Back to resultsSafety and Efficacy of APD811 in Pulmonary Arterial Hypertension
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
APD811
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility Criteria
Inclusion Criteria:
- Males or females aged 18-75 years, inclusive
Symptomatic WHO Group 1 PAH classified by one of the following subgroups:
- Idiopathic pulmonary arterial hypertension (IPAH);
- Heritable pulmonary arterial hypertension (HPAH);
- Drugs and toxins induced;
- Associated pulmonary arterial hypertension (APAH); specifically connective tissue diseases, HIV infection and congenital heart disease.
- Has had the diagnosis of PAH confirmed by cardiac catheterization
- Has WHO/NYHA functional class II- IV symptomatology
- Previously diagnosed with PAH and on stable oral disease-specific PAH therapy with either an ERA and/or an agent acting on the nitric oxide pathway, i.e. a PDE5 inhibitor or a soluble guanylate cyclase stimulator. Stable is defined as no change in dose within 3 months of the start of Screening and for the duration of the study
- Has 6MWT distances of 100-500 m, and within 15% of each other on 2 consecutive tests done on different days at Screening
- Has pulmonary function tests (PFTs) within 6 months prior to the start of Screening with no evidence of significant parenchymal lung disease
- Has a ventilation-perfusion (V/Q) lung scan or pulmonary angiogram within 5 years prior to Screening and concomitant with or following diagnosis of PAH that shows no evidence of thromboembolic disease
- If on vasodilators (including calcium channel blockers), digoxin, spironolactone, or L-Arginine supplementation; the patient must be on a stable dose for at least 1 month prior to the start of Screening
Exclusion Criteria:
- Newly diagnosed with PAH and on no disease-specific PAH therapy
- Previous participation in any clinical study with an investigational drug, biologic, or device within 2 months prior to the Screening visit
- Acutely decompensated heart failure within 1 month prior to start of Screening
- Systolic blood pressure <90 mm Hg at Screening
- Evidence or history of left-sided heart disease and/or clinically significant cardiac disease
- Use or chronic administration (defined as >30 days) of a prostacyclin or prostacyclin analogue within 3 months of Screening
- Any previous use of a prostacyclin or prostacyclin analogue that was stopped for safety or tolerability issues associated with pharmacology/mechanism of action
- Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Sites / Locations
- University of Alabama at Birmingham
- Cedars-Sinai Medical Center
- UC Davis Medical Center
- UCLA Medical Center
- University of Iowa Hospitals and Clinics
- University of Maryland
- Boston University Medical Center
- University of Cincinnati
- Ohio State University Medical Center
- University of Pittsburg Medical Center
- UT Southwestern
- University of Texas, Houston Center for Clinical and Translational Sciences
- The Prince Charles Hospital
- St Vincent's Hospital
- St Vincent's Hospital
- Royal Hobart Hospital
- Fiona Stanley Hospital
- "Многопрофилната болница за активно лечение "Национална кардиологична болница "" ЕАД
- Многопрофилна болница за активно лечение "Света Анна" София АД, Клиника по кардиология
- II. interní klinika - klinika kardiologie a angiologie, 1. lékařská fakulta, Univerzita Karlova v Praze a Všeobecná fakultní nemocnice v Praze
- Gottsegen György Országos Kardiologiai Intézet, Felnőtt Kardiológia
- Semmelweis Egyetem Pulmonológiai Klinika
- Pécsi Tudományegyetem Klinikai Központ, Szívgyógyászati Klinika
- Uniwersytecki Szpital Kliniczny w Białymstoku
- Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie
- Wojewódzki Szpital Specjalistyczny im. W. Biegańskiego w Łodzi
- Institutul de Urgență pentru Boli Cardiovasculare, Secția Clinică Cardiologie III
- Institutul de Pneumoftiziologie "Marius Nasta", Secția Clinică Pneumoftiziologie IV
- Spitalul Clinic de Boli Infectioase si Pneumoftiziologie, Sectia Clinica Pneumologie II
- Klinički Centar Srbije (KCS), Klinika za kardiologiju
- Kliničko-bolnički centar (KBC) Zemun,Klinika za internu medicinu,Sluzba kardiologije
- Institut za plućne bolesti Vojvodine Sremska Kamenica (IPBVSK),
- Hospital Universitari General Vall d'Hebron, Servicio de Neumología
- Hospital Clinic de Barcelona, Departamento de Pneumologia
- Hospital 12 de Octubre, Departamento de Cardiologia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
APD811
Placebo
Arm Description
Multiple dose titration to maximum tolerated dose.
Multiple dose titration to maximum tolerated dose.
Outcomes
Primary Outcome Measures
Change From Baseline in Pulmonary Vascular Resistance (PVR)
Measurements of PVR from right heart catheterization were obtained prior to Day 1 of the dose titration period and at the end of the maintenance period (Week 22), approximately 4 hours after the last dose of study drug.
