Clinical Trial: Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A 16-Week, Open-Label, Multi-Center, Parallel, Randomized Controlled Study to Compare the Safety, Tolerability, Pharmacokinetics and Efficacy of Slow and Rapid Dose Titration Regimens of Subcutaneous

Brief Summary: This is an open-label, multicenter, parallel, randomized (1:1 Slow Dose Titration Group; Rapid Dose Titration Group), two-group study to evaluate the safety, tolerability, pharmacokinetics and efficacy of slow and rapid dose titration regimens of subcutaneous Remodulin infusion in subjects with pulmonary arterial hypertension (PAH). The study will include about 50 subjects at up to 10 clinical trial centers in China. The treatment phase of the study will last approximately 16 weeks. Subjects who complete all required assessments will also be eligible to enter a long-term open-label, extension study (CVT-CV-004).

Detailed Summary:
Sponsor: United Therapeutics

Current Primary Outcome:

  • Incidence of Adverse Events Among Subjects through 16 Weeks [ Time Frame: 16 Weeks ]
    The incidence of adverse events among subjects throughout the 16 week study will be measured by the number of subjects analyzed and the percentage of those subjects who experienced an adverse event.
  • Change in Patient Reported Site Pain from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    The site pain questionnaire is a 10-point scale rating the worst site pain experienced on a measured day. Scores will range from 0 (no pain) to 10 (worst possible pain). The questionnaire will be completed each time a new infusion site is placed and until a subject's infusion site pain level reaches a score of zero for two consecutive days or they have completed 14 days. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Incidence of Subject Discontinuations Among Participants through 16 Weeks [ Time Frame: 16 Weeks ]
    The incidence of subject discontinuations among subjects throughout the 16 week study will be measured by the number of subjects analyzed and the percentage of those participants who discontinued.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in 6-minute Walk Distance (6MWD) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline to Week 16, correlates with the current clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS). Subjects will be instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes. 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. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Change in Borg Dyspnea Score (following 6MWT) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    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 will be assessed immediately following the 6MWT. Scores range from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced). Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    The N-terminal pro-BNP (NT-proBNP) serum concentration will be assessed as a biomarker to compare the severity of heart failure at Baseline and Week 16. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Number of Participants with a Change from Baseline World Health Organization (WHO) Functional Classification at Week 16 [ Time Frame: Change from Baseline at Week 16 ]
    The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: 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. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Change in PAH Symptoms from Baseline to Week 16 [ Time Frame: Change from Baseline at 16 Weeks ]
    Symptoms of PAH including fatigue, dyspnea, edema, dizziness, syncope, chest pain and orthopnea will be assessed and if present, the intensity of the symptom will be rated as mild, moderate, or severe. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Change in Measured Tricuspid Annular Plane Systolic Excursion (TAPSE) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    Change in right ventricular function will be assessed using the tricuspid annular plane systolic excursion (TAPSE) as determined by echocardiography. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Change in Measured Tricuspid Regurgitant Jet Velocity (TRJV) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    Change in right ventricular function will be assessed using the tricuspid regurgitant jet velocity (TRJV) as determined by echocardiography. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Incidence of Pericardial Effusion from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    Change in right ventricular function will be assessed by the presence or absence of pericardial effusion as determined by echocardiography. Changes from Baseline to Week 16 will be summarized and compared between treatment groups using descriptive statistics. No formal hypothesis testing will be performed.
  • Measure treprostinil plasma concentration from Week 4 to Week 16 [ Time Frame: Week 4, Week 8, Week 12, and Week 16 ]
    During the treatment phase at Weeks 4, 8, 12, and 16 or at the time of premature study termination, a single blood sample will be collected to measure treprostinil plasma concentration.


Original Secondary Outcome: Same as current

Information By: United Therapeutics

Dates:
Date Received: August 24, 2016
Date Started: February 2017
Date Completion: April 2018
Last Updated: May 8, 2017
Last Verified: May 2017