NCT00832507

Brief 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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
162

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2009

Typical duration for phase_2

Geographic Reach
9 countries

54 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2009

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

January 29, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 30, 2009

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2011

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2012

Completed
Last Updated

February 4, 2014

Status Verified

January 1, 2014

Enrollment Period

2.7 years

First QC Date

January 29, 2009

Last Update Submit

January 3, 2014

Conditions

Keywords

PAHpulmonary hypertensioncicletaninecicletanine HCLcardiovascularendothelin receptor antagonistERAmonotherapycombination therapyphosphodiesterase type-5 inhibitorPDE5iparenteral prostanoidPHpulmonary

Outcome Measures

Primary Outcomes (1)

  • Change from baseline in six-minute walk distance (6MWD) evaluated after 12 weeks of treatment

    Baseline to Week 12

Secondary Outcomes (1)

  • 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

Study Arms (4)

Cicletanine 150 mg QD

EXPERIMENTAL

Cicletanine 150 mg administered once daily (QD)

Drug: Cicletanine

Cicletanine 150 mg BID

EXPERIMENTAL

Cicletanine 150 mg administered twice daily (BID)

Drug: Cicletanine

Cicletanine 300 mg QD

EXPERIMENTAL

Cicletanine 300 mg administered once daily (QD)

Drug: Cicletanine

Placebo

PLACEBO COMPARATOR

Placebo to match cicletanine administered once daily

Drug: CicletanineDrug: Cicletanine Placebo

Interventions

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

Cicletanine 150 mg BIDCicletanine 150 mg QDCicletanine 300 mg QDPlacebo

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

Placebo

Eligibility Criteria

Age16 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +6 more criteria

You may not qualify if:

  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (56)

University of South Alabama

Mobile, Alabama, 36617, United States

Location

Arizona Pulmonary Specialists

Phoenix, Arizona, 85013, United States

Location

VA Greater LA Healthcare System

Los Angeles, California, 90073, United States

Location

University of California San Diego Medical Center

San Diego, California, 92037, United States

Location

Harish H. K. Murthy, MD

San Jose, California, 95124, United States

Location

UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Cleveland Clinic

Fort Lauderdale, Florida, 33331, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Louisiana State University

New Orleans, Louisiana, 70112, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Tufts-New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Cornell University

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

New York Presbyterian Hospital

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14623, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

The Lindner Clinical Trial Center

Cincinnati, Ohio, 45219, United States

Location

Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Davis Heart and Lung Research Institute

Columbus, Ohio, 43210-1252, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

University Of Virginia

Charlottesville, Virginia, 22908, United States

Location

St Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6001, Australia

Location

University Klinik Graz

Graz, 8036, Austria

Location

University Klinik Wien

Vienna, 1090, Austria

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y6J4, Canada

Location

London Health Sciences Centre

London, Ontario, N6A5W9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Ludwig-Maximilians-Universitaet

Munich, Bavaria, 80336, Germany

Location

Universitaetsklinikum Giessen und Marburg

Giessen, Hesse, 35392, Germany

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Unidad de Investigación Clínica en Medicina S.C.

Monterrey, Nuevo León, 64718, Mexico

Location

Instituto Nacional de Cardiologia Ignacio Chavez

Mexico City, Mexico

Location

H Clinic i Provincial

Barcelona, 8036, Spain

Location

HU 12 de Octubre

Madrid, 28041, Spain

Location

Royal Free Hospital

London, Gt Lon, NW32QG, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Arterial HypertensionHypertension, Pulmonary

Interventions

cicletanine

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesHypertensionVascular DiseasesCardiovascular Diseases

Study Officials

  • Gennyne Walker, PhD

    Senior Clinical Research Scientist, Gilead Sciences

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 29, 2009

First Posted

January 30, 2009

Study Start

January 1, 2009

Primary Completion

October 1, 2011

Study Completion

March 1, 2012

Last Updated

February 4, 2014

Record last verified: 2014-01

Locations