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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02579603
First Posted: October 19, 2015
Last Update Posted: May 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
  Purpose

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 Intervention 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
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The primary endpoint is the percentage of patients with on-treatment gastrointestinal (GI) AEs (SOC GI disorders) from baseline to week 12 [ Time Frame: 12 weeks ]

Secondary Outcome Measures:
  • Pre-dose plasma concentrations at steady state (Cpre,ss) of nintedanib at baseline, weeks 2 and 4 [ Time Frame: baseline, week 2 and week 4 ]
  • Pre-dose plasma concentrations at steady state (Cpre,ss) of pirfenidone at weeks 2 and 4. [ Time Frame: week 2 and week 4 ]

Enrollment: 105
Actual Study Start Date: October 16, 2015
Study Completion Date: January 31, 2017
Primary Completion Date: January 3, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion criteria:

  • Written informed consent consistent with ICH-GCP 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/ERS/JRS/ALAT 2011 guideline and confirmed by the investigator based on chest high resolution computed tomography (HRCT) scan performed within 12 months of visit 1
  • FVC greater than or equal to 50% of predicted normal at visit 1

Exclusion criteria:

  • ALT, AST > 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/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, 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 AEs 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 selfadministered 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)
  Contacts and Locations
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


  Show 28 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02579603     History of Changes
Other Study ID Numbers: 1199.222
2015-000640-42 ( EudraCT Number: EudraCT )
First Submitted: October 16, 2015
First Posted: October 19, 2015
Last Update Posted: May 18, 2017
Last Verified: May 2017

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