Overview

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

Status:
Completed
Trial end date:
2020-08-22
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hoffmann-La Roche
Treatments:
Pirfenidone
Sildenafil Citrate
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 (<=)40% of predicted value at Screening) and intermediate or high
probability of group 3 pulmonary hypertension (PH)

- Participants receiving pirfenidone for at least 12 weeks, at a dose in the range of
1602 to 2403 mg/day for at least 4 weeks prior to Screening and must not have
experienced either a new or ongoing adverse event of National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI CTCAE) (version 4.03) Grade 2 or higher
and considered by the investigator to be related to pirfenidone, or an interruption of
pirfenidone treatment of greater than (>)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 (<) 0.70 post bronchodilator; SpO2 saturation at rest <92%
with >= 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