A 2-Part, Phase 2 Open-label and Crossover Study of Belumosudil for Treatment of Idiopathic Pulmonary Fibrosis

Inclusion Criteria

A subject had to meet all of the following criteria to be eligible for the study:

• Adult male and postmenopausal/surgically sterilized female subjects at least 18 years of age (if female, was surgically sterilized [i.e., total hysterectomy, or bilateral salpingo-oophorectomy]).
• Able to provide written informed consent before the performance of any study specific procedures.
• IPF diagnosis within 5 years before study entry, proven according to the American Thoracic Society/European Respiratory Society consensus conference criteria, with surgical lung biopsy. In the absence of a surgical lung biopsy, high-resolution computerized tomography (HRCT) consistent with usual interstitial pneumonitis.
• Resting state pulse oximeter oxygen saturation (SpO2) ≥ 88% with or without supplemental oxygen, Forced Vital Capacity % (FVC%) ≥ 50% normal predicted value, and diffusing capcity (in the lung) of carbon monoxide (DLCO) ≥ 30% normal predicted value at baseline.
• Men with partners of childbearing potential willing to use 2 medically acceptable methods of contraception during the trial and for 3 months after the last dose of study drug. Effective birth control includes:
• Intrauterine device plus 1 barrier method
• Stable doses of hormonal contraception for ≥ 3 months (e.g., oral, injectible, implant, transdermal) plus 1 barrier method
• 2 barrier methods. Effective barrier methods were male or female condoms, diaphragms, and spermicides (creams or gels containing a chemical to kill sperm)
• Vasectomy.
• Have adequate bone marrow function:
• Absolute neutrophil count > 1500/mm^3
• Hemoglobin (Hb) > 9.0 g/L
• Platelets > 100,000/mm^3
• Willing to complete all study measurements and assessments in compliance with protocol
• Had either received pirfenidone and/or nintedanib or offered both treatments (with last dose administered at least 1 month before the expected start of study drug dosing). If either or both pirfenidone and nintedanib treatment had not been given, then documentation that the subject was offered both treatments must have been documented.

Exclusion Criteria

A subject who met any of the following criteria was ineligible for the study:

• Interstitial lung disease caused by conditions other than IPF
• Severe concomitant illness limiting life expectancy ( 2.0 * upper limit of normal (ULN)
• Hb 600 mg/day)
• Oral anticoagulants prescribed for IPF
• Treatment with endothelin receptor antagonists within 4 weeks before study entry
• Systemic treatment within 4 weeks before study entry with cyclosporine A or tacrolimus, everolimus, or sirolimus (calcineurin or mammalian target of rapamycin inhibitors)
• Previous exposure to belumosudil or known allergy/sensitivity to belumosudil or any other Rho-associated protein kinase 2 (ROCK2) inhibitor
• Planned treatment or treatment with another investigational drug within 4 weeks before study entry
• Taking a medication with the potential for QTc prolongation
• Taking a drug sensitive substrate of CYP enzymes
• Taking a strong inducer of CYP3A4
• Had consumed an herbal medication (e.g., St. John's Wort) or grapefruit/grapefruit juice within 14 days prior to the Week 1 Day 1 visit