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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02606877
• Date of registration: 16/11/2015
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim
• Public title: A Study to Compare the Amount of Nintedanib and Pirfenidone in the Blood When Nintedanib and Pirfenidone Are Given Separately or in Combination
• Scientific title: Investigation of Drug-drug Interaction Between Nintedanib and Pirfenidone in Patients With IPF (an Open Label, Multiple-dose, Two Group Study)
• Date of first enrolment: April 19, 2016
• Target sample size: 37
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02606877
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United Kingdom

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion 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 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).

Exclusion criteria:

- 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.

- 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)



Age minimum: 40 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: nintedanib

Drug: pirfenidone

Primary Outcome(s)

Pirfenidone-treated, Maximum Measured Concentration of Pirfenidone in Plasma at Steady State (Cmax,ss) [Time Frame: 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 (AUCt,ss) [Time Frame: 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, Area Under the Concentration-time Curve of the Nintedanib in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). [Time Frame: 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). [Time Frame: 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 Outcome(s)

Treatment naïve, Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8) [Time Frame: 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 ID(s)

1199.229

2015-000732-15

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 04/03/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02606877