A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Rivaroxaban for Thromboprophylaxis in Pediatric Subjects 2 to 8 Years of Age after the Fontan Procedure

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-002610-76-ES
• Date of registration: 05/08/2016
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V
• Public title: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Rivaroxaban for Thromboprophylaxis in Pediatric Subjects 2 to 8 Years of Age after the Fontan Procedure
• Scientific title: A Prospective, Open-Label, Active-Controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Rivaroxaban for Thromboprophylaxis in Pediatric Subjects 2 to 8 Years of Age after the Fontan Procedure
• Date of first enrolment: 19/09/2016
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002610-76
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, China, France, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Spain, Thailand, United Kingdom, United States

Contacts

• Name: Global Clinical Operations Spain
• Affiliation: Janssen Cilag, S.A.

• Name: Global Clinical Operations Spain
• Affiliation: Janssen Cilag, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Boys or girls 2 to 8 years of age with single ventricle physiology and who have completed the initial Fontan procedure within 4 months prior to enrollment
2. Considered to be clinically stable by the investigator and able to tolerate oral or enteral administration of a suspension formulation and oral/enteral feedings
3. Satisfactory initial post-Fontan transthoracic echocardiographic screening as defined in the Post-Fontan Echocardiographic Examination Research Protocol
4. Parent/legally acceptable representative must sign an informed consent form (ICF) and child assent will also be provided, if applicable, according to local requirements.
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Evidence of thrombosis, including those that are asymptomatic confirmed by post-Fontan procedure transthoracic echocardiogram, or other imaging techniques, during the screening period of the study
2. History of gastrointestinal disease or surgery associated with clinically relevant impaired absorption
3. History of or signs/symptoms suggestive of protein-losing enteropathy
4. Active bleeding or high risk for bleeding contraindicating antiplatelet or anticoagulant therapy, including a history of intracranial bleeding
5. Indication for anticoagulant or antiplatelet therapy other than current study, however:
- A subject who has received VKA after the Fontan procedure may be eligible provided that the subject has discontinued VKA before the screening visit. Baseline laboratory samples must be obtained at least 7 days after the last dose of VKA.
- A subject who is receiving ASA at the time of the screening visit may be eligible and may continue on ASA provided the last dose is taken at least 24 hours prior to the first dose of study drug.
6. Platelet count <50 x 10^9/L at screening.
7. Creatinine clearance (CrCl) <30 mL/min/1.73m2.
8. Known clinically significant liver disease.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Thromboprophylaxis
MedDRA version: 19.0 Level: LLT Classification code 10040729 Term: Single ventricle System Organ Class: 100000004850

Intervention(s)

Product Name: Xarelto
Product Code: JNJ-39039039; BAY 59-7939
Pharmaceutical Form: Granules for oral solution
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: JNJ-39039039; BAY 59-7939
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Aspirin
Product Name: acetylsalicylic acid
Pharmaceutical Form: Tablet
INN or Proposed INN: ACETYLSALICYLIC ACID
CAS Number: 50-78-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): Part A:
PK and PD Parameters: PT, aPTT and anti-FXa activity against Rivaroxaban plasma concentration.
PK: AUC (O-24), Cmax after single dose and AUC (0-24), Cmax and Cmin at steady state

Part B:
Efficacy: Thrombotic events (venous or arterial), defined as:
- The appearance of a new thrombotic burden within the cardiovascular system on either routine surveillance or clinically indicated imaging, or
- The occurrence of a clinical event known to be strongly associated with thrombus (such as cardioembolic stroke, pulmonary embolism).
Safety: major bleeding events as defined by ISTH

Main Objective: Part A
To characterize the single- and multiple-dose PK and PK/ PD profiles after oral rivaroxaban therapy administered to pediatric subjects 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment.

Part B
To evaluate the safety and efficacy of rivaroxaban, administered twice daily (exposure matched to rivaroxaban 10 mg once daily in adults) compared to ASA, given once daily (approximately 5 mg/kg) for thromboprophylaxis in pediatric subjects 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment.

Secondary Objective: Part A
To assess the safety and tolerability of rivaroxaban treatment.
Part B
To further characterize the PK and PK/PD profiles of rivaroxaban.

Timepoint(s) of evaluation of this end point: Part A:
Day 1, 4, Month 3, Month 12

Part B:
Ongoing throughout the study as well as at pre-defined time points (Day 12, Months 3, 6 and 12) from enrollment until final follow-up phone call

Secondary Outcome(s)

Secondary end point(s): Part A:
Efficacy: Thrombotic events (venous or arterial), defined as:
- The appearance of a new thrombotic burden within the cardiovascular system on either routine surveillance or clinically indicated imaging, or
- The occurrence of a clinical event known to be strongly associated with thrombus (such as cardioembolic stroke, pulmonary embolism).
Any death
Safety: major bleeding events, Clinically relevant non-major bleeding events and trivial (minimal) bleeding as defined by ISTH; other adverse events and clinical laboratory test values (CBC, CrCl, liver function tests, and PT and aPTT).


Part B:
PK/PD Parameters: PT, aPTT and anti-FXa activity against Rivaroxaban plasma concentration.
PK: AUC (O-24), Cmax after single dose and AUC (0-24), Cmax and Cmin at steady state
Safety: Clinically relevant non-major bleeding events and trivial (minimal) bleeding as defined by ISTH; any death, other adverse events and clinical laboratory test values(CBC, CrCl, liver function tests, and PT and aPTT) .

Timepoint(s) of evaluation of this end point: Part A:
Ongoing throughout the study as well as at pre-defined time points (Day 12, Months 3, 6 and 12) from enrollment until final follow-up examination

Part B:
Day 1, Month 3, Month 12

Secondary ID(s)

2015-002610-76-BE

39039039CHD3001/BAY59-7939-18226

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date:
Contact: