Ralinepag Clinical Trials

What Is Ralinepag?

Uses and Conditions Under Study

• Pulmonary Hypertension: This group includes Pulmonary Arterial Hypertension, PAH, Pulmonary Hypertension, Familial Primary Pulmonary Hypertension, and Hypertension, Pulmonary. These conditions are characterized by high blood pressure in the arteries leading from the heart to the lungs, which can lead to shortness of breath, fatigue, and other serious symptoms. Ralinepag is being studied in four trials for Pulmonary Arterial Hypertension and three trials for the other related pulmonary hypertension conditions. The investigation aims to determine if Ralinepag can offer therapeutic benefits for patients with these challenging lung and heart conditions.
• Vascular and Cardiovascular Diseases: Ralinepag is also under investigation for broader Vascular Diseases, Cardiovascular Diseases, and Hypertension. These conditions involve issues with blood vessels and the heart, such as high blood pressure. The study of Ralinepag in these areas suggests an exploration of its potential effects on the overall cardiovascular system. Each of these broader categories is being studied in three trials.
• Respiratory Tract and Lung Diseases: The medication is also being explored for Respiratory Tract Disease and Lung Diseases. These conditions encompass a wide array of illnesses affecting the lungs and airways. Given Ralinepag's study in pulmonary hypertension, its investigation in these broader respiratory conditions may be related to its potential impact on lung health. Each of these is being studied in three trials.

Dosing

• Dosage Form: Ralinepag is supplied as 50 mcg round, orange, extended-release (XR) tablets for oral administration.
• Investigational Regimens: Clinical trials have explored different dosing regimens for Ralinepag, all administered in the fasted state. These regimens involve taking varying numbers of the 50 mcg XR tablets to achieve different total doses:
  • Regimen A: 1 × 50 mcg Ralinepag XR tablet (total 50 mcg)
  • Regimen B: 2 × 50 mcg Ralinepag XR tablets (total 100 mcg)
  • Regimen C: 3 × 50 mcg Ralinepag XR tablets (total 150 mcg)
  Subjects in these studies received Regimens A, B, and C in a sequential manner to evaluate the effects of different dose levels. The specific frequency of administration (e.g., once daily, twice daily) is not detailed in the provided information, but the focus is on single-arm, oral administration. All described dosing has been for adult subjects, with no specific pediatric dosing information provided.

Side Effects

Information regarding the specific side effects of Ralinepag and their frequency compared to placebo was not provided in the available clinical trial data.

Clinical Trial Results

Ralinepag has been studied in patients with Pulmonary Arterial Hypertension (PAH) in an open-label trial (NCT02279745) that evaluated its long-term safety and efficacy. These results do not include a comparison to a placebo group.

Pulmonary Arterial Hypertension (PAH)

In the study, patients receiving oral Ralinepag showed various changes in their 6-Minute Walk Distance (6MWD) from baseline. Observed median changes in 6MWD ranged from a decrease of 120 meters to an increase of 53 meters across different measurements or subgroups. Many patients experienced an improvement in their walking distance, with several median increases reported, including 41.0 meters, 38.5 meters, 47.0 meters, and 37.0 meters.

Regarding heart and lung function, patients treated with Ralinepag experienced a median reduction in Mean Pulmonary Arterial Pressure by 2.0 mmHg. Pulmonary Vascular Resistance also saw a median decrease of 52.2 dynes.sec/cm5. Cardiac Index and Cardiac Output showed no median change from baseline (0.0 L/min/m2 and -0.0 L/min, respectively).

The median time until patients experienced their first protocol-defined clinical worsening event was 56.50 weeks. This indicates that for half of the patients in the study, clinical worsening did not occur for over a year.

Currently Recruiting Trials

Clinical trials are a vital step in bringing new treatments to patients, allowing researchers to gather important information about a drug's safety and effectiveness. For Ralinepag, one study is actively seeking participants to further evaluate its potential.

The study, known as ADVANCE EXTENSION or ROR-PH-303, is an open-label extension study for Ralinepag. It is designed to evaluate the long-term efficacy and safety of Ralinepag in individuals with Pulmonary Arterial Hypertension (PAH), specifically WHO Group 1 PAH. This trial, sponsored by United Therapeutics, is a Phase 3 study with an ambitious enrollment target of 1000 participants.

To be eligible for this study, participants must have previously taken part in another Phase 2 or Phase 3 clinical trial involving Ralinepag. This ensures that those joining the extension study have prior experience with the medication and meet specific criteria for WHO Group 1 PAH. The study is open to individuals aged 18 years and older, of all genders, and does not include healthy volunteers or children. Conditions being studied include Pulmonary Arterial Hypertension, Pulmonary Hypertension, and other related cardiovascular and lung diseases.

If you have previously participated in a Ralinepag study for PAH and are interested in continuing to receive the investigational treatment, you can learn more about this trial by visiting its official listing: NCT03683186.

Where to Participate

The ADVANCE EXTENSION study for Ralinepag offers a broad geographic reach, with participation opportunities across the United States. The trial is actively recruiting at 48 sites located in 41 cities across 24 states, making it accessible to a wide range of eligible individuals.

Leading the recruitment efforts are several major medical centers. Top participating locations include:

• Boston, Massachusetts (3 sites)
• Los Angeles, California (3 sites)
• Philadelphia, Pennsylvania (2 sites)
• Houston, Texas (2 sites)
• Indianapolis, Indiana (2 sites)
• Santa Barbara, California (1 site)
• Stanford, California (1 site)
• Aurora, Colorado (1 site)
• Denver, Colorado (1 site)
• Gainesville, Florida (1 site)

Eligibility for the study requires participants to be between 18 and 18 years of age, encompassing adults of all genders. The study does not enroll healthy volunteers or children, focusing specifically on patients with WHO Group 1 Pulmonary Arterial Hypertension who have prior experience with Ralinepag in a clinical trial setting.

Development Timeline

The journey of Ralinepag began with its first clinical trial initiated on October 31, 2014. Since then, the drug has progressed through various stages of development, driven primarily by United Therapeutics, which has sponsored four of the five trials. One trial was also sponsored by Everstar Medicines (Shanghai) Limited.

Initially, Ralinepag's development explored its potential for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the focus of the development pipeline significantly expanded to address serious cardiovascular and respiratory conditions. The drug's investigation broadened to include Pulmonary Arterial Hypertension (PAH), Pulmonary Hypertension, and other related conditions like Connective Tissue Diseases, Familial Primary Pulmonary Hypertension, and various lung and vascular diseases.

Across its development, Ralinepag has been studied in a total of five clinical trials, enrolling 1,757 participants. These trials have spanned different phases, including one Phase 1 study, one Phase 2 study, and three Phase 3 studies, indicating a robust progression through the rigorous clinical development process. The latest trial for Ralinepag was initiated on November 3, 2020, demonstrating ongoing commitment to understanding its full therapeutic potential.