Double-blind, randomized, placebo-controlled, dose-finding, parallel-group study to assess the hemodynamic effects, clinical efficacy, tolerability and safety of Aviptadil (Vasoactive Intestinal Peptide) after single and repeated inhalation in patients with pulmonary arterial hypertension.

• Conditions: Pulmonary arterial hypertension (PAH) due to idiopathic pulmonary arterial hypertension (IPAH), familial PAH or PAH associated with connective tissue diseases (CTD) (e.g. systemic sclerosis, systemic lupus erythematosus) or to repaired congenital heart defects (RCHD).; MedDRA version: 9.1Level: LLTClassification code 10064911Term: Pulmonary arterial hypertension; MedDRA version: 9.1Level: LLTClassification code 10065151Term: Idiopathic pulmonary arterial hypertension; MedDRA version: 9.1Level: LLTClassification code 10065152Term: Familial pulmonary arterial hypertension; MedDRA version: 9.1Level: LLTClassification code 10065150Term: Associated with pulmonary arterial hypertension

• Registration Number: EUCTR2007-003621-24-NL
• Lead Sponsor: MondoGEN AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-13
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

To be eligible for admission to the study, the following criteria must be met:
1. Male and female patients between 18 and 80 years of age with IPAH, familial PAH or PAH
associated with CTD or RCHD.
2. Patients with NYHA/WHO functional class II or III.
3. Patients who have received stabilized therapy (i.e., therapy with [a] stable dose[s]) with an endothelin receptor antagonist approved for the treatment of PAH or a phosphodiesterase type 5 inhibitor approved for the treatment of PAH or a combination of both for at least 4 months prior to screening.
4. Symptomatic PAH diagnosed as either IPAH, familial PAH or PAH associated with CTD or RCHD clinically stable for at least 1 month prior to the inclusion.
5. An unencouraged 6-MWT of more than 200 meters but less than 550 meters at screening.
6. Prior cardiac catheterization consistent with PAH, specifically mean pulmonary arterial pressure (PAPm) > 25 mmHg (at rest), PCWP (or left ventricular end diastolic pressure) = 15 mmHg and PVR > 3 mmHg/L/min.
7. Echocardiogram data acquired within 12 months prior to study drug administration that are consistent with PAH, specifically evidence of right ventricular hypertrophy or dilation, evidence of normal left ventricular function, and absence of mitral valve stenosis.
8. Chest radiograph or CT angiography consistent with the diagnosis of PAH generated within 12 months prior to study drug administration.
9. Able to understand and willing to sign the Informed Consent Form.
10. Results of pulmonary function tests (within the last 6 months) as follows: total lung capacity = 60% predicted and forced expiratory volume in 1 second/forced vital capacity = 50% predicted.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A patient may not enter the trial if any of the following criteria apply:
1. Patients with NYHA/WHO functional class I or IV.
2. Patients with PAH due to conditions other than IPAH, familial PAH or PAH associated with CTD or RCHD.
3. Patients who are on therapy with prostanoids, endothelin receptor antagonists not approved for the treatment of PAH or phosphodiesterase type 5 inhibitors not approved for the treatment of PAH. Note: Calcium channel blockers can be given according to the judgement of the Investigator and are not limited to a certain substance or dose.
4. Patients with Eisenmenger’s Syndrome (a condition where the patient has a septal defect of the heart or a persistent ductus arteriosus and where resulting pulmonary hypertension creates a reversal of the shunt).
5. Patients who have a new type of chronic therapy (e.g. a different category of vasodilator, diuretic) for PAH added within the last month, except anticoagulants.
6. Patients who have received therapy with an investigational drug within 3 months prior to the start of this study or who are scheduled to receive another investigational drug during the course of this study.
7. Patients who have discontinued regular medication or who have changed dose or class of any medication within the last week, except anticoagulants or insulin.
8. Patients with a concomitant disease that could interfere with their ability to perform the 6-MWT.
9. Patients with an acute concomitant disease that could potentially complicate the assessment of PAH disease severity or response to therapeutic intervention.
10. Patients with any illness other than PAH which might reduce life expectancy to less than 6 months.
11. Patients incapable or unwilling to sign the informed consent.
12. Patients pregnant and/or lactating. Females who plan to become pregnant during the study and females who are not using a highly effective method of birth control (failure rate less than 1% per year).
13. Patients with any pre-existing disease known to cause pulmonary hypertension unless listed in the inclusion criteria. The following pre-existing diseases are exclusionary: obstructive lung disease, parasitic disease affecting the pulmonary system, sickle cell anemia, mitral valve stenosis, portal hypertension and HIV infection.
14. Patients with a history of drug and/or alcohol abuse, as defined by the Investigator.
15. Patients with PAH associated with repaired congenital heart disease, who underwent the corrective surgery within 12 months prior to screening.
16. Patients taking prednisone at a dose higher than 20 mg/day.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to assess the efficacy of a number of doses of Aviptadil acutely and after 12 weeks of treatment.;Secondary Objective: The secondary objective of the study is to assess the safety and tolerability of a number of doses of Aviptadil.;Primary end point(s): The primary endpoint of this study is the percentage change in PVR (peak PVR reduction compared to baseline PVR) after a single Aviptadil inhalation on Day 2, where baseline PVR is defined as the value measured when stability is reached prior to first investigational product inhalation at baseline (Base 2) and peak PVR is defined as the lowest value of PVR in post-baseline assessments (at 15,<br>30, 45, 60, 90, 120, 150 or 180 minutes).