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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00832507




Registration number
NCT00832507
Ethics application status
Date submitted
29/01/2009
Date registered
30/01/2009
Date last updated
4/02/2014

Titles & IDs
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
Secondary ID [1] 0 0
GS-US-235-0101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cicletanine
Treatment: Drugs - Cicletanine Placebo

Experimental: Cicletanine 150 mg QD - Cicletanine 150 mg administered once daily (QD)

Experimental: Cicletanine 150 mg BID - Cicletanine 150 mg administered twice daily (BID)

Experimental: Cicletanine 300 mg QD - Cicletanine 300 mg administered once daily (QD)

Placebo Comparator: Placebo - Placebo to match cicletanine administered once daily


Treatment: Drugs: Cicletanine
Cicletanine capsules 150 mg or 300 mg administered orally once or twice daily

Treatment: Drugs: Cicletanine Placebo
Placebo to match cicletanine administered orally once daily, followed by active cicletanine in the blinded extension period
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in six-minute walk distance (6MWD) evaluated after 12 weeks of treatment
Timepoint [1] 0 0
Baseline to Week 12
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to Week 60

Eligibility
Key inclusion 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
Minimum age
16 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2012
Sample size
Target
Accrual to date
Final
162
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Rhode Island
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
Austria
State/province [23] 0 0
Graz
Country [24] 0 0
Austria
State/province [24] 0 0
Wien
Country [25] 0 0
Belgium
State/province [25] 0 0
Bruxelles
Country [26] 0 0
Canada
State/province [26] 0 0
Alberta
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Germany
State/province [29] 0 0
BY
Country [30] 0 0
Germany
State/province [30] 0 0
HE
Country [31] 0 0
Israel
State/province [31] 0 0
Petach Tikva
Country [32] 0 0
Israel
State/province [32] 0 0
Ramat Gan
Country [33] 0 0
Mexico
State/province [33] 0 0
NL
Country [34] 0 0
Mexico
State/province [34] 0 0
Mexico City
Country [35] 0 0
Spain
State/province [35] 0 0
Barcelona
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Gt Lon

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT00832507
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gennyne Walker, PhD
Address 0 0
Senior Clinical Research Scientist, Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00832507