Change From Baseline in 6-minute Walk Distance (6MWD) in Patients With PAH
The 6MWT was conducted according to the modified guidelines issued by the American Thoracic Society prior to Day 1 of the dose titration period and at the end of the maintenance period (Week 22).
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02279160
Brief Title
Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension
Official Title
A Randomized, Double-blind, Parallel-group, Placebo-controlled Phase 2 Trial of Ralinepag, an Oral IP Receptor Agonist, in Patients With Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study was conducted as a placebo-controlled, randomized, 22-week double-blind study which included a dose titration period. An additional transition period occurred for those patients who elected to enroll into the open-label extension study, APD811-007. A total of 61 patients with PAH were enrolled.
Detailed Description
Study APD811-003 was a 22-week, randomized, double-blind, parallel-group, placebo-controlled study in subjects with symptomatic WHO Group 1 PAH. The study consisted of a dose titration period of up to 9 weeks, a 13-week maintenance period, and a follow-up visit that was to occur approximately 3 weeks after the end of the maintenance period (Week 25). The transition period of 3 weeks (±1 week) was to occur for those subjects who elected to enroll into the open-label extension (OLE) Study APD811-007.
Approximately 60 subjects with PAH were planned to be enrolled (61 actual). After screening, eligible subjects were randomized 2:1 to ralinepag (APD811) or to placebo. Randomization was stratified by baseline WHO/NYHA functional class (II versus III or IV). Subjects randomized to active therapy were given ralinepag at a starting dose of 0.01 mg BID. Subjects randomized to the placebo arm received matching placebo capsules to preserve the blind. Subjects were instructed to take the study drug (ralinepag or placebo) with food. Dosage was then uptitrated, as tolerated, over the course of the 9-week dose-titration period to a maximum dose of 0.3 mg BID. Although doses could be reduced based on tolerability, the final dosage reached was required to be stable during the 13-week treatment period prior to evaluation at Week 22.
Subjects could receive concomitant oral disease-specific PAH therapy consisting of an ERA and/or an agent acting on the nitric oxide pathway, a PDE-5 inhibitor or a sGC stimulator, provided the dose had remained stable for at least 3 months prior to the start of screening. It was recommended that subjects continue the same dose and regimen of these medications for the duration of the study. With the exception of prostanoids, the use of other supporting therapies, which may affect PAH, was also permitted.
During the study, assessments of efficacy were performed including PVR and other hemodynamic parameters as determined by RHC, the 6MWT, assessment of clinical worsening, BNP and NT-proBNP levels, WHO/NYHA functional class assessment of PAH. Safety assessments included standard evaluations of AEs, clinical laboratory values, vital signs, and ECG measurements.
At the end of the maintenance period, subjects who did not choose to participate in the OLE study were to discontinue study drug (ralinepag or placebo). All subjects that chose to continue in the OLE study were to remain on study drug until the follow-up visit at Week 25. This visit served as the baseline visit for the OLE study if the subject was eligible and chose to participate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
APD811
Arm Type
Experimental
Arm Description
Multiple dose titration to maximum tolerated dose.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Multiple dose titration to maximum tolerated dose.
Intervention Type
Drug
Intervention Name(s)
APD811
Other Intervention Name(s)
Ralinepag
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Change From Baseline in Pulmonary Vascular Resistance (PVR)
Description
Measurements of PVR from right heart catheterization were obtained prior to Day 1 of the dose titration period and at the end of the maintenance period (Week 22), approximately 4 hours after the last dose of study drug.
Time Frame
Baseline and 22 Weeks
Title
Change From Baseline in 6-minute Walk Distance (6MWD) in Patients With PAH
Description
The 6MWT was conducted according to the modified guidelines issued by the American Thoracic Society prior to Day 1 of the dose titration period and at the end of the maintenance period (Week 22).
Time Frame
Baseline and 22 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females aged 18-75 years, inclusive
Symptomatic WHO Group 1 PAH classified by one of the following subgroups:
Idiopathic pulmonary arterial hypertension (IPAH);
Heritable pulmonary arterial hypertension (HPAH);
Drugs and toxins induced;
Associated pulmonary arterial hypertension (APAH); specifically connective tissue diseases, HIV infection and congenital heart disease.
