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Trial record 2 of 7 for:    inhaled treprostinil sodium | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by United Therapeutics
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT02630316
First received: December 11, 2015
Last updated: November 17, 2016
Last verified: November 2016
  Purpose
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 100 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).

Condition Intervention Phase
Pulmonary Hypertension
Interstitial Lung Disease
Combined Pulmonary Fibrosis and Emphysema
Drug: Inhaled Treprostinil
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • Change in 6-minute Walk Distance (6MWD) Measured at Peak Exposure from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Peak 6-minute Walk Distance (6MWD) from Baseline to Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 314
Study Start Date: February 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Matching placebo inhaled using an ultrasonic nebulizer four times daily
Drug: Placebo
Placebo administered four times daily
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
Drug: Inhaled Treprostinil
Inhaled treprostinil (6 mcg/breath) administered four times daily
Other Name: Tyvaso

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject voluntarily gives informed consent to participate in the study.
  2. Males and females aged 18 - 79 years 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 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 (based on computed tomography [CT] imaging and pulmonary function tests [PFTs] performed within six months prior to randomization) of World Health Organization (WHO) Group 3 PH associated with one of the following:

    a. Idiopathic interstitial pneumonia (IIP) including: i. Idiopathic pulmonary fibrosis (IPF) ii. Idiopathic nonspecific interstitial pneumonia iii. Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) iv. Desquamative interstitial pneumonia (DIP) v. Cryptogenic organizing pneumonia (COP) vi. Acute interstitial pneumonitis (AIP) vii. Idiopathic lymphoid interstitial pneumonia viii. Idiopathic pleuroparenchymal fibroelastosis iix. Unclassifiable idiopathic interstitial pneumonia b. Chronic hypersensitivity pneumonitis (CHP) c. Occupational or environmental lung disease (drug or radiation-induced) d. Combined pulmonary fibrosis and emphysema (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) ≥ 4 Wood Units (WU) and
    2. A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) of ≤ 12 mmHg if PVR ≥ 4 WU to < 6.25 WU or ≤ 15 mmHg if PVR ≥ 6.25 WU and
    3. A mean pulmonary arterial pressure (mPAP) of ≥ 30 mmHg
  5. A baseline diffusing capacity of the lungs for carbon monoxide (DLCO) of < 50%
  6. Baseline 6MWD ≥ 100 meters
  7. The subject has not 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 stimulator (sGC) within 60 days of randomization.
  8. Subjects on a chronic medication for underlying lung disease 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.
  9. Subjects on a supportive medication therapy (e.g., anticoagulants, diuretics, oxygen, etc.) must be on a stable and optimized dose for ≥ 30 days prior to randomization. Exceptions are the discontinuation or dose changes of anticoagulants and / or dose change of diuretics.
  10. 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.

Exclusion criteria:

  1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons other than ILD as outlined in inclusion criterion 3. This would include, but is not limited to, the concomitant presence of thromboembolic disease (acute or chronic), untreated or inadequately treated obstructive sleep apnea (OSA), connective tissue disease (including but not limited to systemic sclerosis, scleroderma, or systemic lupus erythematosus [SLE]), sarcoidosis, human immunodeficiency virus (HIV)-1 infection, portopulmonary hypertension, and other conditions of the WHO Group I, II, IV, and V classification.
  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), ERA, PDE-5I, or sGC within 60 days of randomization.
  4. The subject has evidence of clinically significant left-sided heart disease as defined by:

    1. LVEDP or PCWP > 15 mmHg (or > 12 mmHg if PVR ≥ 4 to < 6.25 WU)
    2. Left ventricular ejection fraction < 40% as assessed by either multigated angiogram (MUGA), angiography or echocardiography.

    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. Subjects must not have three or more of the following left ventricular disease/dysfunction risk factors:

    1. Body Mass Index (BMI) ≥ 30 kg/m2
    2. History of Essential Hypertension
    3. Diabetes Mellitus - any type
    4. Historical evidence of significant coronary disease established by any one of the following:

    i. history of myocardial infarction or percutaneous coronary intervention or angiographic, or ii. evidence of coronary artery disease (> 50% stenosis in at least one coronary artery), or iii. positive stress test with imaging, or previous coronary artery bypass graft, or stable angina

  6. The subject is receiving > 10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
  7. Use of any inhaled tobacco/marijuana products or significant history of drug abuse within six months prior to randomization.
  8. Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of randomization.
  9. Initiation of pulmonary rehabilitation within 12 weeks prior to the randomization.
  10. The subject has uncontrolled systemic hypertension as evidenced by systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg.
  11. The subject has any form of congenital heart disease or congenital heart defect (repaired or unrepaired) other than a patent foramen ovale (PFO).
  12. The subject has anemia as defined by a screening hemoglobin value < 9.0 g/dL, active infection, or any other condition that would interfere with the interpretation of study assessments.
  13. The subject has a Body Mass Index ≥ 40 kg/m2.
  14. The subject has any musculoskeletal disorder (i.e., arthritis affecting the lower limbs, recent hip or knee joint replacement, artificial leg), is using a device to assist walking (i.e., cane or walker), or has any other condition that would limit ambulation.
  15. Use of any investigational drug/device, or participation in any investigational study within 30 days prior to randomization.
  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: NCT02630316

Contacts
Contact: Nicole Leedom 919-425-5870 nleedom@unither.com
Contact: Hilary Mauney 919-425-5440 hmauney@unither.com

  Show 44 Study Locations
Sponsors and Collaborators
United Therapeutics
Investigators
Principal Investigator: Aaron Waxman, MD Brigham and Women's Hospital
  More Information

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT02630316     History of Changes
Other Study ID Numbers: RIN-PH-201 
Study First Received: December 11, 2015
Last Updated: November 17, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by United Therapeutics:
Treprostinil
PH
ILD
CPFE
6 Minute Walk Test

Additional relevant MeSH terms:
Treprostinil
Hypertension
Lung Diseases
Hypertension, Pulmonary
Pulmonary Fibrosis
Emphysema
Lung Diseases, Interstitial
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Pathologic Processes
Antihypertensive Agents

ClinicalTrials.gov processed this record on December 06, 2016