The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01560624




Registration number
NCT01560624
Ethics application status
Date submitted
9/03/2012
Date registered
22/03/2012
Date last updated
13/02/2020

Titles & IDs
Public title
Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy
Scientific title
A Phase III, International, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Clinical Worsening Study of UT-15C in Subjects With Pulmonary Arterial Hypertension Receiving Background Oral Monotherapy
Secondary ID [1] 0 0
TDE-PH-310
Universal Trial Number (UTN)
Trial acronym
FREEDOM-EV
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 - Treprostinil Diolamine
Treatment: Drugs - Placebo

Experimental: UT-15C - Treprostinil diolamine extended-release tablets (oral) 0.125 to 12 mg TID

Placebo comparator: Placebo - Matching placebo tablets (oral)


Treatment: Drugs: Treprostinil Diolamine
Active

Treatment: Drugs: Placebo
Placebo

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to First Clinical Worsening Event
Timepoint [1] 0 0
From randomization to approximately 4 years
Secondary outcome [1] 0 0
Change in 6-Minute Walk Distance
Timepoint [1] 0 0
From Baseline to Week 24
Secondary outcome [2] 0 0
Change in Plasma N-Terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 24
Timepoint [2] 0 0
From Baseline to Week 24
Secondary outcome [3] 0 0
Change in World Health Organization Functional Class (WHO FC) From Baseline to Week 48
Timepoint [3] 0 0
Baseline to Week 48

Eligibility
Key inclusion criteria
Subject

1. Voluntarily gave informed consent to participate in the study.
2. Are 18 to 75 years of age (inclusive) at Screening.
3. Women of childbearing potential must practice abstinence from intercourse when in line with their preferred and usual lifestyle, or use 2 different forms of highly effective contraception for the duration of the study, and for at least 30 days after discontinuing study medication. A negative urine pregnancy test is required at Screening and Baseline prior to initiating study medication.
4. Male subjects must consent to use a condom during intercourse for the duration of the study, and for at least 48 hours after discontinuing study medication.
5. Have a diagnosis of symptomatic idiopathic or heritable PAH, PAH associated with connective tissue disease (CTD), PAH associated with HIV infection, PAH associated with repaired congenital systemic-to-pulmonary shunt, or PAH associated with appetite suppressant or toxin use.
6. If known to be positive for HIV infection, have a CD4 lymphocyte count of at least 200 cells/mm^3 assessed at Screening and are receiving current standard of care anti retroviral or other effective medication for the treatment of HIV infection.
7. Have a baseline 6MWD greater than or equal to 150 m in the absence of a concurrent injury, illness, or other confounding factor including, but not limited to, use of an aid for ambulation or connection to a nonportable machine, that would have prevented the accurate assessment of the subject's exercise capacity.
8. Are optimally treated with conventional pulmonary hypertension therapy with no additions, discontinuations, or dose changes for a minimum of 10 days prior to randomization. The exceptions are the discontinuation or dose changes of anticoagulants and/or dose change of diuretics.
9. Are receiving a PAH-approved oral monotherapy at a minimum dose that complies with the approved prescribing information for the product for at least 30 days prior to randomization and are receiving a stable dose for at least 10 days prior to randomization.
10. Have had previously undergone a cardiac catheterization within 3 years prior to the start of Screening or during the Screening Period, and the most recent assessment documented a pulmonary artery pressure mean of at least 25 mmHg, a pulmonary capillary wedge pressure (PCWP) (or in the event a PCWP could not be reliably obtained, a left ventricular end diastolic pressure [LVEDP]) less than or equal to 15 mmHg, and absence of unrepaired congenital heart disease (other than patent foramen ovale). If a reliable PCWP or LVEDP are unable to be obtained during cardiac catheterization, subjects with clinically normal left heart function and absence of clinically relevant mitral valve disease on echocardiography are eligible for enrollment.
11. Undergo echocardiography with evidence of clinically normal systolic and diastolic left ventricular function and absence of any clinically significant left sided heart disease (eg, mitral valve disease). Subjects with clinically insignificant left ventricular diastolic dysfunction due to the effects of right ventricular overload (ie, right ventricular hypertrophy and/or dilatation) are eligible.
12. Have a previous ventilation perfusion lung scan, high-resolution computerized tomography scan of the chest, and/or pulmonary angiography that are consistent with the diagnosis of PAH.
13. Have pulmonary function tests conducted within 6 months before Screening or during the Screening Period to confirm the following:

1. Total lung capacity is at least 60%
2. Forced expiratory volume at 1 second is at least 50%
14. In the opinion of the Principal Investigator, is able to communicate effectively with study personnel and is considered reliable, willing, and likely to cooperate with protocol requirements, including attending all study visits.

