A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients

• Sponsor: United Therapeutics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03626688
• Collaborator: (none)
• Enrollment: 700
• Locations: 194
• Arms: 2
• Anticipated Duration (Months): 51.1
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.

Condition or Disease	Intervention/Treatment	Phase
PAH; Pulmonary Hypertension; Pulmonary Arterial Hypertension; Hypertension; Connective Tissue Diseases; Familial Primary Pulmonary Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Disease	Drug: Ralinepag; Drug: Placebo	Phase 3

Detailed Description

Study ROR-PH-301 is a multicenter, randomized, double-blind, placebo-controlled study. Subjects who meet entry criteria will be randomly allocated 1:1 to receive ralinepag or placebo, in addition to their standard of care or PAH-specific background therapy, as applicable. The primary endpoint is the time (in days) from randomization to the first adjudicated protocol-defined clinical worsening event. All primary endpoint events will be adjudicated by an independent Clinical Event Committee (CEC) in a blinded fashion. Subjects who have a confirmed primary endpoint event adjudicated by the CEC at any time during the study and all subjects on treatment at the conclusion of the study (after the target number of events is achieved) will have the option to enroll in an open-label extension (OLE) study. Subjects who do not choose to participate in the OLE study will discontinue study drug, and should remain in the study for long-term follow-up of survival status and will receive standard of care PAH treatment, at the discretion of the treating physician.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 700 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ralinepag When Added to PAH Standard of Care or PAH Specific Background Therapy in Subjects With WHO Group 1 PAH
• Actual Study Start Date: Aug 30, 2018
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ralinepag Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the highest tolerated dose.	Drug: Ralinepag; Active; Other Names: APD811
Placebo Comparator: Placebo Matching placebo tablets (oral)	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Time from randomization to the first adjudicated protocol-defined clinical worsening event [The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study, up to 3 years]

   Clinical worsening events are defined as death, nonelective hospital admission for worsening PAH (further defined in clinical study protocol), initiation of parenteral or inhaled prostacyclin pathway agent for treatment of worsening PAH, disease progression (further defined in clinical study protocol), or unsatisfactory long-term clinical response (further defined in clinical study protocol).

Secondary Outcome Measures

1. Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) [Baseline to Week 28]

   NT-proBNP was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

2. Change from Baseline in 6-minute walk distance (6MWD) [Baseline to Week 28]

   6MWD was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

3. Change from Baseline in WHO/New York Heart Association (NYHA) Functional Class [Baseline to Week 28]

   The severity of PAH was graded according to the functional status of the subject and assessed at every visit.

4. Shift and proportion of subjects who attain all 3 of the following: NT-proBNP level <300 pg/mL, 6MWD >440 meters, and WHO/NYHA Functional Class I or II [Baseline to Week 28]

   Data from NT-proBNP, 6MWD, and WHO/NYHA functional class assessment were compiled as a composite endpoint at visits through Week 28.

5. Change from Baseline in health-related quality of life as measured by patient-reported outcomes. [Baseline to Week 28]

   Quality of life was assessed using patient-reported outcomes at Baseline (prior to starting study drug) and Week 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

6. Time to first all-cause nonelective hospitalization [The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).]

   All nonelective hopsitalizations during the study period were collected.

7. Time to all-cause mortality [The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).]

   All deaths during the study period were collected.

8. Change from Baseline in heart rate recovery (HRR) following completion of the 6MWT [Baseline to Week 28]

   HRR was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.

9. Safety and tolerability of ralinepag in subjects with PAH [Baseline to Week 28]

   Safety and tolerability were assessed by adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. At least 18 years of age.

2. Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.

3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

4. Primary diagnosis of symptomatic PAH.

5. Has had a right heart catheterization (RHC) performed at or within 3 years prior to Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH.

