A Phase 2/3 interventional study of Inhaled Treprostinil in Pulmonary Hypertension, Interstitial Lung Disease and Combined Pulmonary Fibrosis and Emphysema, sponsored by United Therapeutics. Terminated at 92 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-12-02.
Sponsored by United Therapeutics · Phase 2/3, Interventional, and Treatment
This is a multicenter, open-label 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 will include about 266 patients who completed all required assessments in the RIN-PH-201 study at approximately 100 clinical trial centers. The study will continue Your participation in this study is voluntary and will last until you discontinue from the study or the study ends. The study will continue until each subject reaches the Week 108 visit or until inhaled treprostinil become commercially available for patients with PH associated with ILD including CPFE (whichever is sooner).
3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.
This study's enrollment of 243 is above the median of 72 across 2,118 interventional studies indexed under Lung Diseases.
Browse Lung Diseases studies →United Therapeutics is the lead sponsor of 81 studies on the registry; 6 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 14 (82%) have results posted.
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Females of reproductive potential must be non-pregnant (as confirmed by a urine pregnancy test at Baseline) and non-lactating, and will:
Exclusion Criteria:
Open-label access
Drug: Inhaled Treprostinil
Inhaled treprostinil up to 15 breaths (90 mcg) four times daily
Also known as: Tyvaso
Change in Peak 6-Minute Walk Distance (6MWD) From Baseline
The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline 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 6 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. 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 through Week 124 in RIN-PH-202 (Combined data from parent study RIN-PH-201 [NCT02630316] and this open-label extension study RIN-PH-202)
Change in Plasma Concentration of N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline
The N-terminal pro-BNP (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 each visit through Week 124. Blood for NT-proBNP assessment must be drawn prior to conducting the 6-minute walk test (6MWT).
Time frame: Baseline through Week 124 in RIN-PH-202 (Combined data from parent study RIN-PH-201 [NCT02630316] and this open-label extension study RIN-PH-202)
Change in Percent Predicted Forced Vital Capacity (FVC) From Baseline
Change in pulmonary function following inhaled treprostinil therapy will be measured by Forced Vital Capacity (FVC), calculated from a Pulmonary Function Test (PFT) performed at Baseline and Weeks 12, 48, and 108.
Time frame: Baseline and Weeks 12, 48, and 108
| Milestone | Inhaled Treprostinil |
|---|---|
| Started | 243 |
| Received inhaled treprostinil in rin-ph-202 (safety population) | 242 |
| Completed | 70 |
| Not completed | 173 |
| Withdrew: Death | 56 |
| Withdrew: Progressive disease | 12 |
| Withdrew: Adverse event | 29 |
| Withdrew: Withdrawal by subject | 41 |
| Withdrew: Protocol violation | 1 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Study terminated by sponsor | 24 |
| Withdrew: Withdrawal by sponsor prior to dose administration | 1 |
| Withdrew: Lung transplant | 5 |
| Withdrew: Lack of efficacy | 2 |
| Withdrew: Principal investigator terminated study site | 1 |
The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline 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 6 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. Peak exposure 6MWD will occur by conducting 6MWT within 10 to 60 minutes after the most recent dose of study drug dose.
| meters | Inhaled Treprostinil |
|---|---|
| Week 4 | 1.5 (-197 to 258) |
| Week 8 | 5.0 (-259 to 196) |
| Week 12 | 9.5 (-190 to 192) |
| Week 16 | 10.0 (-269 to 183) |
| Week 20 | 12.0 (-189 to 169) |
| Week 28 | 10.0 (-222 to 175) |
| Week 40 | 3.0 (-261 to 171) |
| Week 52 | 3.0 (-223 to 194) |
| Week 64 | -2.0 (-218 to 178) |
| Week 76 | -2.0 (-209 to 210) |
| Week 88 | -5.0 (-180 to 185) |
| Week 100 | -11.0 (-213 to 196) |
| Week 112 | -24.0 (-183 to 216) |
| Week 124 | -16.0 (-287 to 190) |
The N-terminal pro-BNP (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 each visit through Week 124. Blood for NT-proBNP assessment must be drawn prior to conducting the 6-minute walk test (6MWT).
