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Bosentan in Children With Pulmonary Arterial Hypertension (FUTURE-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00319267
First received: April 26, 2006
Last updated: May 23, 2016
Last verified: May 2016
  Purpose
The aim of the study is to demonstrate that the exposure to bosentan in children with idiopathic pulmonary arterial hypertension (PAH) or familial pulmonary arterial hypertension, using a pediatric formulation, is similar to that in adults with PAH and to evaluate the tolerability and safety of a pediatric formulation of bosentan in this patient population.

Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Bosentan
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Multicenter Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Pediatric Formulation of Bosentan in Children With Idiopathic or Familial Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Area under the plasma concentration-time curve during a dose interval (AUCt) for bosentan [ Time Frame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose ] [ Designated as safety issue: No ]
    AUCt was assessed at steady state (i.e., after at least 2 weeks of treatment with a same dose of the study drug) over 12 hours .


Secondary Outcome Measures:
  • Maximum plasma concentration (Cmax) of bosentan and its metabolites [ Time Frame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration for bosentan and its metabolites was directly derived from their respective plasma concentration-time curves.

  • Time to reach the maximum plasma concentration (tmax) of bosentan and its metabolites [ Time Frame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve during a dose interval (AUCt) for the metabolites of bosentan [ Time Frame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose ] [ Designated as safety issue: No ]
    AUCt was assessed at steady state (i.e., after at least 2 weeks of treatment with a same dose of the study drug) over 12 hours.


Enrollment: 36
Study Start Date: May 2005
Study Completion Date: February 2007
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bosentan
The initial dose of bosentan was 2 mg/kg b.i.d. for 4 weeks. After 4 weeks, the initial dose was up-titrated to the maintenance dose of 4 mg/kg b.i.d. up to the end of the study treatment at Week 12. If the maintenance dose was not well tolerated, the dose could be down-titrated to the initial dose.
Drug: Bosentan
Pediatric oral formulation of bosentan, i.e., 32 mg dispersible and breakable tablets
Other Names:
  • ACT-050088
  • Ro 47-0203

  Eligibility

Ages Eligible for Study:   2 Years to 12 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent by the parents or the legal representatives.
  • Males or females >= 2 and < 12 years of age.
  • Idiopathic PAH or familial PAH diagnosed by right heart catheterization (Clinical classification of pulmonary hypertension, Venice 2003).
  • World Health Organization (WHO) functional class II or III.
  • Oxygen saturation (SpO2) >= 88% (at rest, on room air).
  • PAH treatment-naïve patients or patients already treated with either:

    • Bosentan monotherapy
    • Intravenous epoprostenol monotherapy
    • Intravenous or inhaled iloprost monotherapy
    • Combination of bosentan and intravenous epoprostenol
    • Combination of bosentan and intravenous or inhaled iloprost.
  • All patients should start the study drug (bosentan pediatric formulation) at 2 mg/kg twice daily (b.i.d.), whether or not they were previously treated with bosentan.
  • PAH therapy stable for at least 3 months prior to Screening.
  • Stable treatment with calcium channel blockers, if any, for at least 3 months prior to Screening.
  • Patient's PAH condition stable for at least 3 months prior to Screening.

Exclusion Criteria:

  • PAH associated with conditions other than idiopathic or familial PAH.
  • Non-stable patients, e.g., history (in the last 3 months prior to Screening) of recurrent syncope, or signs and symptoms of non-compensated right heart failure.
  • Need or plan to wean patients from intravenous epoprostenol, or intravenous, or inhaled iloprost.
  • Body weight < 4 kg.
  • Systolic blood pressure < 80%, the lower limit of normal range, according to age and gender.
  • AST and/or ALT values > 3 times the upper limit of normal ranges.
  • Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
  • Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal ranges.
  • Pregnancy.
  • Known intolerance or hypersensitivity to bosentan or any of the excipients.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319267

Locations
United States, Colorado
The Children's Hospital Cardiac Care Center
Denver, Colorado, United States, 80218
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
France
Hopital Antoine Beclere
Clamart, France, 92140
Hopital Necker
Paris, France, 75743
CHE de Toulouse Hopital d'Enfants
Toulouse, France
Germany
Deutsches Herzzentrum
Augustenburger, Germany
Universitats Kinderklinik
Giessen, Germany
Italy
Policlinico S. Orsola-Malpighi
Bologna, Italy, 40138
Netherlands
Beatrix Children's Hospital
Groningen, Netherlands
Switzerland
Hopital des Enfants
Geneva, Switzerland
United Kingdom
The Institute of Child Health
London, United Kingdom
Sponsors and Collaborators
Actelion
  More Information

Publications:
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00319267     History of Changes
Other Study ID Numbers: AC-052-365  2004-005157-63 
Study First Received: April 26, 2006
Last Updated: May 23, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
bosentan
children
pharmacokinetics
pulmonary arterial hypertension

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Bosentan
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 28, 2016