This was a multicenter, randomized (1:1 inhaled treprostinil: placebo), double-blinded, placebo-controlled trial to evaluate the safety and efficacy of inhaled treprostinil in subjects with pre-capillary pulmonary hypertension (PH) associated with interstitial lung disease (ILD) including combined pulmonary fibrosis and emphysema (CPFE). The study included 326 patients at approximately 120 clinical trial centers. The treatment phase of the study lasted approximately 16 weeks. Patients who completed all required assessments were eligible to enter an open-label, extension study (RIN-PH-202).
Study RIN-PH-201 was a multicenter, randomized, double-blind, placebo controlled, 16 week, parallel group study designed to investigate the safety and efficacy of inhaled treprostinil in subjects with PH-ILD. Subjects initiated inhaled treprostinil or placebo at a dose of 3 breaths (18 mcg) 4 times daily (QID) (during waking hours). Study drug doses were maximized throughout the study. Dose escalations (additional 1 breath QID) could occur up to every 3 days with a target dosing regimen of 9 breaths (54 mcg) QID and a maximum dose of 12 breaths (72 mcg) QID, as clinically tolerated. Subjects were assessed during Screening and Baseline to determine eligibility for the study. Once eligible, 5 Treatment Phase visits to the clinic were required at Week 4, Week 8, Week 12, Week 15, and Week 16 (final study visit). An Early Termination (ET) Visit was conducted for subjects who discontinued prior to Week 16; all assessments planned for the final Week 16 Visit were conducted during the ET Visit, if applicable. Subjects were contacted at least weekly by telephone or email to assess tolerance to study drug, AEs, and changes to concomitant medications. Efficacy assessments consisted of 6-minute walk distance (6MWD), plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentration, and incidence of clinical worsening. Exploratory endpoints included change in St. George's Respiratory Questionnaire (SGRQ), change in distance saturation product (DSP), time to exacerbation of underlying lung disease, and pulmonary function tests (PFT). Safety assessments consisted of the development of AEs, vital signs, clinical laboratory parameters, ECG parameters, hospitalizations due to cardiopulmonary indications, exacerbations of underlying lung disease, and oxygenation. Subjects who remained on study drug, completed all assessments during the 16-week Treatment Phase, and met all eligibility criteria were eligible for the open-label extension study (RIN-PH-202). Additionally, subjects who withdrew from study drug prior to Week 16 due to clinical worsening and returned to the clinic for scheduled visits (excluding the Week 15 Visit) were eligible for RIN PH-202.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
326
Inhaled treprostinil (6 mcg/breath) administered four times daily
Placebo administered four times daily
University of Alabama at Birmingham
Birmingham, Alabama, United States
IMC-Diagnostic & Medical Clinic
Mobile, Alabama, United States
Arizona Pulmonary Specialists, Ltd.
Phoenix, Arizona, United States
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
University of Arizona
Tucson, Arizona, United States
Change in 6-minute Walk Distance (6MWD) Measured at Peak Exposure From Baseline to 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 PH and is considered an objective measure of patient functional status. Subjects will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Peak exposure 6MWD will occur by conducting 6-minute walk test (6MWT) within 10 to 60 minutes after the most recent dose of study drug dose.
Time frame: Baseline and Week 16
Change in Plasma Concentration of N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 16
The NT-proBNP serum concentration is a useful biomarker associated with changes in right heart morphology and function. NT-proBNP serum concentration will be assessed to compare the severity of heart failure at Baseline and Week 16. Blood for NT-proBNP assessment must be drawn prior to conducting the 6MWT.
Time frame: Baseline and Week 16
Incidence of Clinical Worsening
Subjects were monitored for clinical worsening from the time of randomization until 1 of the following criteria were met: hospitalization due to a cardiopulmonary indication; decrease in 6MWD \>15% from Baseline directly related to the disease under study, at 2 consecutive visits and at least 24 hours apart; death (all causes); or lung transplantation.
Time frame: Baseline to Week 16
Change in Peak 6-minute Walk Distance (6MWD) From Baseline to Week 12
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 12, correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status. Subjects will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Peak exposure 6MWD will occur by conducting 6MWT within 10 to 60 minutes after the most recent dose of study drug dose.
Time frame: Baseline and Week 12
Change in Trough 6-minute Walk Distance (6MWD) From Baseline to Week 15
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 15, correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status. Subjects will be instructed to walk down a corridor at a comfortable speed as far as they can 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. Trough exposure 6MWD will occur by conducting 6-minute walk test (6MWT) at least four hours after the most recent study drug dose.
Time frame: Baseline and Week 15
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Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion
Beverly Hills, California, United States
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Fresno, California, United States
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La Jolla, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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