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A Study to Compare the Amount of Nintedanib and Pirfenidone in the Blood When Nintedanib and Pirfenidone Are Given Separately or in Combination

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ClinicalTrials.gov Identifier: NCT02606877
Recruitment Status : Completed
First Posted : November 17, 2015
Last Update Posted : December 18, 2017
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
The primary objective of this study is to investigate the effect of steady state pirfenidone on the pharmacokinetics of nintedanib and its metabolites following oral administration of 2403 mg/day pirfenidone and to investigate the effect of steady state nintedanib on the pharmacokinetics of pirfenidone at steady state following oral administration of 150 mg bid nintedanib. There will be two cohorts of patients; the first one will consist of patients not treated with pirfenidone or nintedanib, while the second one will consist of patients on pirfenidone treatment.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: nintedanib Drug: pirfenidone Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigation of Drug-drug Interaction Between Nintedanib and Pirfenidone in Patients With IPF (an Open Label, Multiple-dose, Two Group Study)
Actual Study Start Date : April 19, 2016
Actual Primary Completion Date : March 22, 2017
Actual Study Completion Date : March 22, 2017


Arm Intervention/treatment
Experimental: Group 1
Treatment naïve to pirfenidone
Drug: nintedanib
Drug: pirfenidone
Experimental: Group 2
Treatment before with pirfenidone
Drug: nintedanib
Drug: pirfenidone



Primary Outcome Measures :
  1. Group 2 - area under the concentration-time curve of pirfenidone in plasma over a dosing interval [ Time Frame: 16 days ]
  2. Group 2 - maximum measured concentration of pirfenidone in plasma at steady state [ Time Frame: 16 days ]
  3. Group 1 - Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 to the last measured time point [ Time Frame: 24 days ]
  4. Group 1 - maximum measured concentration of Nintedanib in plasma after single dose administration [ Time Frame: 24days ]

Secondary Outcome Measures :
  1. Group 1 - area under the concentration-time curve of nintedanib in plasma over the time interval from 0 to infinity [ Time Frame: 24 days ]


Information from the National Library of Medicine

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

Inclusion criteria:

Any patients diagnosed with IPF and who comply with eligibility requirements may qualify for participation in the trial.

  • 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 >=40 years at Visit 1
  • IPF diagnosis, based upon the ATS/ERS/JRS/ALAT 2011 guideline and chest high-resolution computed tomography (HRCT) scan.
  • FVC >=50% of predicted normal at Visit 1
  • DLCO (corrected for Hb [visit 1]): 30%-79% predicted of normal at visit 2. (test can be performed at visits 1 or 2, or during the screening period)
  • Currently treated with pirfenidone at full dose (this is only for patients going into Group 2).

Exclusion criteria:

  • ALT, AST >1.5 fold upper limit of normal (ULN) at visit 1.
  • Total bilirubin >1.5 fold ULN at visit 1.
  • Underlying chronic liver disease (Child Pugh A, B, or C hepatic impairment)
  • 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 (CNS) 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 (PT) 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 n-acetylcysteine, prednisone >15 mg daily or >30 mg every 2 days OR equivalent dose of other oral corticosteroids 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 in the past three months prior to Visit 2 (Group 1 only).
  • Previous treatment with nintedanib in the past 14 days prior to Visit 2.
  • Permanent discontinuation of nintedanib or pirfenidone in the past due to adverse events considered drug-related.
  • Known hypersensitivity to nintedanib, pirfenidone or their excipients; or to peanut or soya.
  • 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 using highly effective methods of birth control per ICH M3, note 3, highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner. Barrier contraceptives (e.g. male condom or diaphragm) are acceptable if used in combination with spermicides (e.g. foam, gel). Contraception must be used for 28 days prior to and 3 months after nintedanib and pirfenidone administration.
  • Patients not able to understand and follow study procedures including completion of diaries without help.
  • Current smoker (vaping and e-cigarettes are acceptable)

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): NCT02606877


Locations
United Kingdom
Southmead Hospital
Bristol, United Kingdom, BS10 5NB
Papworth Hospital
Cambridge, United Kingdom, CB23 3RE
Glenfield Hospital
Leicester, United Kingdom, LE3 9QP
University College London Hospital
London, United Kingdom, NW1 2PG
Guy's Hospital
London, United Kingdom, SE1 9RT
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Wythenshawe Hospital
Manchester, United Kingdom, M23 9LT
Churchill Hospital
Oxford, United Kingdom, OX3 7LE
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02606877     History of Changes
Other Study ID Numbers: 1199.229
2015-000732-15 ( EudraCT Number )
First Posted: November 17, 2015    Key Record Dates
Last Update Posted: December 18, 2017
Last Verified: December 2017

Additional relevant MeSH terms:
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
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