6. Has WHO/ NYHA functional class II to IV symptoms.

7. If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator. Subjects may be naïve to PAH-specific treatment.

8. Has a 6MWD of ≥150 meters.

9. If taking concomitant medications that may affect the clinical manifestations of PAH (eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics must be stable for at least the 10 days prior to Baseline.

10. Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through to the 30-Day Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process during the study and for 30 days after the last dose of IMP. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of IMP.

Exclusion Criteria:

1. For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Baseline.

2. Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.

3. Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.

4. Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.

5. Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.

6. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and female subjects with a QTcF >470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is >500 msec for both males and females.

7. Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).

8. Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).

9. Subjects with alanine aminotransferase or aspartate aminotransferase ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.

10. Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL or requiring dialysis at Screening.

11. Hemoglobin concentration <9 g/dL at Screening.

12. Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).

13. Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) within 90 days prior to Baseline.

14. Subject has pulmonary veno-occlusive disease.

15. Malignancy diagnosed and/or treated within 5 years prior to Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.

16. Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse. A subject will not be excluded due to a positive drug screen caused by prescribed medications.

17. Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.

18. Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.

19. Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study (eg, any previous or intercurrent medical condition) that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation.

20. Known hypersensitivity to ralinepag or any of the excipients.

21. Life expectancy <12 months based on the Investigator's opinion.

22. Women who are pregnant, lactating or breast-feeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259
3	University of Arizona	Tucson	Arizona	United States	85724
4	UCSD Health Sciences	La Jolla	California	United States	92037
5	Loma Linda University Medical Center	Loma Linda	California	United States	92354
6	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90024
7	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
8	Keck Hospital of USC	Los Angeles	California	United States	90033
9	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
10	VA Greater Los Angeles Healthcare System	Los Angeles	California	United States	90073
11	University of California Davis Medical Center	Sacramento	California	United States	95817
12	Santa Barbara Cottage Hospital	Santa Barbara	California	United States	93105
13	Stanford University Medical Center	Stanford	California	United States	94305
14	University of Colorado Hospital	Aurora	Colorado	United States	80045
15	National Jewish Health	Denver	Colorado	United States	80206
16	University of Florida	Gainesville	Florida	United States	32610
17	Mayo Clinic Florida	Jacksonville	Florida	United States	32224
18	University of Miami	Miami	Florida	United States	33136
19	Central Florida Pulmonary Group	Orlando	Florida	United States	32803
20	Cleveland Clinic Florida	Weston	Florida	United States	33331
