Iloprost Power Disc-15 in Pulmonary Arterial Hypertension (INHALE-15)

Actelion Pharmaceuticals

Status and phase: Terminated; Phase 3

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Iloprost PD-15; Drug: Iloprost PD-6

Study type: Interventional

Funder types: Industry

Identifiers

NCT00723554

AC-063A402

Details and patient eligibility

About

A Phase IIIb, Multicenter, Open-Label Study of Patients With Pulmonary Arterial Hypertension Treated With Iloprost(Inhalation)Evaluating Safety and Inhalation Times When Converting From Power Disc-6 to Power Disc-15 With the I-neb® Adaptive Aerosol Delivery® System (I-neb® AAD®)

Enrollment: 63 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent prior to initiation of any study-mandated procedure.

• Male or female patients aged 18-85 years.

• Patients with symptomatic pulmonary arterial hypertension in New York Heart Association (NYHA) functional class III or IV at the time of initiation of iloprost inhalation (Ventavis®) therapy using the Power Disc-6 (PD-6).

• Patients with the following types of pulmonary arterial hypertension (PAH) belonging to World Health Organization (WHO) Group I:

  • 1.1: Idiopathic (IPAH)

  • 1.2: Familial (FPAH)

  • 1.3: Associated with (APAH)

    • 1.3.1: Collagen vascular disease
    • 1.3.2: Congenital systemic-to-pulmonary shunts at least 2 years post surgical repair
    • 1.3.4: Human immunodeficiency virus (HIV) infection
    • 1.3.5: Drugs and toxins

• PAH confirmed by the most recent right heart catheterization showing:

  • Mean pulmonary arterial pressure (mPAP)≥ 25 mmHg at rest
  • Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg. If both PCWP and LVEDP are available then the LVEDP value is retained for inclusion.
  • Pulmonary vascular resistance (PVR) > 240 dyn-sec/cm^5

• Compliant with a treatment regimen of commercial iloprost inhalation (Ventavis® 5 μg) using the I-neb® AAD® equipped with the PD-6 for at least 4 weeks prior to screening.

• Pulmonary function tests (PFTs) including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and total lung capacity (TLC), performed within 6 months of screening.

• If taking other medications for PAH, these must have been stable for 60 days prior to baseline.

• If taking corticosteroids, these must have been stable for 60 days prior to baseline.

• Women of childbearing potential with a negative urine pre-treatment pregnancy test at baseline and who:

  • consistently and correctly use (from screening and up to 28 days after discontinuation of study drug) a reliable method of contraception with a Pearl index of < 1%,
  • are sexually abstinent, or
  • have a vasectomized partner.

A woman is considered to have childbearing potential unless she meets at least one of the following criteria:

• Previous bilateral salpingo-oophorectomy or hysterectomy
• Premature ovarian failure confirmed by a specialist gynecologist
• XY genotype, Turner syndrome, uterine agenesis
• Is aged > 50 years and not treated with any kind of hormone replacement therapy (HRT) for at least 2 years prior to screening, with amenorrhea for at least 24 consecutive months

Exclusion criteria

• PAH belonging to WHO group II-V.

• PAH belonging to WHO group I other than that listed in the inclusion criteria, i.e., PAH associated with:

  • 1.3.3: Portal hypertension

  • 1.3.6: Other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy)

  • 1.4: Associated with significant venous or capillary involvement:

    • 1.4.1: Pulmonary veno-occlusive disease (PVOD)
    • 1.4.2: Pulmonary capillary hemangiomatosis (PCH).

• Receipt of any prostacyclin or prostacyclin analog other than iloprost within 12 weeks before screening.

• Anticipation of the need for intravenous prostacyclin use within 28 days of starting the Power Disc-15 (PD-15).

• HIV-seropositive with any of the following:

  • Concomitant active opportunistic infections within 6 months prior to screening
  • Detectable viral load within 6 months of screening
  • CD4+ T-cell count < 200 mm^3 within 3 months of screening
  • Changes in antiretroviral regimen within 3 months of screening
  • Anticipated changes in antiretroviral regimen during study periods 1 or 2
  • Using inhaled pentamidine

• Systemic hypotension with systolic blood pressure < 95 mmHg.

• Uncontrolled systemic hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg on repeated measurement).

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

  • hemodynamically significant aortic or mitral valve disease
  • restrictive or congestive cardiomyopathy
  • left ventricular ejection fraction < 40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography
  • coronary artery disease with continuing symptoms of angina pectoris
  • life-threatening cardiac arrhythmias

• Atrial septostomy within 1 year.

• History of pulmonary embolism prior to diagnosis of PAH unless it can be documented that chronic thromboembolic pulmonary hypertension (CTEPH) has been specifically excluded (e.g., ventilation/perfusion (VQ) scan, pulmonary angiogram).

• Restrictive lung disease: TLC < 60% of normal predicted value.

• Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) < 0.5 or clinically relevant chronic obstructive lung disease or asthma (including any patient requiring concomitant medication to control symptoms of bronchospasm including as needed (p.r.n.) use).

• Clinically relevant bleeding disorder or active bleeding.

• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C or hepatic cirrhosis.

• Pregnant or breast-feeding.

• Chronic renal insufficiency, as defined by a creatinine of > 2.5 mg/dL or the requirement for dialysis.

• Hemoglobin < 75% of the lower limit of normal range.

• Any condition that prevents compliance with the protocol or adherence to therapy or ability to provide informed consent.

• Participation in any other clinical trial, except observational, or receipt of an investigational product within 30 days prior to enrollment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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63 participants in 1 patient group

Iloprost

Experimental group

Description:

The study enrolled patients who were already using iloprost with PD-6 without any safety or tolerability concerns, thereby facilitating a direct comparison of the PD-15 to the PD-6. The single-arm design allowed each patient to serve as his/her own control

Treatment:

Drug: Iloprost PD-6

Drug: Iloprost PD-15