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Safety, Tolerability and PK of Nintedanib in Combination With Pirfenidone in IPF

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ClinicalTrials.gov Identifier: NCT02579603
Recruitment Status : Completed
First Posted : October 19, 2015
Results First Posted : February 13, 2018
Last Update Posted : February 13, 2018
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

This is a phase IV, twelve week, open label, randomized, parallel group study to assess safety and tolerability of combined treatment with nintedanib and pirfenidone.

A secondary objective is to assess the exposure based on PK trough concentration values to nintedanib either given alone or in combination with pirfenidone and to assess the exposure of pirfenidone when combined with nintedanib.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: Nintedanib Drug: Pirfenidone Phase 4

Boehringer Ingelheim has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Twelve Week, Open-label, Randomised, Parallel-group Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Oral Nintedanib in Combination With Oral Pirfenidone, Compared to Treatment With Nintedanib Alone, in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Actual Study Start Date : October 16, 2015
Primary Completion Date : January 3, 2017
Study Completion Date : January 31, 2017

Arm Intervention/treatment
Experimental: Nintedanib
Nintedanib 150 mg bid
Drug: Nintedanib
Nintedanib 150mg bid
Experimental: Nintedanib and Pirfenidone
Nintedanib 150 mg bid combined with pirfenidone up to 801 mg tid
Drug: Nintedanib
Nintedanib 150mg bid
Drug: Pirfenidone
Other Name: Pirfenidone 801 mg tid

Primary Outcome Measures :
  1. Percentage of Patients With On-treatment Gastrointestinal (GI) AEs (SOC GI Disorders) From Baseline to Week 12 [ Time Frame: Baseline to week 12 ]

    Percentage of patients with on-treatment gastrointestinal (GI) Adverse events (AEs) (SOC GI disorders) from baseline to week 12.

    On-treatment AEs were defined as AEs with an onset from the first dose of randomised treatment up to the last dose of randomised treatment (inclusive).

Secondary Outcome Measures :
  1. Predose Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline, Weeks 2 and 4 [ Time Frame: baseline, prior to intake of study medication on week 2 and week 4 ]
    Predose plasma concentrations at steady state (Cpre,ss) of nintedanib at baseline (Visit 3), Week 2 (Visit 4) and Week 4 (Visit 5)

  2. Predose Plasma Concentrations at Steady State (Cpre,ss) of Pirfenidone [ Time Frame: Prior to intake of study medication on week 2 and week 4 ]
    Predose plasma concentrations at steady state (Cpre,ss) of pirfenidone at Week 2 (Visit 4) and Week 4 (Visit 5)

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Written informed consent consistent with ICH-GCP(The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use- Good clinical practice) and local laws, signed prior to any study procedures being performed (including any required washout)
  • Male or female patients aged greater than or equal to 40 years at visit 1
  • Idiopathic Pulmonary Fibrosis (IPF) diagnosis, based upon the ATS (American Thoracic Society)/ERS (European Respiratory Society)/JRS (Japanese Respiratory Society)/ALAT (Latin American Thoracic Association) 2011 guideline and confirmed by the investigator based on chest high resolution computed tomography (HRCT) scan performed within 12 months of visit 1
  • FVC (Forced vital capacity) greater than or equal to 50% of predicted normal at visit 1

Exclusion criteria:

  • ALT (Alanine transaminase), AST (Aspartate aminotransferase)> 1.5 fold upper limit of normal (ULN) at visit 1
  • Total bilirubin > 1.5 fold ULN at visit 1
  • Relevant airways obstruction (i.e. pre-bronchodilator FEV1 (Forced Expiratory Volume in one second)/FVC <0.7) at visit 1
  • History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of visit 1
  • Bleeding Risk: Known genetic predisposition to bleeding, Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, dabigatran, heparin, hirudin etc) or high dose antiplatelet therapy, History of haemorrhagic central nervous system event within 12 months prior to visit 1, History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1, International normalised ratio (INR) > 2 at visit 1, Prothrombin time and partial thromboplastin time (PTT) > 150% of institutional ULN at visit 1
  • Planned major surgery during the trial participation, including lung transplantation,major abdominal or major intestinal surgery.
  • History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1
  • Severe renal impairment (Creatinine clearance <30 mL/min calculated by Cockcroft-Gault formula at visit 1) or end-stage renal disease requiring dialysis
  • Treatment with NAC (n-acetylcysteine), prednisone >15 mg daily or >30 mg every 2 days OR equivalent dose of other oral corticosteroids and/or fluvoxamine within 2 weeks of visit 2
  • Treatment with azathioprine, cyclophosphamide, cyclosporine as well as any other investigational drug within 8 weeks of visit 2
  • Previous treatment with pirfenidone
  • Permanent discontinuation of nintedanib in the past due to Adverse Events considered drug-related
  • Known hypersensitivity to nintedanib, pirfenidone, peanut or soya or to any of the excipients
  • A disease or condition which in the opinion of the investigator may interfere with testing procedures or put the patient at risk when participating in this trial
  • Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial
  • Women of childbearing potential not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly5 for 28 days prior to and 3 months after nintedanib administration
  • Patients not able to understand and follow study procedures including completion of self administered questionnaires without help
  • Patients who require dose reduction and/or temporary interruption during the run-in period with nintedanib 150 mg bid
  • Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02579603

United States, Connecticut
Western CT Medical Group, P.C.
Danbury, Connecticut, United States, 06810
United States, Louisiana
Tulane University Hospital and Clinic
New Orleans, Louisiana, United States, 70112
United States, Minnesota
Minnesota Lung Center
Minneapolis, Minnesota, United States, 55407
United States, Missouri
The Lung Research Center, LLC
Chesterfield, Missouri, United States, 63017
United States, South Carolina
Lowcountry Lung and Crit Care
Charleston, South Carolina, United States, 29406
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-5735
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Manitoba
Concordia Hospital
Winnipeg, Manitoba, Canada, R2K 3S8
HOP Avicenne
Bobigny, France, 93009
HOP de la Cavale Blanche
Brest, France, 29609
HOP Louis Pradel
Bron cedex, France, 69677
HOP Calmette
Lille, France, 59037
HOP Pasteur
Nice, France, 06001
HOP Bichat
Paris, France, 75018
HOP Pontchaillou
Rennes, France, 35033
Klinik Donaustauf
Donaustauf, Germany, 93093
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
Essen, Germany, 45239
Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
Heidelberg, Germany, 69126
A.O.U. Policlinico Vittorio Emanuele
Catania, Italy, 95124
Osp. S. Giuseppe Fatebenefratelli
Milano, Italy, 20123
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, Italy, 53100
Sint Antonius Ziekenhuis
Nieuwegein, Netherlands, 3435 CM
Erasmus Medisch Centrum
Rotterdam, Netherlands, 3015 CE
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02579603     History of Changes
Other Study ID Numbers: 1199.222
2015-000640-42 ( EudraCT Number )
First Posted: October 19, 2015    Key Record Dates
Results First Posted: February 13, 2018
Last Update Posted: February 13, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents