Study of Cicletanine for Pulmonary Arterial Hypertension (PAH)

NCT ID: NCT00832507

Last Updated: 2014-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2012-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cicletanine 150 mg QD

Cicletanine 150 mg administered once daily (QD)

Group Type EXPERIMENTAL

Cicletanine

Intervention Type DRUG

Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily

Cicletanine 150 mg BID

Cicletanine 150 mg administered twice daily (BID)

Group Type EXPERIMENTAL

Cicletanine

Intervention Type DRUG

Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily

Cicletanine 300 mg QD

Cicletanine 300 mg administered once daily (QD)

Group Type EXPERIMENTAL

Cicletanine

Intervention Type DRUG

Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily

Placebo

Placebo to match cicletanine administered once daily

Group Type PLACEBO_COMPARATOR

Cicletanine

Intervention Type DRUG

Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily

Cicletanine Placebo

Intervention Type DRUG

Placebo to match cicletanine administered orally once daily, followed by active cicletanine in the blinded extension period

Interventions

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Cicletanine

Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily

Intervention Type DRUG

Cicletanine Placebo

Placebo to match cicletanine administered orally once daily, followed by active cicletanine in the blinded extension period

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gennyne Walker, PhD

Role: STUDY_CHAIR

Senior Clinical Research Scientist, Gilead Sciences

Locations

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University of South Alabama

Mobile, Alabama, United States

Site Status

Arizona Pulmonary Specialists

Phoenix, Arizona, United States

Site Status

VA Greater LA Healthcare System

Los Angeles, California, United States

Site Status

University of California San Diego Medical Center

San Diego, California, United States

Site Status

Harish H. K. Murthy, MD

San Jose, California, United States

Site Status

UCLA Medical Center

Torrance, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

University of Connecticut Health Center

Farmington, Connecticut, United States

Site Status

Cleveland Clinic

Fort Lauderdale, Florida, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Medical College of Georgia

Augusta, Georgia, United States

Site Status

University of Chicago Hospital

Chicago, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Louisiana State University

New Orleans, Louisiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Tufts-New England Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Children's Hospital Boston

Boston, Massachusetts, United States

Site Status

Boston University School of Medicine

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Beth Israel Medical Center

New York, New York, United States

Site Status

Cornell University

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

New York Presbyterian Hospital

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

The Lindner Clinical Trial Center

Cincinnati, Ohio, United States

Site Status

Case Medical Center

Cleveland, Ohio, United States

Site Status

Davis Heart and Lung Research Institute

Columbus, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

University Of Virginia

Charlottesville, Virginia, United States

Site Status

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

University Klinik Graz

Graz, , Austria

Site Status

University Klinik Wien

Vienna, , Austria

Site Status

ULB Hôpital Erasme

Brussels, , Belgium

Site Status

Peter Lougheed Centre

Calgary, Alberta, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Ludwig-Maximilians-Universitaet

Munich, Bavaria, Germany

Site Status

Universitaetsklinikum Giessen und Marburg

Giessen, Hesse, Germany

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Unidad de Investigación Clínica en Medicina S.C.

Monterrey, Nuevo León, Mexico

Site Status

Instituto Nacional de Cardiologia Ignacio Chavez

Mexico City, , Mexico

Site Status

H Clinic i Provincial

Barcelona, , Spain

Site Status

HU 12 de Octubre

Madrid, , Spain

Site Status

Royal Free Hospital

London, Gt Lon, United Kingdom

Site Status

Countries

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

Other Identifiers

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GS-US-235-0101

Identifier Type: -

Identifier Source: org_study_id

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