/dL) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Leukocytes >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Monocytes/Leukocytes (%) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Platelets (10^9/L) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Blood Urea Nitrogen (mg/dL) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Chloride (mmol/L) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Creatine Kinase (U/L) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Glucose (mg/dL) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lactate Dehydrogenase (U/L) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Phosphate (mg/dL) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Protein (g/dL) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Sodium (mmol/L) <LLN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Urate (mg/dL) >ULN

  96 weeks

• Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Ketones

  96 weeks

• Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Occult Blood

  96 weeks

• Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Protein

  96 weeks

• Safety and Tolerability in Terms of Abnormal ECG, Abnormalities

  96 weeks

• Safety and Tolerability in Terms of Abnormal Physical Exams, Cardiovascular

  96 weeks

• Safety and Tolerability in Terms of Abnormal Physical Exams, General Appearance

  96 weeks

• Safety and Tolerability in Terms of Abnormal Physical Exams, Head and Neck

  96 weeks

• Safety and Tolerability in Terms of Abnormal Physical Exams, Musculoskeletal/Extremities

  96 weeks

• Safety and Tolerability in Terms of Abnormal Physical Exams, Skin

  96 weeks

• Safety and Tolerability in Terms of Abnormal Vital Signs

  96 weeks

Secondary Outcomes (12)

• Percent Change in LDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis

  Up to 22 months

• Percent Change in HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis

  Up to 22 months

• Percent Change in Total Cholesterol (TC) From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis

  Up to 22 months

• Percent Change in Triglycerides (TG) From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis

  Up to 22 months

• Percent Change in Non-HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis

  Up to 22 months

Study Arms (1)

Single Arm

EXPERIMENTAL

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.

Drug: Rosuvastatin 20mg

Interventions

Rosuvastatin 20mg DRUG

Active drug 1 or 2 tablets will be taken taken orally, QD, either in the morning or in the evening

Single Arm

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (6)

Research Site

Brussels (Woluwé-St-Lambert), 1200, Belgium

Location

Research Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Research Site

Copenhagen, DK-2100, Denmark

Location

Research Site

Halfa, 31096, Israel

Location

Research Site

Kubang Kerian, 16150, Malaysia

Location

Research Site

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia; Hyperlipidemias

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Robin Mukherjee
• Organization: AstraZeneca Plc

robin.mukherjee@astrazeneca.com

+46317761000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2015
• First Posted: May 5, 2015
• Study Start: June 6, 2015
• Primary Completion: November 17, 2016
• Study Completion: November 17, 2016
• Last Updated: February 27, 2018
• Results First Posted: February 27, 2018

Record last verified: 2018-02

Locations

MY (1); IL (1); BE (1); CA (1); DK (1); TW (1)