TY - JOUR
T1 - An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002)
AU - Gotfried, Mark H.
AU - Girod, Carlos E.
AU - Antin-Ozerkis, Danielle
AU - Burgess, Tracy
AU - Strombom, Indiana
AU - Stauffer, John L.
AU - Kirchgaessler, Klaus Uwe
AU - Padilla, Maria L.
N1 - Funding Information:
Additional statistical support was provided by Adefowope Odueyungbo and Philip Hormel of Genentech, Inc. Support for third-party writing assistance, furnished by Benjamin Ricca, Ph.D., of Health Interactions, Inc., was provided by F. Hoffmann-La Roche Ltd.
Funding Information:
This study was originally funded by Marnac, Inc. and completed by InterMune, Inc., which was acquired by F. Hoffmann-La Roche Ltd. in 2014. The journal article’s processing charges were funded by F. Hoffmann-La Roche Ltd. and Genentech, Inc. All authors had full access to all the data in this study and take complete responsibility for the integrity of data and accuracy of the data analysis.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/6
Y1 - 2018/6
N2 - Introduction: PIPF-002 was a phase 2, multicenter, open-label study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) or other types of pulmonary fibrosis (PF). PIPF-002 terminated after pirfenidone became commercially available in the United States. The goal of PIPF-002 was to characterize the long-term safety of pirfenidone in these patients. Methods: Between August 2003 and September 2006, 83 patients (IPF: 81, PF: 2) enrolled. Patients received pirfenidone in three divided doses daily, with the maintenance dose and schedule determined by enrollment group assignment. Treatment continued until patient withdrawal or study termination (2015). Treatment-emergent adverse events (TEAEs) were assessed by descriptive statistics. Results: At baseline, median age was 70 years, mean percent predicted forced vital capacity was 67.7%, 33.7% of patients had cardiac disorders, 51.8% had gastroesophageal reflux disease, and 63.9% were receiving concomitant prednisone. Median pirfenidone dose and exposure duration were 2400 mg/day and 3.0 years, respectively. Cumulative total exposure was 279.7 patient-exposure years (PEY). Most patients (98.8%) reported ≥ 1 TEAE, with an overall incidence rate of 460.5 per 100 PEY. The most frequent TEAEs (incidence rate per 100 PEY) were nausea (23.6), IPF progression (16.1), fatigue (11.8), dyspnea (11.4), upper respiratory tract infection (11.4), and cough (10.7). Serious TEAEs were reported in 49 patients; the most frequent serious TEAEs were IPF progression and pneumonia. The most common reason for discontinuation was TEAEs (35 patients; 12.5 patients per 100 PEY), most frequently IPF progression and nausea. Overall, 21 patients died (7.5 per 100 PEY); 16 deaths were IPF-related. Conclusions: Long-term safety and tolerability of pirfenidone findings in this study were consistent with the known safety profile of pirfenidone; no new safety signals were identified. These data support the continued use of pirfenidone in patients with IPF. Funding: F. Hoffmann-La Roche Ltd./Genentech, Inc. Trial Registration: ClinicalTrials.gov identifier, NCT00080223. Plain Language Summary: Plain language summary available for this article.
AB - Introduction: PIPF-002 was a phase 2, multicenter, open-label study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) or other types of pulmonary fibrosis (PF). PIPF-002 terminated after pirfenidone became commercially available in the United States. The goal of PIPF-002 was to characterize the long-term safety of pirfenidone in these patients. Methods: Between August 2003 and September 2006, 83 patients (IPF: 81, PF: 2) enrolled. Patients received pirfenidone in three divided doses daily, with the maintenance dose and schedule determined by enrollment group assignment. Treatment continued until patient withdrawal or study termination (2015). Treatment-emergent adverse events (TEAEs) were assessed by descriptive statistics. Results: At baseline, median age was 70 years, mean percent predicted forced vital capacity was 67.7%, 33.7% of patients had cardiac disorders, 51.8% had gastroesophageal reflux disease, and 63.9% were receiving concomitant prednisone. Median pirfenidone dose and exposure duration were 2400 mg/day and 3.0 years, respectively. Cumulative total exposure was 279.7 patient-exposure years (PEY). Most patients (98.8%) reported ≥ 1 TEAE, with an overall incidence rate of 460.5 per 100 PEY. The most frequent TEAEs (incidence rate per 100 PEY) were nausea (23.6), IPF progression (16.1), fatigue (11.8), dyspnea (11.4), upper respiratory tract infection (11.4), and cough (10.7). Serious TEAEs were reported in 49 patients; the most frequent serious TEAEs were IPF progression and pneumonia. The most common reason for discontinuation was TEAEs (35 patients; 12.5 patients per 100 PEY), most frequently IPF progression and nausea. Overall, 21 patients died (7.5 per 100 PEY); 16 deaths were IPF-related. Conclusions: Long-term safety and tolerability of pirfenidone findings in this study were consistent with the known safety profile of pirfenidone; no new safety signals were identified. These data support the continued use of pirfenidone in patients with IPF. Funding: F. Hoffmann-La Roche Ltd./Genentech, Inc. Trial Registration: ClinicalTrials.gov identifier, NCT00080223. Plain Language Summary: Plain language summary available for this article.
KW - IPF
KW - Pirfenidone
KW - Safety
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U2 - 10.1007/s41030-018-0053-y
DO - 10.1007/s41030-018-0053-y
M3 - Article
C2 - 32026243
AN - SCOPUS:85070909208
SN - 2364-1754
VL - 4
SP - 59
EP - 71
JO - Pulmonary Therapy
JF - Pulmonary Therapy
IS - 1
ER -