Has had the diagnosis of PAH confirmed by cardiac catheterization
Has WHO/NYHA functional class II- IV symptomatology
Previously diagnosed with PAH and on stable oral disease-specific PAH therapy with either an ERA and/or an agent acting on the nitric oxide pathway, i.e. a PDE5 inhibitor or a soluble guanylate cyclase stimulator. Stable is defined as no change in dose within 3 months of the start of Screening and for the duration of the study
Has 6MWT distances of 100-500 m, and within 15% of each other on 2 consecutive tests done on different days at Screening
Has pulmonary function tests (PFTs) within 6 months prior to the start of Screening with no evidence of significant parenchymal lung disease
Has a ventilation-perfusion (V/Q) lung scan or pulmonary angiogram within 5 years prior to Screening and concomitant with or following diagnosis of PAH that shows no evidence of thromboembolic disease
If on vasodilators (including calcium channel blockers), digoxin, spironolactone, or L-Arginine supplementation; the patient must be on a stable dose for at least 1 month prior to the start of Screening
Exclusion Criteria:
Newly diagnosed with PAH and on no disease-specific PAH therapy
Previous participation in any clinical study with an investigational drug, biologic, or device within 2 months prior to the Screening visit
Acutely decompensated heart failure within 1 month prior to start of Screening
Systolic blood pressure <90 mm Hg at Screening
Evidence or history of left-sided heart disease and/or clinically significant cardiac disease
Use or chronic administration (defined as >30 days) of a prostacyclin or prostacyclin analogue within 3 months of Screening
Any previous use of a prostacyclin or prostacyclin analogue that was stopped for safety or tolerability issues associated with pharmacology/mechanism of action
Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Derek Solum, PhD
Organizational Affiliation
United Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
University of Pittsburg Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15229
Country
United States
Facility Name
UT Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas, Houston Center for Clinical and Translational Sciences
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Prince Charles Hospital
City
Chermside
ZIP/Postal Code
4032
Country
Australia
Facility Name
St Vincent's Hospital
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
Facility Name
St Vincent's Hospital
City
Fitzroy
ZIP/Postal Code
3065
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
ZIP/Postal Code
7000
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
ZIP/Postal Code
6150
Country
Australia
Facility Name
"Многопрофилната болница за активно лечение "Национална кардиологична болница "" ЕАД
City
Sofia
ZIP/Postal Code
1309
Country
Bulgaria
Facility Name
Многопрофилна болница за активно лечение "Света Анна" София АД, Клиника по кардиология
City
Sofia
ZIP/Postal Code
1750
Country
Bulgaria
Facility Name
II. interní klinika - klinika kardiologie a angiologie, 1. lékařská fakulta, Univerzita Karlova v Praze a Všeobecná fakultní nemocnice v Praze
City
Prague
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Gottsegen György Országos Kardiologiai Intézet, Felnőtt Kardiológia
City
Budapest
ZIP/Postal Code
1096
Country
Hungary
Facility Name
Semmelweis Egyetem Pulmonológiai Klinika
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
Pécsi Tudományegyetem Klinikai Központ, Szívgyógyászati Klinika
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
Uniwersytecki Szpital Kliniczny w Białymstoku
City
Bialystok
ZIP/Postal Code
15-276
Country
Poland
Facility Name
Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie
City
Krakow
ZIP/Postal Code
31-202
Country
Poland
Facility Name
Wojewódzki Szpital Specjalistyczny im. W. Biegańskiego w Łodzi
City
Lodz
ZIP/Postal Code
91-347
Country
Poland
Facility Name
Institutul de Urgență pentru Boli Cardiovasculare, Secția Clinică Cardiologie III
City
Bucharest
ZIP/Postal Code
022322
Country
Romania
Facility Name
Institutul de Pneumoftiziologie "Marius Nasta", Secția Clinică Pneumoftiziologie IV
City
Bucharest
ZIP/Postal Code
050159
Country
Romania
Facility Name
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie, Sectia Clinica Pneumologie II
City
Timisoara
ZIP/Postal Code
300310
Country
Romania
Facility Name
Klinički Centar Srbije (KCS), Klinika za kardiologiju
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Kliničko-bolnički centar (KBC) Zemun,Klinika za internu medicinu,Sluzba kardiologije
City
Belgrade
ZIP/Postal Code
11080
Country
Serbia
Facility Name
Institut za plućne bolesti Vojvodine Sremska Kamenica (IPBVSK),
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
Facility Name
Hospital Universitari General Vall d'Hebron, Servicio de Neumología
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona, Departamento de Pneumologia
City
Barcelona
ZIP/Postal Code
11000
Country
Spain
Facility Name
Hospital 12 de Octubre, Departamento de Cardiologia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
31391223
Citation
Torres F, Farber H, Ristic A, McLaughlin V, Adams J, Zhang J, Klassen P, Shanahan W, Grundy J, Hoffmann I, Cabell C, Escribano Subias P, Sood N, Keogh A, D'Souza G, Rubin L. Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial. Eur Respir J. 2019 Oct 10;54(4):1901030. doi: 10.1183/13993003.01030-2019. Print 2019 Oct.
Results Reference
derived
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Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension
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