Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
Condition: Hypertension, Pulmonary
MeSH terms: Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension
Intervention: Ambrisentan
Intervention description: open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day
Intervention MeSH terms: Ambrisentan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 8 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: pulmonary arterial hypertension; pediatrics

Summary:

      An open label, long term extension to Study AMB112529. All subjects may remain in the
      extension study for a minimum of six months. Beyond the six month period, subjects may
      continue in the extension study until one of the following conditions is met:

      the subject turns 18 years of age (when the subject can receive marketed product) the product
      is approved and available for use in the subject's age group, development for use in the
      paediatric population is discontinued. the subject decides he/she no longer wants to
      participate in the study, the investigator considers it is in the best interest of the
      subject to discontinue ambrisentan (e.g. for safety reasons).

      The primary objective is the long-term safety and tolerability of ambrisentan in the
      paediatric PAH population. Secondary objectives are all cause mortality and change from
      baseline in Study AMB112529 on efficacy parameters.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have participated in and complied, to the best of their ability, with the protocol for
             AMB112529 and have met one of the following:

               1. Completed the Week 24 visit in AMB112529;

               2. Required additional targeted treatment for PAH due to inadequate response to the
                  current treatment or worsening of their clinical condition prior to week 24 in
                  AMB112529;

               3. Required reduction in dose of baseline targeted treatment for PAH after
                  ambrisentan was added to the treatment regimen;

               4. In the opinion of the investigator, continued treatment with ambrisentan is
                  warranted.

          -  A female is eligible to participate in this study, as assessed by the investigator, if
             she is of:

               1. Non-childbearing potential (i.e., physiologically incapable of becoming
                  pregnant); or,

               2. Child-bearing potential - has a negative pregnancy test and is not lactating and,
                  if sexually active, agrees to continue to use 2 reliable methods of contraception
                  until study completion and for at least 30 days following the last dose of study
                  drug (reliable methods of contraception are listed in Appendix 2).

          -  Subject or subject's legal guardian is able and willing to give written informed
             consent. As part of the consent, female subjects of childbearing potential will be
             informed of the risk of teratogenicity and will need to be counselled in a
             developmentally appropriate manner on the importance of pregnancy prevention; and male
             subjects will need to be informed of potential risk of testicular tubular atrophy and
             aspermia.

        Exclusion Criteria:

          -  Subjects who were withdrawn from ambrisentan in Study AMB112529;

          -  Subjects who did not comply with the protocol in Study AMB112529;

          -  Female subjects who are pregnant or breastfeeding;

          -  Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min
             assessed within the previous 45 days) at the point of transition from Study AMB112529
             into this study;

          -  Subject with clinically significant fluid retention in the opinion of the
             investigator;

          -  Subject with clinically significant anaemia in the opinion of the investigator;

          -  Subjects who are to enter another clinical trial or be treated with another
             investigational product after exiting Study AMB112529.