Idiopathic Pulmonary FibrosisPhase 4NCT02598193
Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF)
A Phase 4 study testing Nintedanib and Pirfenidone in people with Idiopathic Pulmonary Fibrosis, run by Hoffmann-La Roche at 38 sites in 8 countries.
Trial summary
This clinical study will evaluate the safety and tolerability of combination treatment of nintedanib and pirfenidone in participants with IPF. Eligible participants must have received pirfenidone for at least 16 weeks on a stable dose. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- 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
- 89 participants
- Where
- 38 sitesin 8 countries
- Study dates
- 14 Jan 2016to 16 May 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants who are on pirfenidone for at least 16 weeks and on a stable dose (defined as 1602-2403 mg/day) for at least 28 days at the start of Screening; the dose must be expected to remain in that range throughout the study
- Documented diagnosis of IPF, per the Investigator per using the criteria of the 2011 American Thoracic Society / European Respiratory Society / Japanese Respiratory Society / Latin American Thoracic Association guidelines
- Participants with percent predicted forced vital capacity (FVC) more than or equal to (>=) 50 percent (%) and percent predicted carbon monoxide diffusing capacity (DLco) >=30% at Screening
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1% per year, during the treatment period and for at least 3 months after the final Follow-up Visit
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least 4 months after the final Follow-up Visit
Who cannot join
- Participants with clinical evidence of active infection
- Participant with any new or ongoing moderate or severe adverse reaction considered by the Investigator to be related to pirfenidone, or an pirfenidone treatment interruption in the 28 days before the start of Screening
- Any condition that is likely to result in death in the 12 months after the start of Screening
- Lung transplantation anticipated or any planned significant surgical intervention
- Known hypersensitivity to the active substance or any excipient of either pirfenidone or nintedanib
- Mild (Child Pugh A), moderate (Child Pugh B), or severe (Child Pugh C) hepatic and/or severe renal impairment
Show all 12Show fewer
- History of gastrointestinal (GI) tract perforation, unstable or deteriorating cardiac or pulmonary disease (other than IPF), long QT syndrome, alcohol or substance abuse in the 2 years before the start of screening, use of any tobacco product in the 12 weeks before the start of screening
- Bleeding risk
- Use of Cytochrome P450 (CYP) 1A2 (CYP1A2) inhibitors (for example, fluvoxamine, enoxacin) and/or use of inhibitors of P-glycoprotein (for example, ketoconazole, erythromycin) or CYP3A4 (for example, ketoconazole, erythromycin) or their inducers (for example, rifampicin, carbamazepine, phenytoin, St John's wort) in the 28 days before the start of Screening
- Pregnancy or lactation
- Hypersensitivity to peanuts and/or soy
- Use of pirfenidone and/or nintedanib in a clinical study protocol in the 28 days before the start of screening
Trial locations and contacts
38 sites in 8 countries.
38 sites in 8 countries
United States16 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109-0666
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Medical University of South Carolina (MUSC); MUSC Pulmonary
Charleston, South Carolina, 29425
Cardio-Pulmonary Associates of St. Luke's Hospital
Chesterfield, Missouri, 63017
UC Health Clinical Trials Office
Cincinnati, Ohio, 45267
Inova Health Care Services; Advanced Lung Disease Transplant Program
Falls Church, Virginia, 22042
Pulmonix LLC
Greensboro, North Carolina, 27403
David Geffen School of Medicine at UCLA;Division of Pulmonary & Critical Care/ Department of Medic
Los Angeles, California, 90095-1690
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Mount Sinai School of Medicine
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
Creighton University
Omaha, Nebraska, 68131
John A. Butler, M.D. - Oregon Pulmonary Associates
Portland, Oregon, 97225
Sarasota Memorial Hospital
Sarasota, Florida, 34239
Stanford University School of Medicine ; Pulmonary/Critical Care Medicine
Stanford, California, 94305
Atlantic Respiratory Institute
Summit, New Jersey, 07901
Spain7 sites
Hospital del Henares; Medicina Interna. Unidad de Neumología
Coslada (Madrid), Madrid, 28822
Hospital Universitari de Bellvitge ; Servicio de Neumologia
L'Hospitalet de Llobregat, Barcelona, 08097
