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Trial record 2 of 2 for:    RIN-PH-201

Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02630316
Recruitment Status : Completed
First Posted : December 15, 2015
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Tracking Information
First Submitted Date  ICMJE December 11, 2015
First Posted Date  ICMJE December 15, 2015
Last Update Posted Date June 2, 2020
Actual Study Start Date  ICMJE February 3, 2017
Actual Primary Completion Date December 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2015)
Change in 6-minute Walk Distance (6MWD) Measured at Peak Exposure 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 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. 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2020)
  • Change in Plasma Concentration of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    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 Week 16. Blood for NT-proBNP assessment must be drawn prior to conducting the 6-minute walk test (6MWT).
  • Time to Clinical Worsening [ Time Frame: Baseline to Week 16 ]
    Subject were monitored for time to clinical worsening as 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.
  • Change in Peak 6-minute Walk Distance (6MWD) from Baseline to Week 12 [ Time Frame: Baseline and 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. 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 6-minute walk test (6MWT) within 10 to 60 minutes after the most recent dose of study drug dose.
  • Change in Trough 6-minute Walk Distance (6MWD) from Baseline to Week 15 [ Time Frame: Baseline and 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2015)
  • Change in Peak 6-minute Walk Distance (6MWD) from Baseline to Week 12 [ Time Frame: Baseline and 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. 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 6-minute walk test (6MWT) within 10 to 60 minutes after the most recent dose of study drug dose.
  • Change in Trough 6-minute Walk Distance (6MWD) from Baseline to Week 15 [ Time Frame: Baseline and 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.
  • Change in Plasma Concentration of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    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 Week 16. Blood for NT-proBNP assessment must be drawn prior to conducting the 6-minute walk test (6MWT).
  • Change in Forced Expiratory Volume (FEV1) in One Second from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    Change in pulmonary function following inhaled treprostinil therapy will be measured by Forced Expiratory Volume in One Second (FEV1), the maximal amount of air forcefully exhaled in 1 second, calculated from a Pulmonary Function Test (PFT) performed at Baseline and Week 16.
  • Change in Forced Vital Capacity (FVC) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    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 Week 16.
  • Change in Total Lung Capacity (TLC) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    Change in pulmonary function following inhaled treprostinil therapy will be measured by Total Lung Capacity (TLC), calculated from a Pulmonary Function Test (PFT) performed at Baseline and Week 16.
  • Change in Lung Diffusion Capacity (DLCO) from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
    Change in pulmonary function following inhaled treprostinil therapy will be measured by Lung Diffusion Capacity (DLCO), calculated from a Pulmonary Function Test (PFT) performed at Baseline and Week 16.
  • Incidence of Adverse Events Among Participants through 16 Weeks [ Time Frame: 16 Weeks ]
    The incidence of adverse events among participants throughout the 16 week study will be measured by the number of participants analyzed and the percentage of those participants who experienced an adverse event.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE
Official Title  ICMJE A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Subjects With Pulmonary Hypertension Due to Parenchymal Lung Disease
Brief Summary This is 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 will include about 314 patients at approximately 120 clinical trial centers. The treatment phase of the study will last approximately 16 weeks. Patients who complete all required assessments will also be eligible to enter an open-label, extension study (RIN-PH-202).
Detailed Description 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 6MWD, plasma NT-proBNP concentration, and time to clinical worsening. Exploratory endpoints included change in SGRQ, change in DSP, time to exacerbation of underlying lung disease, and PFTs. 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Pulmonary Hypertension
  • Interstitial Lung Disease
  • Combined Pulmonary Fibrosis and Emphysema
Intervention  ICMJE
  • Drug: Inhaled Treprostinil
    Inhaled treprostinil (6 mcg/breath) administered four times daily
    Other Name: Tyvaso
  • Drug: Placebo
    Placebo administered four times daily
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Matching placebo inhaled using an ultrasonic nebulizer four times daily
    Intervention: Drug: Placebo
  • Active Comparator: Active Inhaled Treprostinil
    Active Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled four times daily and titrated up to a maximum of 12 breaths four times daily
    Intervention: Drug: Inhaled Treprostinil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 7, 2020)
326
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2015)
314
Actual Study Completion Date  ICMJE December 26, 2019
Actual Primary Completion Date December 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject voluntarily gives informed consent to participate in the study.
  2. Males and females aged 18 years or older at the time of informed consent.

    a. Females of reproductive potential must be non-pregnant (as confirmed by a urine pregnancy test at screening) and non-lactating, and will: i. Either abstain from intercourse (when it is in line with their preferred and usual lifestyle), or ii. Use two medically acceptable, highly-effective forms of contraception for the duration of study, and at least 30 days after discontinuing study drug.

    b. Males with a partner of childbearing potential must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.

  3. The subject has a confirmed diagnosis of WHO Group 3 PH based on CT imaging, which demonstrates evidence of diffuse parenchymal lung disease performed within 6 months prior to randomization. Subjects may have any form of ILD or CPFE.
  4. Subjects are required to have a right heart catheterization (RHC) within one year prior to randomization with the following documented parameters:

    1. Pulmonary vascular resistance (PVR) > 3 Wood Units (WU) and
    2. A pulmonary capillary wedge pressure (PCWP) of < 15 mmHg and and
    3. A mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg
  5. Baseline 6MWD ≥ 100 meters
  6. Subjects on a chronic medication for underlying lung disease (ie, pirfenidone, nintedanib, etc) must be on a stable and optimized dose for ≥ 30 days prior to randomization. Subjects receiving pirfenidone or nintedanib must have been receiving treatment for at least 90 days and on a stable dose for at least 30 days prior to randomization.
  7. In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing and likely to be cooperative with protocol requirements, including attending all study visits.
  8. Subjects with connective tissue disease (CTD) must have a Baseline FVC of < 70%.

Exclusion criteria:

  1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons other than WHO Group 3 PH-ILD as outlined in inclusion criterion 3.
  2. The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy.
  3. The subject has received any PAH approved therapy including: prostacyclin therapy (i.e., epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), IP receptor agonist (selexipag), endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE-5I), or soluble guanylate cyclase (sGC) within 60 days of randomization.
  4. The subject has evidence of clinically significant left-sided heart disease as defined by:

    1. PCWP > 15 mmHg
    2. Left ventricular ejection fraction < 40%.

    Note: Subjects with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload (i.e., right ventricular hypertrophy and/or dilatation) will not be excluded.

  5. The subject is receiving > 10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
  6. Current use of any inhaled tobacco/marijuana products or significant history of drug abuse at the time of informed consent.
  7. Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of randomization.
  8. Initiation of pulmonary rehabilitation within 12 weeks prior to the randomization.
  9. In the opinion of the Investigator, the subject has any condition that would interfere with the interpretation of study assessments or has any disease or condition (ie, peripheral vascular disease, musculoskeletal disorder, morbid obesity) that would likely be the primary limit to ambulation (as opposed to PH).
  10. Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization.
  11. Severe concomitant illness limiting life expectancy (< 6 months).
  12. Acute pulmonary embolism within 90 days of randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02630316
Other Study ID Numbers  ICMJE RIN-PH-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party United Therapeutics
Study Sponsor  ICMJE United Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Aaron B Waxman Brigham and Women's Hospital
PRS Account United Therapeutics
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP