Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension

NCT02279160 | Completed Phase 2 Results DMC

• 1 other identifier: APD811-003
• Study Type: interventional
• Target: 61
• Locations: 9 countries
• Sites: 35

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  Baseline and 22 Weeks

Study Arms (2)

APD811

EXPERIMENTAL

Multiple dose titration to maximum tolerated dose.

Drug: APD811

Placebo

PLACEBO COMPARATOR

Multiple dose titration to maximum tolerated dose.

Drug: Placebo

Interventions

APD811 DRUG

Also known as: Ralinepag

APD811

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (35)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43221, United States

Location

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, 15229, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

University of Texas, Houston Center for Clinical and Translational Sciences

Houston, Texas, 77030, United States

Location

The Prince Charles Hospital

Chermside, 4032, Australia

Location

St Vincent's Hospital

Darlinghurst, 2010, Australia

Location

St Vincent's Hospital

Fitzroy, 3065, Australia

Location

Royal Hobart Hospital

Hobart, 7000, Australia

Location

Fiona Stanley Hospital

Murdoch, 6150, Australia

Location

"Многопрофилната болница за активно лечение "Национална кардиологична болница "" ЕАД

Sofia, 1309, Bulgaria

Location

Многопрофилна болница за активно лечение "Света Анна" София АД, Клиника по кардиология

Sofia, 1750, Bulgaria

Location

II. interní klinika - klinika kardiologie a angiologie, 1. lékařská fakulta, Univerzita Karlova v Praze a Všeobecná fakultní nemocnice v Praze

Prague, 12808, Czechia

Location

Gottsegen György Országos Kardiologiai Intézet, Felnőtt Kardiológia

Budapest, 1096, Hungary

Location

Semmelweis Egyetem Pulmonológiai Klinika

Budapest, 1125, Hungary

Location

Pécsi Tudományegyetem Klinikai Központ, Szívgyógyászati Klinika

Pécs, 7624, Hungary

Location

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, 15-276, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie

Krakow, 31-202, Poland

Location

Wojewódzki Szpital Specjalistyczny im. W. Biegańskiego w Łodzi

Lodz, 91-347, Poland

Location

Institutul de Urgență pentru Boli Cardiovasculare, Secția Clinică Cardiologie III

Bucharest, 022322, Romania

Location

Institutul de Pneumoftiziologie "Marius Nasta", Secția Clinică Pneumoftiziologie IV

Bucharest, 050159, Romania

Location

Spitalul Clinic de Boli Infectioase si Pneumoftiziologie, Sectia Clinica Pneumologie II

Timișoara, 300310, Romania

Location

Klinički Centar Srbije (KCS), Klinika za kardiologiju

Belgrade, 11000, Serbia

Location

Kliničko-bolnički centar (KBC) Zemun,Klinika za internu medicinu,Sluzba kardiologije

Belgrade, 11080, Serbia

Location

Institut za plućne bolesti Vojvodine Sremska Kamenica (IPBVSK),

Kamenitz, 21204, Serbia

Location

Hospital Universitari General Vall d'Hebron, Servicio de Neumología

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona, Departamento de Pneumologia

Barcelona, 11000, Spain

Location

Hospital 12 de Octubre, Departamento de Cardiologia

Madrid, 28041, Spain

Location

Related Publications (1)

• 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.

  PMID: 31391223 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ralinepag

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Derek Solum, PhD
• Organization: United Therapeutics

dsolum@unither.com

919-425-8122

Study Officials

• Derek Solum, PhD

  United Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2014
• First Posted: October 30, 2014
• Study Start: December 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: July 14, 2020
• Results First Posted: July 14, 2020

Record last verified: 2020-06

Locations

AU (5); BU (2); CZ (1); SE (3); ES (3); US (12); RO (3); PL (3); HU (3)