Pulmonary Arterial Hypertension MedDRA version: 9.0 Level: LLT Classification code 10064911
Conditions
Interventions
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sildenafil (as citrate)
CAS Number: N/A
Other descriptive name: UK-92,480
C
Sponsors
Pfizer Ltd, Ramsgate Rd, Sandwich, Kent, United Kingdom
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female subjects aged from 1 to 17 years old. Females of child bearing potential who are sexually active must be practicing a suitable method of birth control so that in the opinion of the investigator, they will not become pregnant during the study; • Subjects weighing =8 kg; • Subjects who have symptomatic pulmonary arterial hypertension due to one of the following conditions: • Primary pulmonary hypertension; • Pulmonary arterial hypertension in the presence of a small or hemodynamically insignificant congenital systemic to pulmonary shunt lesion that in the opinion of the investigator is not the cause of pulmonary hypertension; • Pulmonary arterial hypertension associated with collagen vascular disease (e.g., scleroderma); • Pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts with a baseline resting room air oxygen saturation =88%. If the defect(s) is repaired, it should have been repaired at least 6 months prior to screening. Note: Repairs can be either surgical or via interventional cardiac catheterization (eg, ASD closure device or coil of PDA); • Pulmonary arterial hypertension associated with d-transposition of the great arteries repaired within the first 30 days of life; or • Pulmonary arterial hypertension in subjects who have undergone surgical repair of other congenital heart lesions at least 6 months prior to screening and do not have clinically significant residual left-sided heart disease consistent with the exclusion criteria • Subjects with a mean pulmonary artery pressure =25 mmHg at rest, PCWP =15 mmHg, and PVRI =3 Wood units x m2. If PCWP is not available, then mean LA pressure =15 mmHg or LVEDP =15 mmHg in the absence of left atrial obstruction; Note: Hemodynamic measurements can be performed within 21 days prior to randomization for study purposes. These criteria must be within specified baseline limits for subject to qualify for randomization. Hemodynamic measurements from the retrospective right heart catheterization may be used for qualification provided the subject’s background therapy (class of drug) for PAH did not change for the 10 days prior to the procedure, and has not changed since the procedure was performed. • Subjects, developmentally able to exercise, whose CPX exercise test functional capacity is within the following parameters: Peak VO2 =10 mL/kg/min and =28 mL/kg/min during screening CPX test; • The investigator must obtain written informed consent and assent where applicable before the subject is screened for the study. The inclusion of a subject more than once in the same clinical trial is not permissible; and • Subjects who undergo a large shift in altitude in order to participate in the study (e.g.live at altitude and shift to sea level in order to participate) must reside at the “in study” altitude for at least 90 days prior to baseline and during the study period. Note: A “large shift is being defined as approximately 5000 feet or 1524 meters. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of sub
Exclusion criteria
Exclusion criteria: • Subjects with pulmonary hypertension secondary to sickle cell disease, any other disease known to be associated with PAH, or any etiology other than those specified in the inclusion criteria; Left-sided heart disease, including any of the following: • Aortic or mitral valve disease (greater than mild); • Restrictive or congestive cardiomyopathy; • PCWP or LVEDP > 15mmHg; • LVEF 2.5 × ULN ) or hepatic function (ALT and/or AST >3 × ULN; and/or bilirubin =2 mg/dL). Hematological abnormalities (e.g., severe anemia, Hgb 2 × ULN; Subjects with any medical condition which in the opinion of the investigator may interfere with treatment, evaluation of safety, and/or efficacy. Abnormalities of questionable clinical significance must be discussed with a Pfizer clinician prior to inclusion of the subject; Change in class of medication for CHF or PAH within the 10 days prior to qualifying right heart catheterization. (Note: Discontinuation of coumadin, start of heparin, and the re-starting of coumadin for cardiac catheterization is not considered change in dose or class.); Subjects who are currently prescribed and/or taking nitrates or nitric oxide donors in any form (oral, sublingual, buccal, transdermal, inhalational or aerosols). Acute vasodilator testing with nitric oxide is permitted during hemodynamic evaluation; Subjects taking chronic arginine supplementation including Heart Bar®; Subjects w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of 16 weeks of chronic treatment with oral sildenafil in pediatric subjects, aged 1 to 17 years, with PAH. Primary efficacy will be measured by exercise tolerance, bicycle ergometry testing in those subjects who are developmentally able to perform the exercise paradigm as described in the protocol. Secondary efficacy will be assessed in all subjects as described in Section 6.4.1.2 of the protocol.; Secondary Objective: To assess safety, tolerability, and pharmacokinetics of 16 weeks of chronic treatment with oral sildenafil in pediatric subjects, aged 1 to 17 years with PAH. To assess the survival status of subjects who have discontinued study drug. ;Primary end point(s): Percent change in peak VO2 normalised to body weight from baseline to Week 16 assessed by CPX testing (bicycle ergometry). As described previously, this endpoint will be evaluated in those subjects who are developmentally able to perform the CPX test. | — |
Countries
Finland, Slovakia, United Kingdom
Outcome results
None listed