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


CONCLUSIONS
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.


BACKGROUND
Registered at ClinicalTrials.gov (identifiers: NCT01335464 and NCT01335477).
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.
Luca
L
Richeldi
Louis Pradel Hospital, University of Lyon, 28 Avenue du Doyen Lepine, 69677 Bron Cedex, Lyon, France.
Vincent
V
Cottin
University of Michigan Health System, 1500 E. Medical Center Drive, 3916 Taubman Center, Ann Arbor, MI 48109-0360, USA.
Kevin R
KR
Flaherty
McMaster University, Department of Medicine, Pathology & Molecular Medicine, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.
Martin
M
Kolb
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.
Yoshikazu
Y
Inoue
University of Washington, Seattle, WA 98105, USA.
Ganesh
G
Raghu
Tosei General Hospital, Department of Respiratory Medicine and Allergy, 160 Nishioiwake-cho, Seto, Aichi 489-8642, Japan.
Hiroyuki
H
Taniguchi
Royal Brompton and Harefield Hospital NHS Foundation Trust and National Heart and Lung Institute, Imperial College, Sydney Street, London SW3 6NP, UK.
David M
DM
Hansell
Royal Brompton and Harefield Hospital NHS Foundation Trust and National Heart and Lung Institute, Imperial College, Sydney Street, London SW3 6NP, UK.
Andrew G
AG
Nicholson
Boehringer Ingelheim France S.A.S., 12, rue André Huet - B.P. 292, 51060 Reims Cedex, France.
Florence
F
Le Maulf
Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216 Ingelheim, Germany.
Susanne
S
Stowasser
University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94131, USA.
Harold R
HR
Collard
D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015337:Multicenter Studies as Topic; D018579:Patient Selection; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D007211:Indoles; D047428:Protein Kinase Inhibitors; C530716:nintedanib
Clinical trial; Drug therapy; Phase III; Protein kinase inhibitor; Protein tyrosine kinases