Subject
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Is pregnant or lactating.
2. Have previously received oral treprostinil.
3. Have received a PGI2 (except if used during acute vasoreactivity testing) within 30 days prior to randomization or have previous intolerance or significant lack of efficacy to any PGI2 or PGI2 analogue that resulted in discontinuation or inability to titrate that therapy effectively.
4. Have any background conventional therapies for PAH added, removed, or dose-adjusted within 10 days prior to randomization. The exceptions are removal or dose adjustments of anticoagulants and/or dose adjustments of diuretics.
5. Receive their first dose of a PAH-approved oral monotherapy less than 30 days prior to randomization, or have their PAH-approved oral monotherapy dose changed within 10 days prior to randomization, or the subject discontinues any PAH approved therapy within 30 days prior to Screening, or the subject has previously received 2 PAH approved oral therapies at the same time (specifically, a PDE5-I, an ERA, or a sGC stimulator) concomitantly for more than 90 days cumulatively.
6. Have any disease associated with PAH other than CTD, HIV infection, repaired (for at least 1 year) congenital systemic-to-pulmonary shunt, PAH associated with appetite suppressant/toxin use, or have an atrial septostomy.
7. Have a current diagnosis of uncontrolled sleep apnea as defined by their physician.
8. Have a history of ischemic heart disease, including a previous myocardial infarction or symptomatic coronary artery disease within 6 months prior to Screening or a history of left-sided myocardial disease as evidenced by a mean PCWP (or a LVEDP) greater than 15 mmHg or left ventricular ejection fraction less than 40% as assessed by either multigated angiogram, angiography, or echocardiography.
9. Have uncontrolled systemic hypertension as evidenced by systolic blood pressure (BP) greater than 160 mmHg or diastolic BP greater than 100 mmHg.
10. Have alanine aminotransferase or aspartate aminotransferase levels at least 3 times greater than the upper limit of normal, clinically significant liver disease/dysfunction, or known Child-Pugh Class C hepatic disease at Screening.
11. Have any other disease or condition that would interfere with the interpretation of study assessments.
12. Have a musculoskeletal disorder, is using a device to assist walking, or any disease that is likely to limit ambulation, or is connected to a machine that is nonportable.
13. Have an unstable psychiatric condition or is mentally incapable of understanding the objectives, nature, or consequences of the study, or has any condition which in the Investigator's opinion would constitute an unacceptable risk to the subject's safety.
14. Is receiving an investigational drug, have an investigational device in place, or have participated in an investigational drug or device study within 30 days prior to Screening.
15. Have chronic renal insufficiency as defined by either a Screening creatinine value greater than 2.5 mg/dL or the requirement for dialysis.
16. Does not have 3 or more of the following left ventricular disease/dysfunction risk factors:

1. Body mass index at least 30 kg/m^2
2. History of essential hypertension
3. Diabetes mellitus (any type)
4. Historical evidence of significant coronary artery disease established by any 1 of the following: history of myocardial infarction, percutaneous coronary intervention, or angiographic evidence of coronary artery disease; positive stress test with imaging; previous coronary artery bypass graft; or stable angina.

