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Respir Med. 2014 Jul;108(7):1023-30. doi: 10.1016/j.rmed.2014.04.011. Epub 2014 Apr 29.

Design of the INPULSIS™ trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis.

Author information

1
National Institute for Health Research Southampton Respiratory Biomedical Research Unit and University of Southampton, University Road, Southampton SO17 1BJ, UK. Electronic address: L.Richeldi@soton.ac.uk.
2
Louis Pradel Hospital, University of Lyon, 28 Avenue du Doyen Lepine, 69677 Bron Cedex, Lyon, France.
3
University of Michigan Health System, 1500 E. Medical Center Drive, 3916 Taubman Center, Ann Arbor, MI 48109-0360, USA.
4
McMaster University, Department of Medicine, Pathology & Molecular Medicine, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.
5
National Hospital Organization Kinki-Chuo Chest Medical Center, Department of Diffuse Lung Diseases and Respiratory Failure, Clinical Research Center, 1180 Nagasone-cho, Kita-Ku, Sakai City, Osaka 591-8555, Japan.
6
University of Washington, Seattle, WA 98105, USA.
7
Tosei General Hospital, Department of Respiratory Medicine and Allergy, 160 Nishioiwake-cho, Seto, Aichi 489-8642, Japan.
8
Royal Brompton and Harefield Hospital NHS Foundation Trust and National Heart and Lung Institute, Imperial College, Sydney Street, London SW3 6NP, UK.
9
Boehringer Ingelheim France S.A.S., 12, rue André Huet - B.P. 292, 51060 Reims Cedex, France.
10
Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216 Ingelheim, Germany.
11
University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94131, USA.

Abstract

BACKGROUND:

Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF). Data from the Phase II TOMORROW study suggested that nintedanib 150 mg twice daily had clinical benefits with an acceptable safety profile.

METHODS:

The INPULSIS™ trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150 mg twice daily with placebo in patients with IPF. Eligible patients were aged ≥40 years with a diagnosis of IPF within 5 years before randomization who had undergone a chest high-resolution computed tomography (HRCT) scan within 1-year before screening, and who had a forced vital capacity (FVC) of ≥50% predicted and a diffusing capacity for carbon monoxide of 30-79% predicted. Participants were randomized 3:2 to receive nintedanib or placebo for 52 weeks. The primary endpoint is the annual rate of decline in FVC. The key secondary endpoints are change from baseline in the total score on the St. George's Respiratory Questionnaire (a measure of health-related quality of life) over 52 weeks and time to first acute exacerbation.

RESULTS:

Enrolment of 1066 patients in 24 countries was completed in September 2012. Results will be reported in the first half of 2014.

CONCLUSION:

The INPULSIS™ trials will determine the efficacy of nintedanib in patients with IPF, including its impact on disease progression as defined by decline in FVC, acute exacerbations and health-related quality of life. In addition, they will characterise the adverse event profile of nintedanib in this patient population.

TRIAL REGISTRATION:

Registered at ClinicalTrials.gov (identifiers: NCT01335464 and NCT01335477).

KEYWORDS:

Clinical trial; Drug therapy; Phase III; Protein kinase inhibitor; Protein tyrosine kinases

PMID:
24834811
DOI:
10.1016/j.rmed.2014.04.011
[Indexed for MEDLINE]
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