21	Emory University Hospital	Atlanta	Georgia	United States	30322
22	Piedmont Healthcare Pulmonary and Critical Care Research	Austell	Georgia	United States	30106
23	University of Chicago Medical Center	Chicago	Illinois	United States	60637
24	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
25	St. Vincent Medical Group, Inc.	Indianapolis	Indiana	United States	46260
26	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
27	Kentuckiana Pulmonary Research Center	Louisville	Kentucky	United States	40202
28	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
29	Chest Medicine Associates	South Portland	Maine	United States	04106
30	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
31	Tufts Medical Center	Boston	Massachusetts	United States	02111
32	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
33	Boston University Medical Center	Boston	Massachusetts	United States	02118
34	Spectrum Health Medical Group	Grand Rapids	Michigan	United States	49546
35	Mayo Clinic	Rochester	Minnesota	United States	55905
36	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
37	Nebraska Medical Center	Omaha	Nebraska	United States	68198
38	University of New Mexico	Albuquerque	New Mexico	United States	87131
39	Winthrop Hospital	Mineola	New York	United States	11501
40	NYU Langone Medical Center	New York	New York	United States	10016
41	Weill-Cornell-New York Presbyterian Hospital	New York	New York	United States	10021
42	Mount Sinai School of Medicine	New York	New York	United States	10029
43	University of Rochester	Rochester	New York	United States	14642
44	Duke University Medical Center	Durham	North Carolina	United States	27710
45	East Carolina University	Greenville	North Carolina	United States	27834
46	University of Cincinnati-Medical Science Building	Cincinnati	Ohio	United States	45267
47	Cleveland Clinic	Cleveland	Ohio	United States	44195
48	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
49	Integris Baptist Medical Center	Oklahoma City	Oklahoma	United States	73112
50	Oregon Clinic-Pulmonary West	Portland	Oregon	United States	97225
51	Oregon Health & Science University	Portland	Oregon	United States	97239
52	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
53	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
54	Temple University	Philadelphia	Pennsylvania	United States	19140
55	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
56	NewSTAT, PLLC	Knoxville	Tennessee	United States	37919
57	UT Southwestern Medical Center	Dallas	Texas	United States	75390
58	Memorial Hermann Hospital	Houston	Texas	United States	77030
59	The Methodist Hospital Research Institute	Houston	Texas	United States	77030
60	Vermont Lung Center	Burlington	Vermont	United States	05446
61	University of Virginia Medical Center	Charlottesville	Virginia	United States	22908
62	Sentara Cardiovascular Research Institute	Norfolk	Virginia	United States	23507
63	Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin	United States	53226
64	Hospital Italiano	Ciudad Autonoma Buenos Aires	Buenos Aires	Argentina	C1181ACH
65	Sanatorio Parque S.A.	Rosario	Santa Fe	Argentina	S2000DSV
66	Sanatorio de la Trinidad Mitre	Buenos Aires		Argentina
67	Cardiologia Palmero	Caba		Argentina	1425
68	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires		Argentina	1280
69	Fundacion Respirar	Ciudad Autonoma Buenos Aires		Argentina	1426
70	Fundacion Favaloro	Ciudad Autonoma Buenos Aires		Argentina	C1093AAS
71	Hospital Italiano de Cordoba	Cordoba		Argentina	X5004BAL
72	Hospital Privado Centro Medico de Cordoba S.A	Cordoba		Argentina	X5016KEH
73	Instituto de Cardiologia de Corrientes	Corrientes		Argentina
74	Instituto de Investigaciones Clinicas	Mar Del Plata		Argentina
75	Hospital PROVINCIAL "Dr. Jose Maria Cullen"	Sante Fe		Argentina	3000
