Study of Cicletanine for Pulmonary Arterial Hypertension (PAH)

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00832507
• Date of registration: 29/01/2009
• Prospective Registration: No
• Primary sponsor: Gilead Sciences
• Public title: Study of Cicletanine for Pulmonary Arterial Hypertension (PAH)
• Scientific title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-ranging Study of Cicletanine in Subjects With Pulmonary Arterial Hypertension
• Date of first enrolment: January 2009
• Target sample size: 162
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00832507
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Australia, Austria, Belgium, Canada, Germany, Israel, Mexico, Spain, United Kingdom, United States

Contacts

• Name: Gennyne Walker, PhD
• Affiliation: Senior Clinical Research Scientist, Gilead Sciences

Key inclusion & exclusion criteria

Inclusion Criteria

- Between 16 and 70 years of age

- Weigh greater than or equal to 40 kg

- Have a current diagnosis of IPAH, FPAH, or PAH that is primarily due to: connective
tissue disease, congenital heart defects, drug and toxin use, and HIV infection

- Meet all of the following hemodynamic criteria by means of a RHC completed prior to
or during Screening: mPAP of greater than or equal to 25 mmHg, PVR greater than 240
dyne.sec/cm5, PCWP or LVEDP of less than or equal to1 5 mmHg

- Walk a distance of at least 100 m but no more than 450 m during the screening 6MWT

- Have WHO functional class II, III, or IV symptoms

- Meet all of the following pulmonary function tests completed no more than 12 weeks
before the Screening visit: TLC greater than or equal to 60% of predicted normal &
FEV1 greater than or equal to 65% of predicted normal, FEV1:FVC ratio greater than
0.60

- Have laboratory results within 90% of the lower limit of normal to 1.5 times the
upper limit of normal

- Receiving treatment with an approved ERA, PDE5i, and/or parenteral prostanoid must be
receiving this therapy for greater than or equal to 12 weeks prior to the Screening
Visit and must be at a stable dose for greater than or equal to 4 consecutive weeks
prior to the Screening Visit.

- Eligible therapies allowed at Screening include:a. Monotherapy with an ERA, PDE5i, or
parenteral prostanoid that is approved for the treatment of PAH b. Combination
therapy with two eligible PAH treatments (any combination of ERA, PDE5i, or
parenteral prostanoid

- 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

- Female subjects of childbearing potential must have a negative serum pregnancy test

- Female subjects of childbearing potential must agree to use 2 reliable methods of
contraception

- Must agree not to participate in a clinical study involving another investigational
drug or device

- Must be competent to understand and sign the IRB approved ICF

- Has not enrolled in an exercise training program for pulmonary rehabilitation and
must agree not to enroll in an exercise training program for pulmonary rehabilitation

- If subject has been enrolled in an exercise training program for pulmonary
rehabilitation for greater than 12 weeks prior to the Screening Visit and must agree
to maintain their current level of rehabilitation for the first 12 weeks of the study

- Must be on background PAH therapy at Screening unless the subject does not have
access to or can not tolerate currently approved PAH medical therapies

Exclusion Criteria

- Subject with a current PH diagnosis other than IPAH, FPAH, or PAH that is primarily
due to: Connective tissue disease, Congenital heart defects, Drug and toxin use, or
HIV infection

- Subject with LVEF less than or equal to 40% or clinically significant ischemic,
valvular, or constrictive heart disease

- Subject with WHO functional class I symptoms

- Subject has chronically received an ineligible PAH treatment regimen within the 4
weeks prior to the Screening Visit, specifically: a. inhaled iloprost or inhaled
treprostinil, b. combination treatment with three PAH therapies, c.any
investigational therapy for the treatment of PAH d.Chronic use is considered greater
than 7 consecutive days of treatment

- Subject receiving iv inotropes within 2 weeks prior to the Screening Visit

- Subject with SBP greater than or equal to 150 mmHg or less than 90mmHg

- Subject with moderate to severe liver disease

- Subject with moderate or severe renal impairment

- Subject receiving lithium within the 2 weeks prior to the Screening Visit

- Subject requiring intermittent or chronic treatment with nitrates

- Subject receiving non-anti-arrhythmic drugs

- Subject has a diagnosis of long QT syndrome

- Subject with evidence of chronic thromboembolic disease

- Subject with obstructive lung disease

- Subject with severe arthritis, musculoskeletal problems, or morbid obesity that would
affect the subject's ability to perform or complete the 6MWT

- Has a history of malignancies within the past 5 years

- Subject with disease that may adversely affect the safety of the subject and/or
efficacy of the study drug or severely limit the lifespan of the subject

- Female subject who is pregnant or breastfeeding

- Has demonstrated noncompliance with previous medical regimens

- Has a recent history of abusing alcohol or illicit drugs

- Has participated in a clinical study involving another investigational drug or device
within 4 weeks before the Screening Visit

- Has a known hypersensitivity to the study drug, the metabolites, or formulation
excipients

- Receiving an oral arginine supplement within 2 weeks prior to the Screening Visit



Age minimum: 16 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Cicletanine

Drug: Cicletanine Placebo

Primary Outcome(s)

Change from baseline in six-minute walk distance (6MWD) evaluated after 12 weeks of treatment [Time Frame: Baseline to Week 12]

Secondary Outcome(s)

Change from baseline in BDI, WHO Functional Class, BNP, cardiac hemodynamics and SF-36 physical functioning scale following 12 weeks of treatment. In addition, time to clinical worsening (TTCW) will be evaluated. [Time Frame: Baseline to Week 60]

Secondary ID(s)

GS-US-235-0101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors