Study of Cicletanine for Pulmonary Arterial Hypertension (PAH)

Pulmonary Arterial Hypertension Clinical Trial

Official title:

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-ranging Study of Cicletanine in Subjects With Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00832507
• Other study ID #: GS-US-235-0101
• Status: Terminated
• Phase: Phase 2
• First received: January 29, 2009
• Last updated: January 3, 2014
• Start date: January 2009
• Est. completion date: March 2012

Study information

• Verified date: January 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Federal Institute for Drugs and Medical DevicesIsrael: Ministry of HealthMexico: Ministry of HealthSpain: Ministry of Health and ConsumptionUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This Phase 2, randomized, double-blind, placebo-controlled, multicenter, dose-ranging study will compare the efficacy, safety, and tolerability of cicletanine hydrochloride (HCl) to placebo in subjects with PAH. Study drug will be administered alone, or on the background of stable PAH therapy. The study will consist of 3 periods: a screening period, a 12-week placebo-controlled treatment period, and a long-term, blinded extension period.

Description:

The primary objective of this study is to compare the change in exercise capacity following treatment with cicletanine HCl or placebo in subjects with PAH.

The secondary objectives of this study are:

1. To compare the change in other clinical measures of PAH following treatment with cicletanine HCl or placebo in subjects with PAH

2. To compare the safety and tolerability of cicletanine HCl to placebo in subjects with PAH Additionally, the long-term safety, tolerability, and efficacy of cicletanine HCl treatment will be evaluated.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 162
• Est. completion date: March 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Cicletanine
Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily
• Cicletanine Placebo
Placebo to match cicletanine administered orally once daily, followed by active cicletanine in the blinded extension period

Locations

Country	Name	City	State
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Austria	University Klinik Graz	Graz
Austria	University Klinik Wien	Wien
Belgium	ULB Hôpital Erasme	Bruxelles
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Germany	Universitaetsklinikum Giessen und Marburg	Giessen	HE
Germany	Ludwig-Maximilians-Universitaet	Muenchen	BY
Israel	Rabin Medical Center	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez	Mexico City
Mexico	Unidad de Investigación Clínica en Medicina S.C.	Monterrey	NL
Spain	H Clinic i Provincial	Barcelona
Spain	HU 12 de Octubre	Madrid
United Kingdom	Royal Free Hospital	London	Gt Lon
United States	Emory University	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts-New England Medical Center	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University Of Virginia	Charlottesville	Virginia
United States	University of Chicago Hospital	Chicago	Illinois
United States	The Lindner Clinical Trial Center	Cincinnati	Ohio
United States	Case Medical Center	Cleveland	Ohio
United States	Davis Heart and Lung Research Institute	Columbus	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Cleveland Clinic	Ft. Lauderdale	Florida
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	VA Greater LA Healthcare System	Los Angeles	California
United States	University of South Alabama	Mobile	Alabama
United States	Intermountain Medical Center	Murray	Utah
United States	Louisiana State University	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Cornell University	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York Presbyterian Hospital	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of California San Diego Medical Center	San Diego	California
United States	Harish H. K. Murthy, MD	San Jose	California
United States	Washington University School of Medicine	St. Louis	Missouri
United States	UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in six-minute walk distance (6MWD) evaluated after 12 weeks of treatment		Baseline to Week 12	No
Secondary	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.		Baseline to Week 60	Yes