Pulmonary Arterial HypertensionPhase 2NCT00832507
Study of Cicletanine for Pulmonary Arterial Hypertension (PAH)
A Phase 2 study testing Cicletanine in people with Pulmonary Arterial Hypertension, run by Gilead Sciences at 56 sites in 10 countries.
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. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Cicletanine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 162 participants
- Where
- 56 sitesin 10 countries
- Study dates
- Jan 2009to Mar 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
56 sites in 10 countries.
56 sites in 10 countries
United States39 sites
Emory University
Atlanta, Georgia, 30322
Medical College of Georgia
Augusta, Georgia, 30912
University of Colorado Denver
Aurora, Colorado, 80045
University of Maryland
Baltimore, Maryland, 21201
Tufts-New England Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital
Boston, Massachusetts, 02114
Children's Hospital Boston
Boston, Massachusetts, 02115
Boston University School of Medicine
Boston, Massachusetts, 02118
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
University Of Virginia
Charlottesville, Virginia, 22908
University of Chicago Hospital
Chicago, Illinois, 60637
The Lindner Clinical Trial Center
Cincinnati, Ohio, 45219
Case Medical Center
Cleveland, Ohio, 44106
Davis Heart and Lung Research Institute
Columbus, Ohio, 43210-1252
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
University of Connecticut Health Center
Farmington, Connecticut, 06030
Cleveland Clinic
Fort Lauderdale, Florida, 33331
University of Florida
Gainesville, Florida, 32610
Baylor College of Medicine
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
VA Greater LA Healthcare System
Los Angeles, California, 90073
University of South Alabama
Mobile, Alabama, 36617
Intermountain Medical Center
Murray, Utah, 84157
Louisiana State University
New Orleans, Louisiana, 70112
Beth Israel Medical Center
New York, New York, 10003
Cornell University
New York, New York, 10021
Mount Sinai Medical Center
New York, New York, 10029
New York Presbyterian Hospital
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Arizona Pulmonary Specialists
Phoenix, Arizona, 85013
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14623
University of California San Diego Medical Center
San Diego, California, 92037
Harish H. K. Murthy, MD
San Jose, California, 95124
Washington University School of Medicine
St Louis, Missouri, 63110
UCLA Medical Center
Torrance, California, 90502
Canada3 sites
Peter Lougheed Centre
Calgary, Alberta, T1Y6J4
London Health Sciences Centre
London, Ontario, N6A5W9
Jewish General Hospital
Montreal, Quebec, H3T1E2
Australia2 sites
St Vincent's Hospital
Darlinghurst, New South Wales, 2010
Royal Perth Hospital
Perth, Western Australia, 6001
Austria2 sites
University Klinik Graz
Graz, 8036
University Klinik Wien
Vienna, 1090
Germany2 sites
Universitaetsklinikum Giessen und Marburg
Giessen, Hesse, 35392
Ludwig-Maximilians-Universitaet
Munich, Bavaria, 80336
Israel2 sites
Rabin Medical Center
Petah Tikva, 49100
Chaim Sheba Medical Center
Ramat Gan, 52621
Mexico2 sites
Instituto Nacional de Cardiologia Ignacio Chavez
Mexico City
Unidad de Investigación Clínica en Medicina S.C.
Monterrey, Nuevo León, 64718
Spain2 sites
H Clinic i Provincial
Barcelona, 8036
HU 12 de Octubre
Madrid, 28041
About this study
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-ranging Study of Cicletanine in Subjects With Pulmonary Arterial Hypertension
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.
Read the detailed 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:
- To compare the change in other clinical measures of PAH following treatment with cicletanine HCl or placebo in subjects with PAH
- 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
- Pulmonary Arterial Hypertension
- Being tested
- Cicletanine, Cicletanine Placebo
- Keywords
- PAH, pulmonary hypertension, cicletanine, cicletanine HCL, cardiovascular, endothelin receptor antagonist, ERA, monotherapy, combination therapy, phosphodiesterase type-5 inhibitor, PDE5i, parenteral prostanoid, PH, pulmonary
- Medical subject headings
- Pulmonary Arterial Hypertension, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CicletanineDrug
Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily
Cicletanine PlaceboDrug
Placebo to match cicletanine administered orally once daily, followed by active cicletanine in the blinded extension period
| Study group | Role | What they receive |
|---|---|---|
| Cicletanine 150 mg QD | Experimental | Cicletanine 150 mg administered once daily (QD) Receives: Drug: Cicletanine |
| Cicletanine 150 mg BID | Experimental | Cicletanine 150 mg administered twice daily (BID) Receives: Drug: Cicletanine |
| Cicletanine 300 mg QD | Experimental | Cicletanine 300 mg administered once daily (QD) Receives: Drug: Cicletanine |
| Placebo | Placebo comparator | Placebo to match cicletanine administered once daily Receives: Drug: Cicletanine; Drug: Cicletanine Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in six-minute walk distance (6MWD) evaluated after 12 weeks of treatment
Measured: 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.
Measured: Baseline to Week 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionOct 2011
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 162 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gennyne Walker, PhD, Study chair, Senior Clinical Research Scientist, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00832507
- Sponsor's protocol ID
- GS-US-235-0101
- Status last verified
- Jan 2014
- First submitted
- 29 Jan 2009
- Last updated
- 4 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-ranging Study of Cicletanine in Subjects With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT00832507
- Acronym / sponsor ID
- GS-US-235-0101
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- PAH, pulmonary hypertension, cicletanine, cicletanine HCL, cardiovascular, endothelin receptor antagonist, ERA, monotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 162 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 30 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- To compare the change in other clinical measures of PAH following treatment with cicletanine HCl or placebo in subjects with PAH
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cicletanine 150 mg QD | Experimental | Drug: CicletanineCicletanine 150 mg administered once daily (QD) |
| Cicletanine 150 mg BID | Experimental | Drug: CicletanineCicletanine 150 mg administered twice daily (BID) |
| Cicletanine 300 mg QD | Experimental | Drug: CicletanineCicletanine 300 mg administered once daily (QD) |
| Placebo | Placebo comparator | Drug: Cicletanine, Drug: Cicletanine PlaceboPlacebo to match cicletanine administered once daily |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CicletanineCicletanine capsules 150 mg or 300 mg administered orally once or twice daily | Drug | Cicletanine 150 mg BID, Cicletanine 150 mg QD, Cicletanine 300 mg QD, Placebo |
| Cicletanine PlaceboPlacebo to match cicletanine administered orally once daily, followed by active cicletanine in the blinded extension period | Drug | Placebo |
Primary outcome
Change from baseline in six-minute walk distance (6MWD) evaluated after 12 weeks of treatment
Time frame: Baseline to Week 12
1 secondary outcome
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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gennyne Walker, PhD study chair
Senior Clinical Research Scientist, Gilead Sciences
56 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cicletanine in people with Pulmonary Arterial Hypertension, run by Gilead Sciences at 56 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, Canada, Australia, Austria, Germany and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in six-minute walk distance (6MWD) evaluated after 12 weeks of treatment (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2014.