Change in 6MWD measured at peak exposure from baseline to week 16 (between 10 and 60 minutes after most recent dose)
STUDY OVERVIEW
INCREASE was designed to assess the efficacy and safety of TYVASO in patients with PH-ILD1
The INCREASE trial was a 16-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study of 326 patients1-3*
*The starting dose was 3 breaths, 4x daily (during waking hours). Dose escalations (1 breath, 4x daily) could occur up to every 3 days, with a target maintenance dose of 9 breaths, 4x daily, and a maximum of 12 breaths, as clinically tolerated.1,2
TYVASO was evaluated across multiple clinical endpoints
Primary Endpoint2
Secondary Endpoints1,4
Change in NT-proBNP from baseline to week 16
Time to first clinical worsening event—from time of randomization until study discontinuation (1 of the following criteria met):
- Hospitalization due to a cardiopulmonary indication
- Decrease in 6MWD >15% from baseline directly related to disease under study at 2 consecutive visits and ≥24 hours apart
- Death (all causes)
- Lung transplantation
Change in peak 6MWD at week 12
Change in trough 6MWD at week 15
- ≥4 hours after the most recent study drug dose and ≥24 hours prior to week 16 6MWD
Select Safety Endpoints4†
AEs
Oxygenation:
- Pulse oximetry (SpO2)
- Supplemental oxygen requirement (L/min)
PFTs‡:
- Forced vital capacity (FVC)
- Forced expiratory volume in 1 second (FEV1)
- Total lung capacity (TLC)
- Lung diffusion capacity (DLCO)
Exacerbations of underlying lung disease§
Based on a concern that treating WHO Group 3 pulmonary hypertension with pulmonary vasodilators could worsen V/Q matching in patients, PFTs (including FVC) and exacerbations were included as safety endpoints due to the potential risk of V/Q mismatch.5
Key Inclusion Criteria4
Key Exclusion Criteria4
Baseline characteristics of the INCREASE study population (N=326)1,2,4
| Time since PH-ILD diagnosis | 6.5 months (mean) |
|---|---|
| Supplemental oxygen | 71.5% |
|
Chronic medication for underlying lung disease¶ |
|
| 6MWD | 259.6 m (mean) |
| NT-proBNP | 503.9 pg/mL (median) |
| FVC (% predicted) | TYVASO group: 62.5% (mean) Placebo group: 63.8% (mean) |
| DLCO (% predicted) | TYVASO group: 30.0% (mean) Placebo group: 28.1% (mean) |
†Additional safety endpoints included clinical laboratory parameters, vital signs, electrocardiograms, and hospitalizations due to a cardiopulmonary indication.4
‡PFTs were prespecified as safety assessments; however, based on study results, exploratory post hoc efficacy analyses were conducted.1,3
§
An acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality determined by the investigator.1
¶
Patients taking a chronic medication for underlying lung disease represented 22.7% of the total study population.1
6MWD=6-minute walk distance; AE=adverse event; CHP=chronic hypersensitivity pneumonitis; CPFE=combined pulmonary fibrosis and emphysema; CT=computed tomography; CTD=connective tissue disease; DLCO=diffusing capacity of the lung for carbon monoxide; IIP=idiopathic interstitial pneumonia; ILD=interstitial lung disease; IPF=idiopathic pulmonary fibrosis; LVEF=left ventricular ejection fraction; NT-proBNP=N-terminal pro−B-type natriuretic peptide; PAH=pulmonary arterial hypertension; PFT=pulmonary function test; PH=pulmonary hypertension; SpO2=saturation of peripheral capillary oxygenation; V/Q=ventilation/perfusion; WHO=World Health Organization; WU=Wood units.
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