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

NCT02606877 | Completed Phase 4 Results

• 2 other identifiers: 1199.2292015-000732-15
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 9

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.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (4)

• Treatment naïve, Area Under the Concentration-time Curve of the Nintedanib in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz).

  AUC0-tz , area under the concentration-time curve of nintedanib in plasma over the time interval from 0 to the last quantifiable concentration. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error.

  Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose.

• Treatment naïve, Maximum Measured Concentration of Nintedanib in Plasma After Single Dose Administration (Cmax).

  Cmax, maximum measured concentration of nintedanib in plasma. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error.

  Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose.

• Pirfenidone-treated, Area Under the Concentration-time Curve of Pirfenidone in Plasma Over a Dosing Interval at Steady State (AUCτ,ss)

  AUCτ,ss, area under the concentration-time curve of pirfenidone in plasma over a dosing interval at steady state. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error.

  Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose.

• Pirfenidone-treated, Maximum Measured Concentration of Pirfenidone in Plasma at Steady State (Cmax,ss)

  Cmax,ss, maximum measured concentration of pirfenidone in plasma at steady state. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error.

  Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose.

Secondary Outcomes (1)

• Treatment naïve, Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

  Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose.

Study Arms (2)

Treatment naïve

EXPERIMENTAL

Treatment naïve to pirfenidone

Drug: nintedanib; Drug: pirfenidone

Pirfenidone-treated

EXPERIMENTAL

Treatment before with pirfenidone

Drug: nintedanib; Drug: pirfenidone

Interventions

nintedanib DRUG

Pirfenidone-treated; Treatment naïve

pirfenidone DRUG

Pirfenidone-treated; Treatment naïve

Eligibility Criteria

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

You may qualify if:

• Any patients diagnosed with IPF and who comply with eligibility requirements may qualify for participation in the trial.
• Written informed consent consistent with International Conference on Harmonisation - Good Clinical Practice (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 American Thoracic Society (ATS)/European Respiratory Society(ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 2011 guideline and chest high-resolution computed tomography (HRCT) scan.
• Force Vital Capacity (FVC) \>=50% of predicted normal at Visit 1
• Diffusing capacity of the Lung for Carbon monoxide (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).

You may not qualify if:

• Alanine transaminase (ALT), Aspartate aminotransferase (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 Forced Expiratory Volume in 1 second (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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (9)

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

Location

Papworth Hospital

Cambridge, CB23 3RE, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2015
• First Posted: November 17, 2015
• Study Start: April 19, 2016
• Primary Completion: March 22, 2017
• Study Completion: March 22, 2017
• Last Updated: March 4, 2019
• Results First Posted: March 4, 2019

Record last verified: 2018-11

Locations

GB (9)