A Pharmacokinetics Study for Pediatric Participants With Pulmonary Arterial Hypertension

Lilly

Status and phase: Completed; Phase 2; Phase 1

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Tadalafil- Tablet or Oral suspension

Study type: Interventional

Funder types: Industry

Identifiers

NCT01484431

H6D-MC-LVIG (Other Identifier)

12917

Details and patient eligibility

About

The purpose of this study is to see how much study drug is in the blood of children with pulmonary arterial hypertension (PAH) after dosing to establish the correct dose for further clinical research.

Full description

During Period I, tadalafil will be administered orally, once daily, at a low dose for approximately 5 weeks followed by a high dose for approximately 5 weeks. Dose levels are calculated based on body weight cohorts. Heavy weight cohort >=40 kg, middle weight cohort >=25 kg to <40 kg. Light weight cohort<25 kg. Participants who complete Period 1 may continue taking tadalafil in Period 2 for at least 2 years. Starting dose will not exceed the maximum weight range dose established in Period 1 and after the first 3 months of Period 2, the dose may be adjusted based on available safety and efficacy information.

Enrollment: 20 patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Currently have a diagnosis of PAH that is either:

  • idiopathic (including hereditary), related to collagen vascular disease, related to anorexigen use, associated with surgical repair, of at least 6 month duration, of a congenital systemic to pulmonary shunt (for example, atrial septal defect, ventricular septal defect, patent ductus arteriosus).

• Have a history of the diagnosis of PAH established by a resting mean pulmonary artery pressure ≥25 mm Hg, pulmonary artery wedge pressure ≤15 mm Hg, and a pulmonary vascular resistance (PVR) ≥3 Wood units via right heart catheterization. In the event that a pulmonary artery wedge pressure is unable to be obtained during right heart catheterization, participants with a left ventricular end diastolic pressure <15 mm Hg, with normal left heart function, and absence of mitral stenosis on echocardiography can be eligible for enrollment

• Have a World Health Organization (WHO) functional class value of I, II or III at the time of enrollment

Exclusion criteria

• Have pulmonary hypertension related to conditions other than specified above, including but not limited to chronic thromboembolic disease, portal pulmonary hypertension, left-sided heart disease or lung disease and hypoxia

• History of left-sided heart disease, including any of the following:

  • clinically significant (pulmonary artery occlusion pressure [PAOP] 15 to 18 mm Hg) aortic or mitral valve disease (that is, aortic stenosis, aortic insufficiency, mitral stenosis, moderate or greater mitral regurgitation)
  • pericardial constriction
  • restrictive or congestive cardiomyopathy
  • left ventricular ejection fraction <40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography
  • left ventricular shortening fraction <22% by echocardiography
  • life-threatening cardiac arrhythmias
  • symptomatic coronary artery disease within 5 years of study entry as determined by the physician

• History of atrial septostomy or Potts Shunt within 3 months before administration of study drug

• Unrepaired congenital heart disease

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

Tadalafil

Experimental group

Description:

Light Weight \<25 kg Period 1: 2 milligram (mg) or 4 mg tadalafil administered once daily (QD) in oral suspension formulation for 5 weeks then 8 mg,10 mg,15 mg or 20 mg tadalafil was administered QD in oral suspension formulation for 5 weeks. Middle Weight: 25 kg to \<40 kg Period 1: 5 mg tadalafil tablet administered QD for 5 weeks then 10 mg, 15 mg or 20 mg tablet tadalafil administered QD for 5 weeks. Heavy: ≥40 kg Period 1: 10 mg tadalafil tablet administered QD for 5 weeks then 20 mg or 40 mg tablet tadalafil administered QD for 5 weeks.

Treatment:

Drug: Tadalafil- Tablet or Oral suspension