| pg/mL | Inhaled Treprostinil |
|---|---|
| Week 8 | -5.10 (-9704.2 to 34,807.3) |
| Week 16 | -1.30 (-11,433.0 to 87,148.3) |
| Week 64 | 10.2 (-10,280.0 to 7306.0) |
| Week 124 | 31.90 (-4500.2 to 26,197.7) |
Change in pulmonary function following inhaled treprostinil therapy will be measured by Forced Vital Capacity (FVC), calculated from a Pulmonary Function Test (PFT) performed at Baseline and Weeks 12, 48, and 108.
| Percent Predicted FVC | Inhaled Treprostinil |
|---|---|
| Week 12 | 0.5 (-16 to 23) |
| Week 48 | 2.0 (-10 to 21) |
| Week 108 | 3.0 (-13 to 13) |
Collected over AEs were recorded throughout the course of the study from the time that each subject signed the ICF until all study assessments were completed, through the time that the study was terminated by the Sponsor (following the approval of inhaled treprostinil for use in patients with PH-ILD), up to 108 weeks.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Inhaled Treprostinil | 56/242 (23.1%) | 133/242 (55%) | 229/242 (94.6%) |
| Event | Inhaled Treprostinil |
|---|---|
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 28/242 |
| PneumoniaInfections and infestations | 21/242 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 13/242 |
| Right ventricular failureCardiac disorders | 10/242 |
| Acute kidney injuryRenal and urinary disorders | 9/242 |
| Cardiac arrestCardiac disorders | 8/242 |
| Fluid overloadMetabolism and nutrition disorders | 8/242 |
| Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders | 8/242 |
| SepsisInfections and infestations | 7/242 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 7/242 |
| Event | Inhaled Treprostinil |
|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 65/242 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 63/242 |
| HeadacheNervous system disorders | 45/242 |
| DiarrhoeaGastrointestinal disorders | 37/242 |
| DizzinessNervous system disorders | 36/242 |
| Upper respiratory tract infectionInfections and infestations | 34/242 |
| NauseaGastrointestinal disorders | 32/242 |
| FatigueGeneral disorders | 32/242 |
| PneumoniaInfections and infestations | 30/242 |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 30/242 |
Safety Population
| Age, Continuous(years) | Inhaled Treprostinil |
|---|---|
| Median | 70.0 (27 to 90) |
| Sex: Female, Male(Participants) | Inhaled Treprostinil |
|---|---|
| Female | 116 |
| Male | 126 |
| Ethnicity (NIH/OMB)(Participants) | Inhaled Treprostinil |
|---|---|
| Hispanic or Latino | 17 |
| Not Hispanic or Latino | 224 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Inhaled Treprostinil |
|---|---|
| American Indian or Alaska Native | 3 |
| Asian | 8 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 53 |
| White | 178 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Time Since Diagnosis(years) | Inhaled Treprostinil |
|---|---|
| Median | 0.51 (0.3 to 13.3) |
| Current Diagnosis(Participants) | Inhaled Treprostinil |
|---|---|
| Idiopathic interstitial pneumonia | 108 |
| Chronic hypersensitivity pneumonitis | 13 |
| Occupational lung disease | 5 |
| Combined pulmonary fibrosis and emphysema | 59 |
| Connective tissue disease | 57 |
| 6-Minute Walk Distance (6MWD)(meters) | Inhaled Treprostinil |
|---|---|
| Median | 270.0 (24 to 549) |
| N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)(pg/mL) | Inhaled Treprostinil |
|---|---|
| Median | 465.70 (10.2 to 92,852) |
3 further baseline measures are reported on the registry.
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This study is terminated, as verified in Nov 2022. You cannot join it, but the record below documents what was studied.
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