Idiopathic Pulmonary FibrosisPhase 4NCT02579603
Safety, Tolerability and PK of Nintedanib in Combination With Pirfenidone in IPF
A Phase 4 study testing Nintedanib and Pirfenidone in people with Idiopathic Pulmonary Fibrosis, run by Boehringer Ingelheim at 23 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- Nintedanib and Pirfenidone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 16 Oct 2015to 31 Jan 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 20Show fewer
- 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)
Trial locations and contacts
23 sites in 6 countries.
23 sites in 6 countries
France7 sites
HOP Avicenne
Bobigny, 93009
HOP de la Cavale Blanche
Brest, 29609
HOP Louis Pradel
Bron, 69677
HOP Calmette
Lille, 59037
HOP Pasteur
Nice, 06001
HOP Bichat
Paris, 75018
HOP Pontchaillou
Rennes, 35033
United States6 sites
Lowcountry Lung and Crit Care
Charleston, South Carolina, 29406
The Lung Research Center, LLC
Chesterfield, Missouri, 63017
Western CT Medical Group, P.C.
Danbury, Connecticut, 06810
Minnesota Lung Center
Minneapolis, Minnesota, 55407
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-5735
Tulane University Hospital and Clinic
New Orleans, Louisiana, 70112
Germany3 sites
Klinik Donaustauf
Donaustauf, 93093
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
Essen, 45239
Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
Heidelberg, 69126
Italy3 sites
A.O.U. Policlinico Vittorio Emanuele
Catania, 95124
Osp. S. Giuseppe Fatebenefratelli
Milan, 20123
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, 53100
Canada2 sites
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Concordia Hospital
Winnipeg, Manitoba, R2K 3S8
Netherlands2 sites
Sint Antonius Ziekenhuis
Nieuwegein, 3435 CM
Erasmus Medisch Centrum
Rotterdam, 3015 CE
About this study
Official title: 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.
- Conditions
- Idiopathic Pulmonary Fibrosis
- Being tested
- Nintedanib, Pirfenidone
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NintedanibDrug
Nintedanib 150mg bid
PirfenidoneDrug
Also called Pirfenidone 801 mg tid
| Study group | Role | What they receive |
|---|---|---|
| Nintedanib | Experimental | Nintedanib 150 mg bid Receives: Drug: Nintedanib |
| Nintedanib and Pirfenidone | Experimental | Nintedanib 150 mg bid combined with pirfenidone up to 801 mg tid Receives: Drug: Nintedanib; Drug: Pirfenidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline to week 12
Secondary outcomes (2)
Predose Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline, Weeks 2 and 4
Predose plasma concentrations at steady state (Cpre,ss) of nintedanib at baseline (Visit 3), Week 2 (Visit 4) and Week 4 (Visit 5)
Measured: baseline, prior to intake of study medication on week 2 and week 4
Predose Plasma Concentrations at Steady State (Cpre,ss) of Pirfenidone
Predose plasma concentrations at steady state (Cpre,ss) of pirfenidone at Week 2 (Visit 4) and Week 4 (Visit 5)
Measured: Prior to intake of study medication on week 2 and week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2015 (estimated)
- Study start16 Oct 2015
- Primary completion3 Jan 2017
- Study completion31 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02579603
- Sponsor's protocol ID
- 1199.222
- Other IDs
- 2015-000640-42, 2015
- Status last verified
- Jan 2018
- First submitted
- 16 Oct 2015
- Last updated
- 13 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Expanded access
- Available
Publications
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.
PubMed 28889759
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02579603
- Acronym / sponsor ID
- 1199.222
- Conditions
- Idiopathic Pulmonary Fibrosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 16 Oct 2015 (actual)
- Primary completion
- 3 Jan 2017 (actual)
- Study completion
- 31 Jan 2017 (actual)
- First posted
- 19 Oct 2015 (estimated)
- Results
- Posted 13 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nintedanib | Experimental | Drug: NintedanibNintedanib 150 mg bid |
| Nintedanib and Pirfenidone | Experimental | Drug: Nintedanib, Drug: PirfenidoneNintedanib 150 mg bid combined with pirfenidone up to 801 mg tid |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NintedanibNintedanib 150mg bid | Drug | Nintedanib, Nintedanib and Pirfenidone |
| PirfenidoneAlso: Pirfenidone 801 mg tid | Drug | Nintedanib and Pirfenidone |
Primary outcome
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).
2 secondary outcomes
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 Pirfenidone
Time frame: Prior to intake of study medication on week 2 and week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28889759Vancheri 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
23 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nintedanib and Pirfenidone in people with Idiopathic Pulmonary Fibrosis, run by Boehringer Ingelheim at 23 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in France, United States, Germany, Italy, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With On-treatment Gastrointestinal (GI) AEs (SOC GI Disorders) From Baseline to Week 12 (time frame: Baseline to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02579603, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2018.