Long Term Safety and Efficacy of Ralinepag in Pulmonary Arterial Hypertension

• ClinicalTrials.gov Identifier: NCT02279745
• Recruitment Status: Active, not recruiting
• First Posted: October 31, 2014
• Last Update Posted: July 23, 2019
• Sponsor: United Therapeutics
• Information provided by (Responsible Party): United Therapeutics

Study Description

Brief Summary:

This study is an open-label extension study to determine the long-term safety and tolerability of APD811 in patients with WHO Group 1 PAH who have completed the Phase 2 study, APD811-003. Patients must have completed the APD811-003 study and must meet eligibility criteria for APD811-007.

Condition or disease	Intervention/treatment	Phase
Pulmonary Arterial Hypertension	Drug: Ralinepag	Phase 2

Detailed Description:

This study is an open-label extension study to determine the long-term safety and tolerability of APD811 in patients with WHO Group 1 PAH who have completed the Phase 2 Study APD811-003. Patients must have completed Study APD811-003 and met eligibility criteria for Study APD811-007. Additionally, placebo-treated patients who discontinue study drug treatment due to clinical worsening in Study APD811-003 will be permitted to enroll in Study APD811-007, upon approval of the medical monitor, provided that all end of study procedures including right heart catheterization are performed per protocol. The Week 25 Visit in Study APD811-003 will serve as the Baseline Visit for Study APD811-007.

All patients enrolled in Study APD811-007 will receive open-label treatment with APD811. The starting dose and titration schedule will be individually determined and in accordance with the starting dose and titration schedule optimized from Study APD811-003. Adjustments in the dose and titration schedule may be made according to patient tolerability.

After an individual patient completes Study APD811-003 and that patient's database is locked, patient unblinding will occur. Patients on active treatment (APD811) will remain on current dose and have onsite clinical assessments performed every 3 months until the patient is discontinued from the study.

Patients in the placebo treatment group will undergo a dose titration period until a stable, maximum tolerated dose (MTD) is reached (up to 9 weeks), followed by a treatment period after the MTD is determined during which monthly onsite clinic assessments will be performed for the first 3 months and then every 3 months until the patient is discontinued from the study or the study is terminated (see Table 2).

Discontinuation of the study may also occur at Sponsor's decision to terminate the study. Dose reductions may be made at any time for safety reasons.

Incremental dose increases will also be allowed during the Treatment Period at the discretion of the investigator (as clinically indicated) and according to the stepwise titration scheme. Uptitration should not occur within 6 weeks of an efficacy assessment.

Patients will be assessed for clinical worsening during each clinic visit. If clinical worsening is confirmed, the Investigator may opt to either continue treatment with APD811 at the current dose, increase the dose of APD811, interrupt treatment, or discontinue the patient at his/her discretion.

In addition, all patients will be contacted yearly following discontinuation in Study APD811-007 to assess mortality status. The mortality status follow-up contact of patients who withdraw consent will depend on local regulations or specific agreement with the subject and investigator.

After the last patient enrolled in Study APD811-007 has completed approximately 6 months of the study, a cumulative all-patient data analysis will be performed for all patients who entered the study. Patients will continue to have visits to the clinic every 3 months indefinitely to collect data until marketing approval of APD811 is granted or until the Sponsor discontinues the study. At the time of marketing approval or the Sponsor's decision to discontinue the study, all on-going patients will complete an End of Study Visit. A 28-day Follow-up Visit will be conducted to ensure appropriate subject safety.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Extension Study of Ralinepag in Patients With Pulmonary Arterial Hypertension
• Study Start Date: July 2015
• Estimated Primary Completion Date: September 2019
• Estimated Study Completion Date: September 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ralinepag; Ralinepag immediate release (IR) capsules of 0.01, 0.02, 0.03, 0.04 mg, and 0.10 mg per capsule or extended release (XR) tablets of 50, 250, and 400 mcg (0.05, 0.25 and 0.4 mg) for oral administration. The starting dose and titration schedule will be determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003.	Drug: Ralinepag; Active; Other Name: APD811

Outcome Measures

Primary Outcome Measures :

1. Long-term safety assessed by adverse events up to 28 days following discontinuation of study drug [ Time Frame: From Baseline to 28 days following discontinuation of study drug. ]
   The number of adverse events will be computed overall and by treatment group in the parent study (Study APD811-003)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document

• Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and is deemed an appropriate candidate for participation in a long-term extension study and administration of APD811

  • Fulfilled all eligibility criteria for APD811-003 and completed the study as planned
  • Patients who discontinued for clinical worsening in APD811-003 and were assigned to placebo and completed all end of study procedures including right heart catheterization (RHC) may participate after their data from the APD811-003 study is cleaned and locked

Exclusion Criteria:

• Patients who enrolled in APD811-003 and were withdrawn from study drug treatment due to any AE, SAE, or clinical worsening if assigned to APD811, or patients who did not complete the APD811 003 study for other reasons.
• Female patients who wish to become pregnant
• Systolic BP <90 mmHg at Baseline/Day 1
• 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

Contacts and Locations

  Show 47 Study Locations

Sponsors and Collaborators

United Therapeutics

Investigators

• Study Director: Isil Saib, MPH; United Therapeutics

More Information

• Responsible Party: United Therapeutics
• ClinicalTrials.gov Identifier: NCT02279745 History of Changes
• Other Study ID Numbers: APD811-007
• First Posted: October 31, 2014
• Last Update Posted: July 23, 2019
• Last Verified: July 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Familial Primary Pulmonary Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases