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

January 17, 2018 updated by: Boehringer Ingelheim

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)

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.

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

105

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nintedanib
Nintedanib 150 mg bid
Nintedanib 150mg bid
Experimental: Nintedanib and Pirfenidone
Nintedanib 150 mg bid combined with pirfenidone up to 801 mg tid
Nintedanib 150mg bid
Other Names:
  • Pirfenidone 801 mg tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).

Baseline to week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
baseline, prior to intake of study medication on week 2 and week 4
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)
Prior to intake of study medication on week 2 and week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2015

Primary Completion (Actual)

January 3, 2017

Study Completion (Actual)

January 31, 2017

Study Registration Dates

First Submitted

October 16, 2015

First Submitted That Met QC Criteria

October 16, 2015

First Posted (Estimate)

October 19, 2015

Study Record Updates

Last Update Posted (Actual)

February 13, 2018

Last Update Submitted That Met QC Criteria

January 17, 2018

Last Verified

January 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Idiopathic Pulmonary Fibrosis

Clinical Trials on Nintedanib

3
Subscribe