76	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
77	Royal Prince Alfred Hospital	Sydney	New South Wales	Australia	2050
78	Macquarie University	Sydney	New South Wales	Australia	2109
79	Westmead Hospital	Sydney	New South Wales	Australia	2145
80	Nepean Hospital	Sydney	New South Wales	Australia	2751
81	The Prince Charles Hospital	Chermside	Queensland	Australia	4032
82	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
83	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
84	St Vincent's Hospital Melbourne	Fitzroy	Victoria	Australia	3065
85	The Alfred Hospital	Melbourne	Victoria	Australia	3004
86	Fiona Stanley Hospital	Perth	Western Australia	Australia	6150
87	Medizinische Universität Innsbruck	Innsbruck		Austria	6020
88	Ordensklinikum Linz GmbH - Elisabethinen, Fadingerstrasse 1	Linz		Austria	4020
89	AKH Wien, Innere Med. II, Kardiologie, Währingergürtel 18-20	Wien		Austria	1090
90	Cliniques Universitaires de Bruxelles Hopital Erasme	Bruxelles		Belgium	1070
91	UZ Leuven, UZ Leuven Campus Gasthuisberg, Herestraat 49	Leuven		Belgium	3000
92	HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás	Goiânia	Goias	Brazil	74605-020
93	Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa	Belo Horizonte	MG	Brazil	30441-070
94	Hospital Sao Lucas da PUC-RS	Porto Alegre	R.S	Brazil	90610-000
95	Irmandade da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre	RS	Brazil	90035-074
96	UNESP-Faculdade de Medicina da Universidade Estadual Paulista Campus Botucatu	Botucatu	Sao Paulo	Brazil	18618-687
97	Hospital Sao Paulo	Sao Paulo	SP	Brazil	04037-002
98	Instituto do Coracao	Sao Paulo	SP	Brazil	05403-000
99	MHAT - "National Heart Hospital" EAD, 65, Konyovitza Str.	Sofia		Bulgaria	1309
100	MHAT "Sveta Anna" Sofia AD	Sofia		Bulgaria	1750
101	Peter Lougheed Centre	Calgary	Alberta	Canada	T1Y 6J4
102	LHSC - Victoria Hospital	London	Ontario	Canada	N6A 5W9
103	University Health Network-Toronto General Hospital	Toronto	Ontario	Canada	M5G 2N2
104	SMBD Jewish General Hospital d/b/a Jewish General Hospital	Montreal	Quebec	Canada	H3T1E2
105	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Québec	Quebec	Canada
106	Instiuto Nacional del Torax	Providencia	Santiago De Chile	Chile	7500691
107	Beijing Shijitan Hospital, Capital Medical University	Beijing	Beijing	China	100038
108	Guangdong Provincial People's Hospital	Guangzhou	Guangdong	China	510080
109	Xiangya Hospital Central South University	Changsha	Hunan	China	410008
110	Shanghai Pulmonary Hospital	Shanghai	Shanghai	China	200443
111	Fuwai Hospital, Chinese Academy of Medical Sciences	Beijing		China	100037
112	Clinical Hospital Dubrava Zagreb, Avenija G.Šuška 6	Zagreb		Croatia	10000
113	University Clinic for Pulmonary Diseases, Jordanovac 104	Zagreb		Croatia	10000
114	Vseobecna fakultni nemocnice v Praze, II. interni klinika kardiologie a angiologie VFN a 1. LF UK, U nemocnice 2	Praha 2		Czechia	128 08
115	Copenhagen University Hospital (Rigshospitalet)	Copenhagen		Denmark	2100
116	Århus Universitetshospital	Århus		Denmark	8200
117	CHU de Strasbourg - Nouvel Hôpital Civil, Ctre de competence Hypertension Arterielle Pulmona, 1 place de l Hopital	Strasbourg	Bas Rhin	France	67091
118	CHU de Grenoble - Hôpital Albert Michallon, Clinique de Cardiologie, Boulevrad de la Chantourne	Grenoble	Isere	France	38048
119	CHU de Saint-Etienne - Hopital Nord, Service de Medecine vasculaire et therapeutique, 81 Avenue A. Raimond	Saint-Étienne	Loire	France	42005
120	CHU Nancy - Hôpital de Brabois Adultes, Pneumologie- Oncologie Médicale, Rue du Morvan	Vandoeuvre les Nancy	Meurthe Et Moselle	France	54511
121	CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel, Service de Pneumologie, 59 Boulevard Pinel	Bron cedex	Rhone	France	69677
122	CHU de Rouen - Hôpital Charles Nicolle	Rouen cedex	Seine Maritime	France	76031
