The main purpose of this study is to evaluate the safety and efficacy of tadalafil in pediatric participants with pulmonary arterial hypertension. Participants will receive study treatment for 6 months in the double-blind period (Period 1), and then will be eligible to enroll into an open-label 2 year extension period (Period 2) during which participants will receive tadalafil.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
35
Administered orally by tablet form for heavy and middle weight participants. Administered orally by suspension for light weight participants.
Administered orally by tablet for heavy and middle weight participants. Administered orally by suspension for light weight participants.
All participants were taking endothelin receptor antagonist (ERA) (such as bosentan, ambrisentan and macitentan).
Period 1: Change From Baseline to Week 24 in a 6 Minute Walk (MW) Distance in Meters
6MWD in meters assessed in a subset of participants who are ≥6 to \<18 years of age who are developmentally capable of performing a 6MW test. Change from baseline was derived using mixed model repeated measures (MMRM) with terms for treatment group, visit, baseline 6MWD, and treatment-by-visit interaction.
Time frame: Baseline, Week 24
Period 1: Time to Adjudicated Clinical Worsening (CW)
Clinical worsening was defined as any of the following: death,lung or heart transplantation,atrial septostomy or Potts' shunt,hospitalization for Pulmonary Arterial Hypertension(PAH) progression,new onset syncope,initiation of new PAH therapy(including increase in the dose of existing PAH specific concomitant therapy,such as endothelin receptor agonist or beraprost medication), or increase of 1 or more in World Health Organization(WHO) Functional Class(except for participants already in Class IV;only for participants unable to perform the 6 minute walk(6MW) test;worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk(6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance(for those participants who are ≥6 years of age). Criteria for CW(from Period 1) were adjudicated by an independent,blinded study-specific Clinical Endpoint Committee(CEC).This adjudication was used for data analysis, and was not used to guide subject treatment.
Time frame: Baseline through Week 24
Period 1: Percentage of Participants Who Experience CW
Clinical worsening was defined as any of the following: death,lung or heart transplantation,atrial septostomy or Potts' shunt,hospitalization for Pulmonary Arterial Hypertension(PAH) progression,new onset syncope, initiation of new PAH therapy(including increase in the dose of existing PAH specific concomitant therapy,such as endothelin receptor agonist or beraprost medication),or increase of 1 or more in World Health Organization(WHO) Functional Class(except for participants already in Class IV; only for participants unable to perform the 6 minute walk(6MW) test;worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk(6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance(for those participants who are ≥6 years of age).Criteria for CW(from Period 1) were adjudicated by an independent,blinded study-specific Clinical Endpoint Committee(CEC).This adjudication was used for data analysis, and was not used to guide subject treatment.
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Children's Heathcare of Atlanta, Inc. at Egleston
Atlanta, Georgia, United States
Childrens Hospital of Michigan
Detroit, Michigan, United States
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, United States
Nationwide Children's Hosp
Columbus, Ohio, United States
Vanderbilt Univeristy School of Medicine
Nashville, Tennessee, United States
Texas Childrens Hospital
Houston, Texas, United States
Primary Childrens Medical Center
Salt Lake City, Utah, United States
AKH
Vienna, Austria
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, Belgium
Pronto Socorro Cardiologico de Pernambuco-PROCAPE
Recife, Pernambuco, Brazil
...and 33 more locations
Time frame: Baseline through Week 24
Period 1: Pharmacokinetics (PK): Apparent Clearance (CL/F) of Tadalafil at Steady-state
Period 1: Pharmacokinetics (PK): Apparent Clearance (CL/F) of Tadalafil at steady-state
Time frame: Week 2, Week 4, Week 16 and Week 24
Period 2: Percentage of Participants Who Experience CW
Clinical worsening was defined as any of the following: death, lung or heart transplantation, atrial septostomy or Potts' shunt, hospitalization for Pulmonary Arterial Hypertension (PAH) progression, new onset syncope, initiation of new PAH therapy (including increase in the dose of existing PAH specific concomitant therapy, such as endothelin receptor agonist or beraprost medication), or increase of 1 or more in World Health Organization(WHO) Functional Class (except for participants already in Class IV; only for participants unable to perform the 6 minute walk (6MW) test; worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk (6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance (for those participants who are ≥6 years of age).
Time frame: Period 2 Baseline through Study Completion (Up to 24 Months)
Period 2: Time to First Occurrence of CW
Clinical worsening was defined as any of the following: death, lung or heart transplantation, atrial septostomy or Potts' shunt, hospitalization for Pulmonary Arterial Hypertension (PAH) progression, new onset syncope, initiation of new PAH therapy (including increase in the dose of existing PAH specific concomitant therapy, such as endothelin receptor agonist or beraprost medication), or increase of 1 or more in World Health Organization(WHO) Functional Class (except for participants already in Class IV; only for participants unable to perform the 6 minute walk (6MW) test; worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk (6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance (for those participants who are ≥6 years of age).
Time frame: Period 2 Baseline through Study Completion (Up to 24 Months)