A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging Study of Cicletanine in Subjects with Pulmonary Arterial Hypertension

Study Status

Open to Enrollment

Study Description

The purpose of this study is to compare the change in exercise capacity in patients with pulmonary arterial hypertension after treatment with cicletanine HCI or placebo..

Screening Period: Subjects will be screened within four weeks of the initial visit.

12-Week Treatment Period: Eligible subjects will be grouped according to the type of PAH with which they've been diagnosed (i.e., Idiopathic PAH, Familial PAH or other PAH) and whether or not they've previously received treatment with a prostanoid. Subjects will then be randomized into four groups: those receiving a placebo; those receiving 150 mg cicletanine HCI once daily; those receiving 150 mg cicletanine HCI twice daily; and those receiving 300 mg cicletanine HCI once daily. Subjects in the three groups receiving cicletanine HCI will be given half the study dose for the first two weeks of the study, then the full study dose for the remaining 10 weeks. In the event of intolerance to cicletanine HCI, the investigator may decrease the subject's dose by half. If the subject tolerates the lower dose, the investigator may gradually re-increase the dose, up to the original level. All subjects who are receiving cicletanine HCI in combination with another, pre-prescribed PAH therapy must remain constant with the pre-prescribed therapy for the duration of the study.

Due to the placebo-controlled design of the study, there is a one out of four chance that a subject will not receive cicletanine HCI during the course of the study. After a minimum treatment period of four weeks, subjects in the placebo group who meet certain criteria may end their participation in the study. Subjects in the placebo group may be eligible to initiate active treatment with cicletanine HCI during the long-term extension period of this study.

Various clinical and laboratory evaluations will be conducted during subject visits.

Long-Term, Blinded Extension Period: Subjects who received cicletanine HCI during the 12-week treatment period will be eligible to continue long-term treatment at their current dose. Subjects in the placebo group during the first 12 weeks will be eligible for long-term treatment, and those who elect long-term treatment will be randomized into one of the three cicletanine HCI dose groups.

Clinical and laboratory evaluations will be conducted at various visits throughout the extension period. Subjects may continue treatment with cicletanine HCI until such time as the investigator or subject chooses to stop treatment, the cumulative data analysis does not warrant continuation of the study, or the sponsor ends the study. The study will run for a maximum of seven years.

Sponsor

Gilead Sciences

Key Eligibility

Inclusion criteria:

  • Between 19 and 65 years of age
  • Weight ≥ 40 kg (88 lbs)
  • Have a current diagnosis of idiopathic pulmonary arterial hypertension (PAH), familial PAH or PAH that is primarily due to: connective tissue disease, congenital heart defects, drug and toxin use or HIV infection
  • Those receiving another, pre-prescribed treatment for PAH must meet certain criteria (study coordinators will provide further detail)
  • Subject receiving diuretic treatment must be on stable therapy
  • If receiving Digitalis, CCBs, angiotensin receptor blockers (ARBs), angiotensin converting enzyme (ACE) inhibitors or beta-blocking agents, subject must be on stable therapy
  • If receiving HMG-CoA reductase inhibitors, subject must be on stable therapy
  • If diagnosis of HIV, subject must have stable disease status
  • Has not enrolled in an exercise training program for pulmonary rehabilitation and must agree not to enroll in one
  • If subject has been enrolled in an exercise training program for pulmonary rehabilitation for greater than 12 weeks prior to the Screening visit, he/she must agree to maintain the current level of rehabilitation for the first 12 weeks of the study
  • Additional criteria will be measured during the Screening Visit by means of tests including, but not limited to: right-heart catheterization, distance walking test, pulmonary function tests
Exclusion criteria:
  • Receiving intravenous inotropes within two weeks prior to the Screening visit
  • Moderate to severe liver disease or kidney impairment
  • Receiving lithium within two weeks prior to the Screening visit
  • Receiving intermittent or chronic treatment with nitrates
  • Receiving non-antiarrhythmic drugs
  • Diagnosis of long QT syndrome
  • Evidence of chronic thromboembolic disease
  • Obstructive lung disease
  • Severe arthritis, musculoskeletal problems or morbid obesity that would affect the subject's ability to perform or complete the six-minute walking test
  • History of malignancies within the past five years
  • Pregnant or breastfeeding
  • Recent history of abusing alcohol or illegal drugs
  • Participation in a clinical study involving another investigational drug or device within 12 weeks before the Screening visit
  • Receiving an oral arginine supplement within two weeks prior to the Screening visit

Principal Investigator

Evelyn M. Horn, MD

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For general inquiries, or if you need assistance finding a study, please contact:

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Subject Recruitment Manager
Tel: (646) 962-9340
[email protected]

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