123	Groupement Hospitalier Sud - Hôpital Bicêtre	Le Kremlin-Bicêtre	Val De Marne	France	94275
124	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex		France	25030
125	CHU de Brest - Hôpital de la Cavale Blanche	Brest cedex 2		France	29609
126	CHRU de Lille - Hopital Cardiologique	Lille Cedex		France	59037
127	Hôpital Nord - CHU Marseille	Marseille		France	13015
128	Thoraxklinik-Heidelberg Zentrum für Pulmonale Hypertonie	Heidelberg	Baden-Württemberg	Germany	69126
129	Universitätsmedizin Greifswald	Greifswald	Mecklenburg-Vorpommern	Germany	17475
130	Universitaetsmedizin der Johannes-Gutenberg-Universitaet Mainz, Zentrum für Kardiologie I, Centrum für Thrombose und Hämostase (CTH), Langenbeckstrasse 1	Mainz	Rheinland Pfalz	Germany	55131
131	Universitaetsklinikum des Saarlandes, Innere Medizin V, IMED, Kirrberger Strasse 100, Gebäude 41	Homburg	Saarland	Germany	66424
132	Universitätsklinikum Leipzig, Medizinische Klinik II, Pneumologie	Leipzig	Sachsen	Germany	04103
133	Schwarzwald-Baar Klinikum	Donaueschingen		Germany	78166
134	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden		Germany	01307
135	Universitaetsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
136	University General Hospital of Alexandroupolis	Alexandroupolis		Greece	68100
137	"Onasseio" Cardiosurgery Hospital, Hemodynamic Research and Interventional Cardiology Dept., 356, Syggrou Avenue	Athens		Greece	17674
138	University General Hospital Attikon	Chaidari		Greece	12462
139	AHEPA General Hospital of Thessaloniki, A' Cardiology Clinic, 1 St. Kyriakidi Street	Thessaloniki		Greece	54636
140	Pecsi Tudomanyegyetem, Szivgyogyaszati Klinika, Ifjusag u. 13.	Pecs		Hungary	7624
141	The Lady Davis Carmel Medical Center, 7 Michal st.	Haifa		Israel	3436212
142	Hadassah Ein Kerem Medical Center, Kiryat Hadassah	Jerusalem		Israel	9112001
143	Meir Medical Center, 59 Tshernichovski st.	Kfar- Sava		Israel	4428164
144	Rabin Medical Center-Beilinson Campus, Pulmonary Institute, 39 Jabotinsky St Ground floor	Petach Tikva		Israel	4941492
145	Tel Aviv Sourasky Medical Center, 6 Weizmann St.	Tel Aviv		Israel	6423906
146	Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia, S.C. di Cardiologia, Viale Luigi Pinto, 1	Foggia		Italy	71100
147	IRCC Ospedale Policlinico San Martino	Genova		Italy	16132
148	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35	Milano		Italy	20122
149	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)	Monza		Italy	20900
150	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
151	Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza, Viale del Policlinico, 155	Roma		Italy	00161
152	Samsung Medical Center	Seoul	Gangnam-gu	Korea, Republic of	06351
153	Seoul National University Hospital	Seoul	Jongno-gu	Korea, Republic of	03080
154	Gachon University Hospital Gil Medical Center	Incheon	Namdong-gu	Korea, Republic of	21565
155	Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera	Mexico	Distrito Federal	Mexico	14080
156	Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran	Mexico	Distrito Federal	Mexico	14080
157	CICUM San Miguel	Guadalajara	Jalisco	Mexico	44160
158	Unidad de Investigacion Clinica en Medicina, S.C.	Monterrey	N.l.	Mexico	64718
159	VU Medisch Centrum, De Boelelaan 1117	Amsterdam		Netherlands	1081 HV
160	Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Kardiologii z Oddzialem Intensywnego Nazdoru Kardiologicznego, M. Sklodowskiej 24a	Bialystok		Poland	15-276
161	Krakowski Szpital Specjalistyczny im. Jana Pawla II, Oddział Kliniczny Chorób Serca i Naczyń z Pododdziałem Intensywnego Nadzoru Kardiologicznego, Pradnicka 80	Krakow		Poland	31-202
162	NZOZ Europejskie Centrum Zdrowia, ul. Borowa 14/18	Otwock		Poland	05-400
163	Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu, Oddzial Kardiologii - F, ul. Dluga 1/2	Poznan		Poland	61-848
