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Remodulin® to Oral Treprostinil Transition

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT01588405
First received: January 6, 2012
Last updated: April 8, 2016
Last verified: April 2016
  Purpose

This multi-center, open-label study will assess the tolerability and safety of transitioning subjects with stable Pulmonary Arterial Hypertension (PAH) from continuous intravenous (IV) or subcutaneous (SC) Remodulin infusion to oral treprostinil (UT-15C sustained release (SR) tablets).

This study will consist of an in-hospital transition phase, dose optimization/evaluation phase, and follow up phase.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: UT-15C SR
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Study of the Safety and Tolerability of Transitioning From Remodulin® to Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C. [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    Successful transition was based on the number of participants that completely transitioned to oral treprostinil by the week 4 study visit and clinically maintained on oral treprostinil treatment through Week 24.


Secondary Outcome Measures:
  • Change From Baseline in Six-minute Walk Distance at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    The purpose of the 6MWT is to evaluate exercise capacity associated with carrying out activities of daily living. Patients were instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes, resting whenever they needed. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation.

  • Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: Yes ]
    The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) experienced during the six-minute walk test (6MWT). The Borg dyspnea score was assessed immediately following the 6MWT. Scores ranged from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced).

  • Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning) and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.

  • Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: Yes ]
    Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.

  • Change in Dyspnea-fatigue Index From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: Yes ]
    The dyspnea-fatigue index has three components, each rated on a scale of 0 to 4, for the magnitude of the task that evokes dyspnea or fatigue, the magnitude of the pace (or effort) with which the task is performed and the associated functional impairment in general activities. The ratings for each component were added to form an aggregate score, which could range from 0, for the worst condition, to 12, for the best.

  • Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.

  • Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)] [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.

  • Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)] [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.

  • Change From Baseline to Week 24 in Hemodynamics Parameters: Mean Pulmonary Artery Pressure (PAPm), Mean Right Atrial Pressure (RAPm) and Mean Pulmonary Capillary Wedge Pressure (PCWPm) [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    Pulmonary hypertension (PH) is an increase in pressure in the pulmonary vasculature defined as a mean pulmonary artery pressure (PAPm) greater than 25 mmHg at rest or greater than 30 mmHg with exercise, as measured by right heart catheterization. Right Atrial Pressure (RAP) is the pressure of blood in the right atrium of the heart. Pulmonary Capillary Wedge Pressure (PCWP) is used to calculated pulmonary vascular resistance and can help guide therapeutic efficacy. The PAPm, RAPm and PCWPm values and their respective changes from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.

  • Change From Baseline to Week 24 in Hemodynamics Parameters: Arterial Oxygen Saturation (SaO2) (%) and Mixed Venous Oxygen Saturation (SvO2) (%) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    SaO2 measured by Arterial Blood Draw and Blood Gas Analyzer and SvO2 measured via Pulmonary Artery Catheter, are both Hemodynamics Parameters collected during right heart catheterization. Mixed venous oxygen saturation (SvO2) can help to determine whether the cardiac output and oxygen delivery is high enough to meet a patient's needs

  • Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Output (CO) (L/Min) [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    Cardiac Output (CO) is the volume of blood ejected by the heart per minute, as measured by right heart catheterization. The value and change from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.

  • Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Index (CI) (L/Min/m^2) [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    Cardiac Index (CI) relates the cardiac output (CO) from left ventricle to body surface area (BSA), thus relating heart performance to the size of the individual. The CI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.

  • Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance Index (PVRI) (mmHg*Min*m^2/L) [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    Pulmonary Vascular Resistance Index (PVRI) is calculated using Mean Pulmonary Arterial Pressure(PAPm), Pulmonary Capillary Wedge Pressure (PCWP) and Cardiac Index (CI ), to provide information about right ventricular overload. The PVRI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.

  • Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance (PVR) (mmHg*Min/L) [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    pulmonary vascular resistance (PVR) is the resistance the right ventricle must overcome to pump blood into the pulmonary arteries. The change in PVR values from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.


Enrollment: 33
Study Start Date: April 2012
Study Completion Date: December 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: UT-15C SR Drug: UT-15C SR
Subjects will transition in the hospital from Remodulin to UT-15C SR within 5 days of the start of the transition. The dose of Remodulin will be decreased as the dose of UT-15C SR is increased over the 5 days. Once subjects have been transitioned from Remodulin, the dose of UT-15C SR will continue to be modified / titrated to the appropriate optimal dose for that subject throughout the rest of the study.

  Eligibility

Ages Eligible for Study:   15 Years to 80 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Between 15 and 80 years of age, inclusive, weigh at least 40 kg and have a diagnosis of PAH
  • Have stable disease as confirmed by recent right heart catheterization and a Baseline 6MWD of at least 250 meters
  • Have been receiving Remodulin for at least 90 days and at a stable dose for at least 30 days prior to the Baseline visit; the dose of Remodulin must be between 25-75 ng/kg/min, inclusive
  • Must be also receiving an endothelin receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE-5i) for at least 90 days and have been at a stable dose for at least 30 days prior to Baseline

Exclusion Criteria:

  • WHO functional class III and IV subjects will be excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01588405

Locations
United States, Arizona
Arizona Pulmonary Specialists
Phoenix, Arizona, United States, 85013
University of Arizona Clinical and Translational Science (CATS) Research Center
Tucson, Arizona, United States, 85724
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43221
United States, Pennsylvania
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
United Therapeutics
Investigators
Study Chair: Cynthia Madden, MD, MPH Senior Clinical Research Physician
  More Information

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01588405     History of Changes
Other Study ID Numbers: TDE-PH-205 
Study First Received: January 6, 2012
Results First Received: August 20, 2015
Last Updated: April 8, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by United Therapeutics:
Pulmonary Arterial Hypertension
UT-15C SR
PAH

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Treprostinil
Antihypertensive Agents

ClinicalTrials.gov processed this record on December 09, 2016