Safety of Transition From Selexipag to Remodulin® Then Oral Treprostinil in Symptomatic Adult PAH

A Multicenter, 16-Week, Open-label Study Evaluating the Safety of Transition From Selexipag to Remodulin® Then Oral Treprostinil in Symptomatic Subjects With Pulmonary Arterial Hypertension

This is a multicenter, single-arm trial to evaluate the safety of the transition from Selexipag to Remodulin® then Oral Treprostinil in Symptomatic Subjects with Pulmonary Arterial Hypertension (PAH). The study will include about 30 subjects at approximately 10 clinical trial centers. The treatment phase of the study will last approximately 16 weeks.

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Parenteral Remodulin (treprostinil) injection; Drug: Oral Treprostinil

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has a diagnosis of symptomatic idiopathic or heritable PAH, PAH associated with connective tissue disease, PAH associated with HIV infection, PAH associated with repaired congenital systemic-to-pulmonary shunt (at least 1 year since repair with respect to the date of providing informed consent), or PAH associated with appetite suppressant or toxin use.
2. The subject must be classified as WHO FC II or III at Baseline.
3. The subject is receiving selexipag for the treatment of WHO Group 1 PAH for a minimum of 90 days from Baseline.
4. Subject is in need of escalation of therapy, as determined by the Investigator.
5. Subject must be receiving a Food and Drug Administration (FDA)-approved PDE5-I or sGC stimulator and/or an ERA and has been at the current stable dose for at least 28 days prior to Baseline.

Exclusion Criteria:

1. The subject is receiving selexipag for any other disease or condition other than the treatment of WHO Group 1 PAH.
2. The subject has a Baseline 6MWD of less than 150 meters.
3. The subject's Baseline 6MWD has decreased more than 40% from the pre-selexipag baseline.
4. The subject has a history of ischemic heart disease (defined as either symptomatic or requiring anti-anginal therapy or experienced a documented myocardial infarction within the previous 6 months of Baseline), or a history of left sided myocardial dysfunction as evidenced by a PAWP greater than 15 mmHg or a left ventricular ejection fraction less than 40%.
5. The subject has previously been treated with any parenteral prostacyclin or oral treprostinil for a period of 90 days or more.

6. The subject has a history of 1 or more of the following signs of relevant lung disease within 180 days before Baseline:

   1. Total lung capacity less than 60% of predicted normal.
   2. Forced expiratory volume in 1 second is less than 55% of predicted normal.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Parenteral Remodulin then Oral Treprostinil

Drug: Parenteral Remodulin (treprostinil) injection; Remodulin will be provided in vial strengths of 1, 2.5, 5, and 10 mg/mL. Subjects will be admitted to the hospital and IV Remodulin will be initiated within 12 hours after the last dose of selexipag. Subjects will remain under observation in the inpatient setting for at least the first 72 hours of Remodulin administration. Subjects will be transitioned to an equivalent dose of SC Remodulin at discharge.; Other Names: Remodulin; Drug: Oral Treprostinil; Oral treprostinil will be provided as 0.125-, 0.25-, 1-, or 2.5-mg extended-release tablets. Oral treprostinil will be dosed three times daily with food.; Other Names: Orenitram

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events (AEs) through 16 Weeks	16 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in 6-minute Walk Distance (6MWD) from Baseline to Week 16	Baseline and Week 16
Change in Borg Dyspnea Score Immediately After 6-minute Walk Test (6MWT) from Baseline to Week 16	Baseline and Week 16
Change in plasma concentration of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from Baseline to Week 16	Baseline and Week 16
Change in Pulmonary Arterial Hypertension (PAH) Symptoms Score from Baseline to Week 16	Baseline and Week 16
Change in Score on Treatment Satisfaction Questionnaire for Medication (TSQM) from Baseline to Week 16	Baseline and Week 16

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2017
• Primary Completion (ANTICIPATED): September 1, 2018
• Study Completion (ANTICIPATED): September 1, 2018

Study Registration Dates

• First Submitted: January 6, 2017
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (ESTIMATE): January 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2017
• Last Update Submitted That Met QC Criteria: April 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Oral Treprostinil; 6 Minute Walk Test; Selexipag; Remodulin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-PH-207

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No