Long-term Safety and Efficacy of Ralinepag in Pulmonary Arterial Hypertension

NCT ID: NCT02279745

Last Updated: 2021-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-08
• Study Completion Date: 2021-03-29

Brief Summary

This study was an open-label extension study to determine the long-term safety and tolerability of ralinepag in subjects with World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH) who have completed Study APD811-003, or who were assigned to receive placebo and were discontinued due to clinical worsening.

Detailed Description

This study was an open-label extension study to determine the long-term safety and tolerability of ralinepag in subjects with WHO Group 1 PAH who completed Study APD811-003. Subjects who completed Study APD811-003 and met eligibility criteria for Study APD811-007 were enrolled. Additionally, placebo-treated subjects who discontinued study drug treatment due to clinical worsening in Study APD811-003 were permitted to enroll in Study APD811-007, upon approval of the medical monitor, provided that all end of study procedures including right heart catheterization (RHC) were performed per the study protocol. The Week 25 Visit in Study APD811-003 served as the Baseline Visit for Study APD811-007.

All subjects enrolled in Study APD811-007 received open-label treatment with ralinepag. The starting dose and titration schedule were individually determined and in accordance with the starting dose and titration schedule optimized from Study APD811-003. Adjustments in the dose and titration schedule were made according to subject tolerability.

After an individual subject completed Study APD811-003 and that subject's database was locked, subject unblinding occurred. Subjects on active treatment (ralinepag) remained on their current dose and had onsite clinical assessments performed every 3 months until the subject was discontinued from the study.

Subjects in the placebo treatment group underwent a dose titration period until a stable, maximum tolerated dose (MTD) was reached (up to 9 weeks), followed by a treatment period after the MTD was determined during which monthly onsite clinic assessments were performed for the first 3 months and then every 3 months until the subject was discontinued from the study or the study was terminated. Dose reductions could be made at any time for safety reasons. Incremental dose increases were also allowed during the Treatment Period at the discretion of the Investigator (as clinically indicated) and according to the stepwise titration scheme.

Subjects were assessed for clinical worsening during each clinic visit. If clinical worsening was confirmed, the Investigator could have opted to either continue treatment with ralinepag at the current dose, increase the dose of ralinepag, interrupt treatment, or discontinue the subject at his/her discretion.

In addition, attempts were made to contact all subjects at the time of Study APD811-007 termination to assess their vital (mortality) status. After the last subject enrolled in Study APD811-007 completed approximately 6 months of the study, a cumulative all-subject data analysis was performed for all subjects who entered the study. Subjects continued to have visits to the clinic every 3 months until the Sponsor discontinued the study. At the time of the Sponsor's decision to discontinue the study, all ongoing subjects completed an End of Study Visit. A 28-day Follow-up Visit was conducted to ensure appropriate subject safety. Subjects who remained on ralinepag were eligible to transition into the Phase 3 open-label extension study (ROR-PH-303) prior to APD811-007 study termination. For those subjects that did not enroll in Study ROR-PH-303, a 28-day Follow-up Visit was conducted to evaluate ongoing subject safety, including survival status.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral Ralinepag

Ralinepag immediate-release (IR) capsules of 10, 20, 30, 40, and 100 mcg or extended-release (XR) tablets of 50, 250, and 400 mcg for oral administration.

Group Type: EXPERIMENTAL

Ralinepag

Intervention Type: DRUG

Active

Interventions

Ralinepag

Active

Intervention Type: DRUG

Other Intervention Names

APD811

Eligibility Criteria

Inclusion Criteria

• Evidence of a personally signed and dated informed consent document.
• Was willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and was deemed an appropriate candidate for participation in a long-term extension study.
• Female subjects were nonpregnant, nonlactating, surgically sterile or postmenopausal, or agreed to use an accepted method of birth control for at least 3 months prior to the first dose, during, and for at least 30 days after the last dose of study drug.
• Male subjects were either surgically sterile or agreed to use a condom with spermicide when sexually active with a female partner who was not using an acceptable method of birth control during the study and for 30 days after the last dose of study drug.
• Male and female subjects agreed not to participate in a conception process during the study and for 30 days after the last dose of study drug.
• Fulfilled all eligibility criteria for Study APD811-003 and completed the study as planned.

Subjects who were assigned to placebo in Study APD811-003 and experienced clinical worsening in that study could enroll in Study APD811-007 after completing all end of study procedures per protocol, including RHC, for Study APD811-003 and had their data locked.

Exclusion Criteria

• Subjects who enrolled in Study APD811-003 and were withdrawn from study drug treatment due to any adverse event (AE), serious adverse event (SAE), or subjects who did not complete Study APD811003, with the exception made for placebo-treated subjects who experienced a clinical worsening event.
• Female •subjects who wished to become pregnant.
• Systolic blood pressure <90 mmHg at Baseline.
• Other severe acute or chronic medical or laboratory abnormalities that could have increased the risk associated with study participation or investigational product administration or interfered with the interpretation of study results and, in the judgment of the investigator, would have made the subject inappropriate for entry into this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Cedars-Sinai Medical Center

