A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH

(CAPACITY Trial)

Recruiting at 37 trial locations

Overseen By United Therapeutics Global Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: United Therapeutics

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 28 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called ralinepag to see if it can help people with Pulmonary Arterial Hypertension (PAH) exercise better. The medication works by improving blood flow in the lungs, making it easier for the heart to pump blood. The study will measure changes in exercise ability after several months of treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current PAH-specific oral therapy for at least 90 days before joining. If you're taking other medications that might affect PAH, those doses should be stable for at least 30 days before starting, except for diuretics, which need to be stable for 10 days.

What safety data exists for the treatment known as Ralinepag?

The available research does not provide specific safety data for Ralinepag, but it highlights the importance of adverse drug event reporting systems and databases like ChEMBL and MetaADEDB for monitoring drug safety. These resources collect and update information on adverse effects, which can help assess the safety of various drugs, including those evaluated under different names or for different conditions. ^{1 2 3 4 5}

Eligibility Criteria

Inclusion Criteria

You have provided a signed consent form.

You are displaying WHO/NYHA FC II to III symptoms.

You have a peak VO2 between 9 and 18 mL/min/kg, as determined by the CPET core laboratory.

Exclusion Criteria

For subjects with known human immunodeficiency virus-associated PAH, a cluster of differentiation 4 T-cell count <200/mm3 at Screening.

Has evidence of more than mild lung disease on pulmonary function tests performed within 1 year prior to, or during, Screening.

Has evidence of thromboembolic disease as determined by ventilation-perfusion lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ralinepag or placebo for 28 weeks to evaluate effects on exercise capacity

28 weeks

Visits at Baseline, Weeks 4, 8, 12, 16, 20, 24, and 28

Follow-up

Participants are monitored for survival status every 6 months if they discontinue or do not enter the open-label extension

6 months

Open-label extension (optional)

Participants may opt into continuation of ralinepag treatment long-term

Treatment Details

Interventions

• Ralinepag

Participant Groups

Group I: Ralinepag Experimental Treatment 1 Intervention

Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the individual maximum tolerated dose (maximum dose of 1400 mcg)

Group II: Placebo Placebo Group 1 Intervention

Matching placebo tablets (oral)

Who Is Running the Clinical Trial?

United Therapeutics

Lead Sponsor

Trials

112

Recruited

14,500+

Dr. Martine Rothblatt

United Therapeutics

Chief Executive Officer since 1996

PhD in Medical Ethics from the Royal London College of Medicine and Dentistry, JD and MBA from UCLA

Dr. Michael Benkowitz

United Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Findings from Research

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

A systematic review of 108 adverse drug event (ADE) reporting systems revealed 1782 unique data fields, highlighting significant variability in how ADEs are reported, which complicates data comparison and aggregation across different systems.

Despite consistent reporting concepts, the lack of standardized terminology and the use of multiple drug and disease dictionaries hinder effective drug safety monitoring, suggesting a need for a common standardized dataset to improve ADE reporting and surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug event reporting systems: a systematic review. Bailey, C., Peddie, D., Wickham, ME., et al.[2021]

MetaADEDB 2.0 is an updated online database that now includes 744,709 drug-adverse drug event (ADE) associations, representing a 40% increase from its previous version, making it a more comprehensive resource for researchers.

The new version features a user-friendly web interface, enhancing accessibility for drug safety assessments and studies in drug discovery and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. Yu, Z., Wu, Z., Li, W., et al.[2021]

The over-reporting of serious adverse events (SAEs) during clinical trials can obscure true safety signals and burden sponsors, investigators, and FDA reviewers, potentially endangering patient safety.

A working group from LUNGevity Foundation suggests that 'anticipated' SAEs related to lung cancer should not be reported individually to the FDA, but rather analyzed in aggregate, which could streamline reporting and improve safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing Uninformative IND Safety Reports: A List of Serious Adverse Events anticipated to Occur in Patients with Lung Cancer. Bonomi, P., Stuccio, N., Delgra, CJ., et al.[2021]

A new standardized strategy for reporting adverse events (AEs) and serious adverse events (SAEs) in substance use disorder (SUD) clinical trials was developed, which aims to reduce the reporting burden while maintaining safety monitoring.

In a review of 17 SUD trials involving 6737 participants, the new strategy showed a significant reduction in irrelevant safety event reporting, leading to a more consistent safety assessment system tailored to the risks associated with specific trial interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for safety reporting in substance abuse trials. Lindblad, R., Campanella, M., Styers, D., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Adverse drug event reporting systems: a systematic review. [2021]

3. England pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Reducing Uninformative IND Safety Reports: A List of Serious Adverse Events anticipated to Occur in Patients with Lung Cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Strategies for safety reporting in substance abuse trials. [2013]