An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002)
Abstract 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 wa...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2018-06-01
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| Series: | Pulmonary Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s41030-018-0053-y |
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| author | Mark H. Gotfried Carlos E. Girod Danielle Antin-Ozerkis Tracy Burgess Indiana Strombom John L. Stauffer Klaus-Uwe Kirchgaessler Maria L. Padilla |
| author_facet | Mark H. Gotfried Carlos E. Girod Danielle Antin-Ozerkis Tracy Burgess Indiana Strombom John L. Stauffer Klaus-Uwe Kirchgaessler Maria L. Padilla |
| author_sort | Mark H. Gotfried |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T12:36:52Z |
| format | Article |
| id | doaj.art-08433ccedbe14538acc3964d89086de2 |
| institution | Directory Open Access Journal |
| issn | 2364-1754 2364-1746 |
| language | English |
| last_indexed | 2024-04-24T12:36:52Z |
| publishDate | 2018-06-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Pulmonary Therapy |
| spelling | doaj.art-08433ccedbe14538acc3964d89086de22024-04-07T11:26:28ZengAdis, Springer HealthcarePulmonary Therapy2364-17542364-17462018-06-0141597110.1007/s41030-018-0053-yAn Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002)Mark H. Gotfried0Carlos E. Girod1Danielle Antin-Ozerkis2Tracy Burgess3Indiana Strombom4John L. Stauffer5Klaus-Uwe Kirchgaessler6Maria L. Padilla7Pulmonary AssociatesThe University of Texas Southwestern Medical CenterYale School of MedicineGenentech, Inc.Genentech, Inc.Genentech, Inc.F. Hoffmann-La Roche Ltd.Icahn School of Medicine at Mount SinaiAbstract 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.https://doi.org/10.1007/s41030-018-0053-yIPFPirfenidoneSafety |
| spellingShingle | Mark H. Gotfried Carlos E. Girod Danielle Antin-Ozerkis Tracy Burgess Indiana Strombom John L. Stauffer Klaus-Uwe Kirchgaessler Maria L. Padilla An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002) Pulmonary Therapy IPF Pirfenidone Safety |
| title | An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002) |
| title_full | An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002) |
| title_fullStr | An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002) |
| title_full_unstemmed | An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002) |
| title_short | An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002) |
| title_sort | open label phase ii study of the safety of pirfenidone in patients with idiopathic pulmonary fibrosis pipf 002 |
| topic | IPF Pirfenidone Safety |
| url | https://doi.org/10.1007/s41030-018-0053-y |
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