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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 0 0
Saint Vincents Hospital - Sydney
Recruitment hospital [4] 0 0
Macquarie University - Sydney
Recruitment hospital [5] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [6] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [7] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2751 - Kingswood
Recruitment postcode(s) [3] 0 0
2010 - Sydney
Recruitment postcode(s) [4] 0 0
2109 - Sydney
Recruitment postcode(s) [5] 0 0
4032 - Chermside
Recruitment postcode(s) [6] 0 0
7000 - Hobart
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
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
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
Rhode Island
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
Argentina
State/province [24] 0 0
Buenos Aires
Country [25] 0 0
Argentina
State/province [25] 0 0
Distrito Federal
Country [26] 0 0
Argentina
State/province [26] 0 0
Santa Fe
Country [27] 0 0
Austria
State/province [27] 0 0
Upper Austria
Country [28] 0 0
Austria
State/province [28] 0 0
Wien
Country [29] 0 0
Brazil
State/province [29] 0 0
Goias
Country [30] 0 0
Brazil
State/province [30] 0 0
Minas Gerais
Country [31] 0 0
Brazil
State/province [31] 0 0
RIO Grande DO SUL
Country [32] 0 0
Brazil
State/province [32] 0 0
SAO Paulo
Country [33] 0 0
Brazil
State/province [33] 0 0
São Paulo
Country [34] 0 0
Canada
State/province [34] 0 0
Alberta
Country [35] 0 0
Canada
State/province [35] 0 0
British Columbia
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Chile
State/province [37] 0 0
Region Metropolitana
Country [38] 0 0
Chile
State/province [38] 0 0
Santiago
Country [39] 0 0
China
State/province [39] 0 0
Beijing
Country [40] 0 0
China
State/province [40] 0 0
Guangdong
Country [41] 0 0
China
State/province [41] 0 0
Hubei
Country [42] 0 0
China
State/province [42] 0 0
Hunan
Country [43] 0 0
China
State/province [43] 0 0
Jiangsu
Country [44] 0 0
China
State/province [44] 0 0
Jiangxi
Country [45] 0 0
China
State/province [45] 0 0
Shanghai
Country [46] 0 0
China
State/province [46] 0 0
Sichuan
Country [47] 0 0
China
State/province [47] 0 0
Qingdao
Country [48] 0 0
China
State/province [48] 0 0
Shenyang
Country [49] 0 0
Denmark
State/province [49] 0 0
Aarhus
Country [50] 0 0
Denmark
State/province [50] 0 0
Copenhagen
Country [51] 0 0
France
State/province [51] 0 0
Aquitaine
Country [52] 0 0
France
State/province [52] 0 0
Franche-comte
Country [53] 0 0
France
State/province [53] 0 0
Languedoc-roussillon
Country [54] 0 0
France
State/province [54] 0 0
Limousin, Lorraine
Country [55] 0 0
France
State/province [55] 0 0
NORD Pas-de-calais
Country [56] 0 0
France
State/province [56] 0 0
Provence Alpes COTE D'azur
Country [57] 0 0
Germany
State/province [57] 0 0
Baden-wuerttemberg
Country [58] 0 0
Germany
State/province [58] 0 0
Bayern
Country [59] 0 0
Germany
State/province [59] 0 0
Mecklenburg-vorpommern
Country [60] 0 0
Germany
State/province [60] 0 0
Nordrhein-westfalen
Country [61] 0 0
Germany
State/province [61] 0 0
Rheinland-pfalz
Country [62] 0 0
Germany
State/province [62] 0 0
Saarland
Country [63] 0 0
Germany
State/province [63] 0 0
Sachsen
Country [64] 0 0
Germany
State/province [64] 0 0
Hamburg
Country [65] 0 0
Greece
State/province [65] 0 0
Attica
Country [66] 0 0
Greece
State/province [66] 0 0
Macedoni
Country [67] 0 0
India
State/province [67] 0 0
Andhra Pradesh
Country [68] 0 0
India
State/province [68] 0 0
Delhi
Country [69] 0 0
India
State/province [69] 0 0
Gujarat
Country [70] 0 0
India
State/province [70] 0 0
Haryana
Country [71] 0 0
India
State/province [71] 0 0
Karnataka
Country [72] 0 0
India
State/province [72] 0 0
Maharashtra
Country [73] 0 0
India
State/province [73] 0 0
Tamil NADU
Country [74] 0 0
Israel
State/province [74] 0 0
Petah Tiqwa
Country [75] 0 0
Israel
State/province [75] 0 0
Tel Aviv
Country [76] 0 0
Israel
State/province [76] 0 0
Haifa
Country [77] 0 0
Israel
State/province [77] 0 0
Jerusalem
Country [78] 0 0
Italy
State/province [78] 0 0
Napoli
Country [79] 0 0
Italy
State/province [79] 0 0
Palermo
Country [80] 0 0
Italy
State/province [80] 0 0
Pavia
Country [81] 0 0
Italy
State/province [81] 0 0
Roma
Country [82] 0 0
Korea, Republic of
State/province [82] 0 0
Incheon
Country [83] 0 0
Korea, Republic of
State/province [83] 0 0
Seoul
Country [84] 0 0
Mexico
State/province [84] 0 0
Distrito Federal
Country [85] 0 0
Mexico
State/province [85] 0 0
Nuevo LEON
Country [86] 0 0
Netherlands
State/province [86] 0 0
Gelderland
Country [87] 0 0
Netherlands
State/province [87] 0 0
Noord-holland
Country [88] 0 0
Poland
State/province [88] 0 0
Bialystok
Country [89] 0 0
Poland
State/province [89] 0 0
Krakow
Country [90] 0 0
Poland
State/province [90] 0 0
Malogoskie
Country [91] 0 0
Poland
State/province [91] 0 0
Otwock
Country [92] 0 0
Singapore
State/province [92] 0 0
Singapore
Country [93] 0 0
Sweden
State/province [93] 0 0
Vastra Gotaland
Country [94] 0 0
Sweden
State/province [94] 0 0
Stockholm
Country [95] 0 0
Taiwan
State/province [95] 0 0
Tainan CITY
Country [96] 0 0
Taiwan
State/province [96] 0 0
Kaohsiung
Country [97] 0 0
Taiwan
State/province [97] 0 0
Taichung
Country [98] 0 0
Taiwan
State/province [98] 0 0
Taipei
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Cambridgshire
Country [100] 0 0
United Kingdom
State/province [100] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
United Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James White, MD, PhD
Address 0 0
Mary M. Parkes Center
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.