Phase 2
N=177
Efficacy, Safety, and Tolerability Study of Pirfenidone in Combination With Sildenafil in Participants With Advanced Idiopathic Pulmonary Fibrosis (IPF) and Intermediate or High Probability of Group 3 Pulmonary Hypertension
Idiopathic Pulmonary Fibrosis
Bottom Line
View on ClinicalTrials.gov: NCT02951429 ↗Enrolled (actual)
177
Serious AEs
61.6%
Results posted
Nov 2020
Primary outcome: Primary: Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause — 72.7; 69.7 Percentage of Participants — p=0.6527
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Pirfenidone (Drug); Placebo (Drug); Sildenafil (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Sep 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause |
72.7; 69.7 | 0.6527 |
| SECONDARY Time to First Occurrence of Disease Progression |
26.00; 25.43 | 0.7568 |
| SECONDARY Time to Multiple Occurrence of Disease Progression Events |
20.57; 13.29 | 0.3760 |
| SECONDARY Percentage of Participants With Decline From Baseline in 6-minute Walking Distance (6MWD) of >= 15% |
53.4; 50.6 | 0.7046 |
| SECONDARY Time to First Occurrence of Relevant ≥15% Decline From Baseline in 6-minute Walking Distance (6MWD) |
39.00; 38.71 | 0.7550 |
| SECONDARY Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52 |
54.29; NA | 0.9174 |
| SECONDARY Time to All-Cause Non-Elective Hospitalization |
47.57; 49.86 | 0.7748 |
| SECONDARY Time to Death From Any Cause |
NA; NA | 0.4258 |
| SECONDARY Percentage of Participants With Lung Transplantation |
10.2; 6.7 | — |
| SECONDARY Time to Respiratory-Related Death |
NA; NA | 0.3161 |
| SECONDARY Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Peak Tricuspid Regurgitation Velocity |
-0.014; 0.103 | — |
| SECONDARY Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Pulmonary Artery Pressure (PAPs) |
2.0; 3.6 | — |
| SECONDARY Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Tricuspid Annular Plane Systolic Excursion (TAPSE) |
-0.204; -0.146 | — |
| SECONDARY Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Right Ventricle Basal Diameter |
0.462; 0.095 | — |
| SECONDARY Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Inferior Vena Cava Diameter |
-0.05; -0.09 | — |
| SECONDARY Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Left Ventricular Ejection Fraction (LVEF) |
1.22; -0.85 | — |
| SECONDARY Change From Baseline to Week 52 in Carbon Monoxide Diffusing Capacity/ Pulmonary Diffusing Capacity (DLCO) |
-2.918; -2.440 | — |
| SECONDARY Change From Baseline to Week 52 in Forced Vital Capacity (FVC) |
-2.761; -1.616 | — |
| SECONDARY Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52 |
19.3; 13.5; 33.0; 24.7; 3.4; 1.1 | — |
| SECONDARY Change From Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Level (pg/mL) at Week 52 |
110.1; 605.9 | 0.5646 |
| SECONDARY St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52 |
6.149; 11.437; 2.498; 8.261; 3.997; 10.871 | 0.5255 |
| SECONDARY University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Changes From Baseline at Week 52 |
12.5; 18.8 | 0.4263 |
| SECONDARY Change From Baseline in Distance Walked, 6-minute Walking Distance (6MWD) Test at Week 52 |
-52.9; -40.8 | — |
| SECONDARY Change From Baseline in Oxygen Requirements, 6-minute Walking Distance (6MWD) Test at Week 52 |
0.6; 0.6 | — |
| SECONDARY Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters at Week 52 |
-0.5; -0.8; -3.4; 0.3; 0.5; -2.3 | — |
| SECONDARY Percentage of Participants With Adverse Events |
98.9; 93.3 | — |
| SECONDARY Borg Scale Result at the End of the Test at Week 52 |
0.9; 0.7 | — |
Summary
This Phase IIb, randomized, placebo-controlled, multicenter, international study will evaluate the efficacy, safety, and tolerability of sildenafil or placebo added to pirfenidone (Esbriet) treatment in participants with advanced IPF and intermediate or high probability of Group 3 pulmonary hypertension (PH) who are on a stable dose of pirfenidone with demonstrated tolerability. Participants will be randomized to receive 1 year of treatment with either oral sildenafil or matching placebo while continuing to take pirfenidone.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of IPF for at least 3 months prior to Screening
- Confirmation of IPF diagnosis by the investigator in accordance with the 2011 international consensus guidelines at screening
- Advanced IPF (defined as a measurable carbon monoxide diffusing capacity [DLCO] less than or equal to ( )7 days for any reason
- WHO Functional Class II or III at Screening
- 6MWD of 100 to 450 meters at screening
- Women of childbearing potential and for men who are not surgically sterile agreement to remain abstinent or use of contraceptive measures
Exclusion Criteria
- History of any of the following types of PH: Group 1 (PAH); Group 1 (pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis); Group 2 (left-heart disease); Group 3 (due to conditions other than interstitial lung disease, including chronic obstructive pulmonary disease [COPD], sleep-disordered breathing, alveolar hypoventilation, high altitude, or developmental abnormalities); Group 4 (chronic thromboembolic pulmonary hypertension); Group 5 (other disorders)
- History of clinically significant cardiac disease
- History of coexistent and clinically significant COPD, bronchiectasis, asthma, inadequately treated sleep-disordered breathing, or any clinically significant pulmonary diseases or disorders other than IPF or PH secondary to IPF
- History of use of drugs and toxins known to cause PAH, including aminorex, fenfluramine, dexenfluramine, and amphetamines
- FEV1/FVC ratio less than ( = 6 liters (L) of supplemental oxygen at Screening
- Extent of emphysema greater than the extent of fibrotic changes (honeycombing and reticular changes) on any previous high-resolution computed tomography (HRCT) scan, in the opinion of the Investigator
- Smoked tobacco within 3 months prior to screening or is unwilling to avoid tobacco products (cigarettes, pipe, cigars) throughout the study
- Illicit drug or significant alcohol abuse
- Electrocardiogram (ECG) with a heart-rate corrected QT interval (corrected using Fridericia's formula [QTcF]) >=500 milliseconds (ms) at screening, or a family or personal history of long QT syndrome
- Exclusion criteria based on pirfenidone reference safety information: 1. participants with a history of angioedema due to pirfenidone; 2. concomitant use of fluvoxamine
- Exclusion criteria based on sildenafil reference safety information: 1. co-administration with nitric oxide donors or organic nitrates, phosphodiesterase-5 (PDE5) inhibitors, guanylate cyclase stimulators, and most potent of the Cytochrome P450 3A4 (CYP3A4) inhibitors; 2. loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION); 3. use of an alpha-blocker; 4. participants with bleeding disorders or active peptic ulceration; 5. known hereditary degenerative retinal disorders such as retinitis pigmentosa; 6. galactose intolerance
Data sourced from ClinicalTrials.gov (NCT02951429). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.