Pulmonary Arterial HypertensionPhase 2NCT02279160
Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension
A Phase 2 study testing APD811 in people with Pulmonary Arterial Hypertension, run by United Therapeutics at 35 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- APD811
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 35 sitesin 9 countries
- Study dates
- Dec 2014to Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
35 sites in 9 countries.
35 sites in 9 countries
United States12 sites
University of Maryland
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Boston University Medical Center
Boston, Massachusetts, 02118
University of Cincinnati
Cincinnati, Ohio, 45267
Ohio State University Medical Center
Columbus, Ohio, 43221
UT Southwestern
Dallas, Texas, 75390
University of Texas, Houston Center for Clinical and Translational Sciences
Houston, Texas, 77030
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Pittsburg Medical Center
Pittsburgh, Pennsylvania, 15229
UC Davis Medical Center
Sacramento, California, 95817
UCLA Medical Center
Torrance, California, 90502
Australia5 sites
The Prince Charles Hospital
Chermside, 4032
St Vincent's Hospital
Darlinghurst, 2010
St Vincent's Hospital
Fitzroy, 3065
Royal Hobart Hospital
Hobart, 7000
Fiona Stanley Hospital
Murdoch, 6150
Hungary3 sites
Gottsegen György Országos Kardiologiai Intézet, Felnőtt Kardiológia
Budapest, 1096
Semmelweis Egyetem Pulmonológiai Klinika
Budapest, 1125
Pécsi Tudományegyetem Klinikai Központ, Szívgyógyászati Klinika
Pécs, 7624
Poland3 sites
Uniwersytecki Szpital Kliniczny w Białymstoku
Bialystok, 15-276
Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie
Krakow, 31-202
Wojewódzki Szpital Specjalistyczny im. W. Biegańskiego w Łodzi
Lodz, 91-347
Romania3 sites
Institutul de Urgență pentru Boli Cardiovasculare, Secția Clinică Cardiologie III
Bucharest, 022322
Institutul de Pneumoftiziologie "Marius Nasta", Secția Clinică Pneumoftiziologie IV
Bucharest, 050159
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie, Sectia Clinica Pneumologie II
Timișoara, 300310
Serbia3 sites
Klinički Centar Srbije (KCS), Klinika za kardiologiju
Belgrade, 11000
Kliničko-bolnički centar (KBC) Zemun,Klinika za internu medicinu,Sluzba kardiologije
Belgrade, 11080
Institut za plućne bolesti Vojvodine Sremska Kamenica (IPBVSK),
Kamenitz, 21204
Spain3 sites
Hospital Universitari General Vall d'Hebron, Servicio de Neumología
Barcelona, 08035
Hospital Clinic de Barcelona, Departamento de Pneumologia
Barcelona, 11000
Hospital 12 de Octubre, Departamento de Cardiologia
Madrid, 28041
Bulgaria2 sites
"Многопрофилната болница за активно лечение "Национална кардиологична болница "" ЕАД
Sofia, 1309
Многопрофилна болница за активно лечение "Света Анна" София АД, Клиника по кардиология
Sofia, 1750
Czechia1 site
II. interní klinika - klinika kardiologie a angiologie, 1. lékařská fakulta, Univerzita Karlova v Praze a Všeobecná fakultní nemocnice v Praze
Prague, 12808
About this study
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
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.
Read the 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.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- APD811, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APD811Drug
Also called Ralinepag
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| APD811 | Experimental | Multiple dose titration to maximum tolerated dose. Receives: Drug: APD811 |
| Placebo | Placebo comparator | Multiple dose titration to maximum tolerated dose. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 22 Weeks
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).
Measured: Baseline and 22 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2014 (estimated)
- Study startDec 2014
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by United TherapeuticsThe 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Derek Solum, PhD, Study director, United Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02279160
- Sponsor's protocol ID
- APD811-003
- Status last verified
- Jun 2020
- First submitted
- 25 Oct 2014
- Last updated
- 14 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 31391223
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02279160
- Acronym / sponsor ID
- APD811-003
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 30 Oct 2014 (estimated)
- Results
- Posted 14 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| APD811 | Experimental | Drug: APD811Multiple dose titration to maximum tolerated dose. |
| Placebo | Placebo comparator | Drug: PlaceboMultiple dose titration to maximum tolerated dose. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Males or females aged 18-75 years, inclusive
- Symptomatic WHO Group 1 PAH classified by one of the following subgroups:
- 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
Key exclusion criteria (8 listed)
- 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
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 |
|---|---|---|
| APD811Also: Ralinepag | Drug | APD811 |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Change From Baseline in Pulmonary Vascular Resistance (PVR)
Time frame: Baseline and 22 Weeks
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
Time frame: Baseline and 22 Weeks
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31391223Torres 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.
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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.
Derek Solum, PhD study director
United Therapeutics
35 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APD811 in people with Pulmonary Arterial Hypertension, run by United Therapeutics at 35 sites in 9 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 13 inclusion and 8 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: finished, as of the sponsor's last update on 14 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Australia, Hungary, Poland, Romania and 4 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?
Yes. Results are posted in the registry (first posted 14 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Pulmonary Vascular Resistance (PVR) (time frame: Baseline and 22 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02279160, which also lists 1 linked publication.
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 14 Jul 2020.