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

Conditions: Idiopathic Pulmonary Fibrosis

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 (\<=)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 (\ = 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