164	Premium Clinic Wrocław CM, Podwale 83/17	Wroclaw		Poland	50-414
165	Hospital Garcia de Orta, E.P.E	Almada		Portugal	2805-267
166	Centro Hospitalar e Universitário de Coimbra, E.P.E.	Coimbra		Portugal	3000-075
167	Centro Hospitalar Universitário Lisboa Norte, E.P.E. Hospital Pulido Valente	Lisboa		Portugal	1769-001
168	Institutul de Urgenta pentru Boli Cardiovasculare "Prof. Dr. C.C. Iliescu", Sos. Fundeni nr. 258	Bucharest		Romania	022328
169	Institutul de Pneumoftiziologie "Marius Nasta", Sos. Viilor nr. 90, Sector 5	Bucuresti		Romania	050159
170	Institutul Inimii "Niculae Stancioiu" Cluj-Napoca, Cardiologie, Str. Motilor nr. 19-21	Cluj-Napoca		Romania	400001
171	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes" Timisoara, Str. Gheorghe Adam nr. 13	Timisoara		Romania	300310
172	Clinical Center of Serbia, Koste Todorovica 8	Belgrade		Serbia	11000
173	Clinical Center Zemun. Clinic for internal medicine, Department of Cardiology	Belgrade		Serbia	11080
174	Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana 4	Sremska Kamenica		Serbia	21204
175	National University Hospital	Singapore		Singapore	119074
176	National Heart Centre	Singapore		Singapore	169609
177	Hospital Universitari Vall d'Hebron, Respiratory Dept., Passeig Vall d'Hebron,119-129, Neumologia	Barcelona		Spain	08035
178	Hospital Clinic de Barcelona, C/ Villarroel, 170	Barcelona		Spain	08036
179	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
180	Sahlgrenska Universitetssjukhuset	Göteborg		Sweden	41345
181	Linköping Universitetssjukhuset	Linköping		Sweden	58185
182	Norrlands Universitetssjukhus, Hjärtcentrum	Umeå		Sweden	90185
183	National Cheng Kung University Hospital	Tainan		Taiwan	704
184	National Taiwan University Hospital	Taipei		Taiwan	10002
185	Uludag Universitesi Tip Fakültesi, Gorukle Kampusu	Bursa		Turkey	16059
186	Marmara Universitesi Istanbul Pendik Egitim ve Arastirma Hastanesi, Fevzi Cakmak Mahallesi Muhsin Yazicioglu Cad. No: 10	Istanbul		Turkey	34899
187	Dokuz Eylul Universitesi Tip Fakultesi, Mithatpasa caddesi Inciralti Balcova	Izmir		Turkey	35340
188	CE Dniprop RCC&C Center of Dniprop RC Dept of Card SI DMA of MOHU, Chair of Internal Medicine 3, 28, Knyazya Volodymyra Velykogo St.	Dnipro		Ukraine	49070
189	SI F.H.Yanovskyi National Institute of Phthisiology and Pulmonology of NAMSU, Clinical and Functional Dept, 10, Amosova St.	Kyiv		Ukraine	03680
190	Communal Noncommercial Enterprise of Lviv Regional Council Lviv Clinical Hospital, Dept of Cardiology, D.Halytskyi Lviv NMU, Ch of Internal Medicine #1, 7, Chernihivska str.	Lviv		Ukraine	79010
191	Royal Free London NHS Foundation Trust, Pond Street	London	Greater London	United Kingdom	NW3 2QG
192	The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir William Leech Lung Research Centre, Freeman Hospital	Newcastle upon Tyne	Tyne & Wear	United Kingdom	NE7 7DN
193	Golden Jubilee National Hospital	Glasgow	West Dunbartonshire	United Kingdom	G81 4DY
194	Royal Brompton Hospital	London		United Kingdom	SW3 6NP

Sponsors and Collaborators

• United Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: United Therapeutics
• ClinicalTrials.gov Identifier: NCT03626688
• Other Study ID Numbers: ROR-PH-301; APD811-301
• First Posted: Aug 13, 2018
• Last Update Posted: Jun 10, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by United Therapeutics: Prostacyclin; Connective Tissue Disease-Associated; 6 Minute Walk Test; 6 Minute Walk Distance; Pulmonary Vascular Resistance; Right Ventricular Function
• Additional relevant MeSH terms: Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Respiratory Tract Diseases; Familial Primary Pulmonary Hypertension; Hypertension; Cardiovascular Diseases; Vascular Diseases; Connective Tissue Diseases

Study Results

No Results Posted as of Jun 10, 2022