Beverly Hills, California, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

University of California Davis Medical Center

Sacramento, California, United States

Harbor-UCLA Medical Center

Torrance, California, United States

University of Colorado Cardiac and Vascular Center, Anschutz Inpatient Pavilion

Aurora, Colorado, United States

Cleveland Clinic Florida

Weston, Florida, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Chest Medicine Associates

Portland, Maine, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Boston University Medical Center General Clinical Research Unit (GCRU)

Boston, Massachusetts, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

UC Health

Cincinnati, Ohio, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center - Martha Morehouse Medical Pavilion

Columbus, Ohio, United States

UPMC, Presbyterian

Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Memorial Hermann Hospital - Texas Medical Center

Houston, Texas, United States

St. Vincent's Hospital

Darlinghurst, New South Wales, Australia

The Prince Charles Hospital

Chermside, Queensland, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

St Vincent's Hospital

Fitzroy, Victoria, Australia

Fiona Stanley Hospital

Murdoch, , Australia

Multiprofile Hospital for Active Treatment "National Heart Hospital" EAD, Clinic of Cardiology

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment " St. Anna", Sofia AD, Cardiology Clinic

Sofia, , Bulgaria

Department of Internal Medicine I - Cardiology, University Hospital Olomouc

Olomouc, , Czechia

Second Internal Clinic - Clinic of Cardiology and Angiology, 1st Faculty of Medicine, Charles University in Prague, General University Hospital in Prague

Prague, , Czechia

Gottsegen Gyorgy Orszagos Kardiológiai lntézet - National Institute of Cardiology, Department of Adult Cardiology

Budapest, , Hungary

Semmelweis University, Department of Pulmonology - Semmelweis Egyetem Pulmonológiai Klinika

Budapest, , Hungary

University of Szeged Faculty of Medicine, 2nd Department of Medicine and Cardiology Center, Albert Szent-Györyi Clinical Center - SZTE ÁOK Szent-Györgyi A lbert Klinikai Központ I I. sz. Belgyógyászati Klini ka és Kard ilógiai Központ

Budapest, , Hungary

University of Pecs, Medical School, Heart Institute - Pécsi Tudományegyetem, Klinikai Központ, Szívgyógyászati Klinika

Budapest, , Hungary

University of Derecen Clinical Research Center Cardiology and Cardiac Surgery Department - Debreceni Egyetem Klinikai Kozpont Kardiologiai es Szivsebeszeti Klinika

Debrecen, , Hungary

Medical University of Bialystok Clinical Hospital Cardiology Clinic - Uniwersytecki Szpital Kliniczny, Klinika Kardiologii z Oddziałem Intensywnego Nadzoru Kardiologicznego

Krakow, , Poland

John Paul II Hospital in Cracov Department of Cardiac and Vascular Diseases - Krakowski Szpital Specjalistyczny im. Jana Pawła II, Oddział Kliniczny Chorób Serca i Naczyń

Krakow, , Poland

Biegański Provincial Specialist Hospital Department of Cardiology - Wojewódzki Szpital Specjalistyczny im. dr Wł. Biegańskiego w Lodzi, Oddział Kardiologiczny

Lodz, , Poland

"Prof. Dr. C.C. Iliescu" Institute of Cardiovascular Diseases, Department of Clinic Cardiology III - Institutul de Urgenţă pentru Boli Cardiovasculare "Prof. Dr. C.C. Iliescu", Secţia Clinica Cardiologie fIJ

Bucharest, , Romania

"Marius Nasta" Institute of Pneumoftiziology, Department of Pneumoftiziology IV - Institutul de Pneumoftiziologie "Marius Nasta", Sectia Clinica Pneumoftiziologie IV

Bucharest, , Romania

"Dr. Victor Babes" Clinic Hospital for Infesctious Diseases and Pneumoftiziology, Department of Clinic Pneumology II

Timișoara, , Romania

Clinical Centre of Serbia (CCS), Cardiology Clinic - Klinicki Centar SrЬije, Klinika za kardiologiju

Belgrade, , Serbia

Кlinicko-bolnicki Centar Zemun, Кlinika za internu medicinu, Sluzba za kardiologiju

Belgrade, , Serbia

Institut za plucne bolesti Vojvodine Sremska Kamenica, Klinika za urgcntnu pulmologiju, Odeljcnje intenzivne nege - Institute of Pulmonary Diseases of Vojvodina Sremska Kamenica (IPDVSK), The Clinic for Urgent Pulmonology, ICU - Intensive Care Unit

Kamenitz, , Serbia

Department of Heart Failure and Transplantation, National Institute of Cardiovascular Diseases - Oddelenie zlyhávania a transplantácie srdca, Národný ústav srdcových a cievnych chorôb, a.s.

Bratislava, , Slovakia

Cardiology department, East Slovak Institute for Cardiovascular Diseases - Kardiologické oddelenie Klinika kardiológie , Východoslovenský ústav srdcových a cievnych chorôb, a.s

Košice, , Slovakia

Clinic Hospital of Barcelona, Department of Pneumology

Barcelona, , Spain

General University Hospital Vall d'Hebron, Department of Pneumology

Barcelona, , Spain

Hospital 12th of October, Department of Cardiology

Madrid, , Spain

Countries

United States; Australia; Bulgaria; Czechia; Hungary; Poland; Romania; Serbia; Slovakia; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

APD811-007

Identifier Type: -

Identifier Source: org_study_id