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

NCT02579603 | Completed Phase 4 Results

• 2 other identifiers: 1199.2222015-000640-42
• Study Type: interventional
• Target: 105
• Locations: 6 countries
• Sites: 23

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.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With On-treatment Gastrointestinal (GI) AEs (SOC GI Disorders) From 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 Outcomes (2)

• Predose Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline, Weeks 2 and 4

  baseline, prior to intake of study medication on week 2 and week 4

• Predose Plasma Concentrations at Steady State (Cpre,ss) of Pirfenidone

  Prior to intake of study medication on week 2 and week 4

Study Arms (2)

Nintedanib

EXPERIMENTAL

Nintedanib 150 mg bid

Drug: Nintedanib

Nintedanib and Pirfenidone

EXPERIMENTAL

Nintedanib 150 mg bid combined with pirfenidone up to 801 mg tid

Drug: Nintedanib; Drug: Pirfenidone

Interventions

Nintedanib DRUG

Nintedanib 150mg bid

Nintedanib; Nintedanib and Pirfenidone

Pirfenidone DRUG

Also known as: Pirfenidone 801 mg tid

Nintedanib and Pirfenidone

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (23)

Western CT Medical Group, P.C.

Danbury, Connecticut, 06810, United States

Location

Tulane University Hospital and Clinic

New Orleans, Louisiana, 70112, United States

Location

Minnesota Lung Center

Minneapolis, Minnesota, 55407, United States

Location

The Lung Research Center, LLC

Chesterfield, Missouri, 63017, United States

Location

Lowcountry Lung and Crit Care

Charleston, South Carolina, 29406, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-5735, United States

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Concordia Hospital

Winnipeg, Manitoba, R2K 3S8, Canada

Location

HOP Avicenne

Bobigny, 93009, France

Location

HOP de la Cavale Blanche

Brest, 29609, France

Location

HOP Louis Pradel

Bron, 69677, France

Location

HOP Calmette

Lille, 59037, France

Location

HOP Pasteur

Nice, 06001, France

Location

HOP Bichat

Paris, 75018, France

Location

HOP Pontchaillou

Rennes, 35033, France

Location

Klinik Donaustauf

Donaustauf, 93093, Germany

Location

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, 45239, Germany

Location

Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

A.O.U. Policlinico Vittorio Emanuele

Catania, 95124, Italy

Location

Osp. S. Giuseppe Fatebenefratelli

Milan, 20123, Italy

Location

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, 53100, Italy

Location

Sint Antonius Ziekenhuis

Nieuwegein, 3435 CM, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 CE, Netherlands

Location

Related Publications (1)

• Vancheri C, Kreuter M, Richeldi L, Ryerson CJ, Valeyre D, Grutters JC, Wiebe S, Stansen W, Quaresma M, Stowasser S, Wuyts WA; INJOURNEY Trial Investigators. Nintedanib with Add-on Pirfenidone in Idiopathic Pulmonary Fibrosis. Results of the INJOURNEY Trial. Am J Respir Crit Care Med. 2018 Feb 1;197(3):356-363. doi: 10.1164/rccm.201706-1301OC.

  PMID: 28889759 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

nintedanib; pirfenidone

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 19, 2015
• Study Start: October 16, 2015
• Primary Completion: January 3, 2017
• Study Completion: January 31, 2017
• Last Updated: February 13, 2018
• Results First Posted: February 13, 2018

Record last verified: 2018-01

Locations

IT (3); US (6); FR (7); DE (3); NL (2); CA (2)