Complejo Asistencial Universitario de Leon; Pneumology
León, 24071
Hospital Universitario La Princesa; Servicio de Neumologia
Madrid, 28006
Hospital Universitario de Canarias; Servicio de Neumologia
San Cristóbal de La Laguna, Tenerife, 38320
Hospital Universitario Virgen del Rocio; Servicio de Neumologia
Seville, 41013
Hospital General Universitario De Valencia; Servicio de Neumologia
Valencia, 46014
Italy4 sites
ASST DI MONZA; U O Clinica Pneumologica
Monza, Lombardy, 20900
A.O. Universitaria San Luigi Gonzaga di Orbassano; Malattie Apparato Respiratorio (MAR2)
Orbassano, Piedmont, 10043
Azienda Ospedaliero Universitaria Pisana; U.O. Pneumologia
Pisa, Tuscany, 56124
A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare
Siena, Tuscany, 53100
France3 sites
Hopital Avicenne; Pneumologie
Bobigny, 93000
Hopital Louis Pradel; Pneumologie
Bron, 69677
Hopital de Pontchaillou; Service de Pneumologie
Rennes, 35033
Germany3 sites
Fachkrankenhaus Coswig GmbH Zentrum f.Pneumologie Beatmungsmedizin Thorax-u.Gefäßchirurgie
Coswig, 01640
Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie
Essen, 45239
Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda
Fulda, 36043
Canada2 sites
South Health Campus/Alberta Health Services/ University of Calgary
Calgary, Alberta, T3M 1M4
University Health Network
Toronto, Ontario, M5G 2N2
Netherlands2 sites
Antonius Ziekenhuis; Dept of Lung Diseases
Nieuwegein, 3435 CM
Erasmus MC; Afdeling Longziekten
Rotterdam, 3000 CA
About this study
Official title: An Exploratory Multicenter, Open-Label, Single Arm Study of the Safety and Tolerability of Pirfenidone (Esbriet®) in Combination With Nintedanib (Ofev®) in Patients With Idiopathic Pulmonary Fibrosis
This clinical study will evaluate the safety and tolerability of combination treatment of nintedanib and pirfenidone in participants with IPF. Eligible participants must have received pirfenidone for at least 16 weeks on a stable dose. Nintedanib will be added on Day 1 of the study as a combination treatment for IPF for 24 weeks.
- 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
Also called Ofev
Participants with IPF will receive nintedanib at the 200-300 mg/day dose up to 24 weeks.
PirfenidoneDrug
Also called Esbriet
Participants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pirfenidone+Nintedanib | Experimental | Participants with IPF will receive pirfenidone at 1602-2403 milligrams per day (mg/day) dose and nintedanib at the 200-300 mg/day dose up to 24 weeks. Receives: Drug: Nintedanib; Drug: Pirfenidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Complete 24 Weeks of Combination Treatment on Pirfenidone at a Dose of 1602-2403 mg/Day and Nintedanib at a Dose of 200-300 mg/Day
Measured: Week 24
Secondary outcomes (4)
Percentage of Participants With Adverse Events and Serious Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Measured: Baseline up to Week 28
Percentage of Participants Who Discontinue Pirfenidone, Nintedanib, or Both Study Treatments Because of Adverse Events Before the Week 24 Visit
Measured: Baseline up to Week 24
Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib
Measured: Baseline up to Week 24
Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments
Measured: Baseline up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2015 (estimated)
- Study start14 Jan 2016
- Primary completion16 May 2017
- Study completion16 May 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 Hoffmann-La RocheThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02598193
- Sponsor's protocol ID
- MA29895
- Other IDs
- 2015-003280-11, 2015
- Status last verified
- May 2018
- First submitted
- 4 Nov 2015
- Last updated
- 13 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Flaherty KR, Fell CD, Huggins JT, Nunes H, Sussman R, Valenzuela C, Petzinger U, Stauffer JL, Gilberg F, Bengus M, Wijsenbeek M. Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis. Eur Respir J. 2018 Aug 2;52(2):1800230. doi: 10.1183/13993003.00230-2018. Print 2018 Aug.
PubMed 29946005
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Multicenter, Open-Label, Single Arm Study of the Safety and Tolerability of Pirfenidone (Esbriet®) in Combination With Nintedanib (Ofev®) in Patients With Idiopathic Pulmonary Fibrosis
- ClinicalTrials.gov ID
- NCT02598193
- Acronym / sponsor ID
- MA29895
- Conditions
- Idiopathic Pulmonary Fibrosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 14 Jan 2016 (actual)
- Primary completion
- 16 May 2017 (actual)
- Study completion
- 16 May 2017 (actual)
- First posted
- 5 Nov 2015 (estimated)
- Results
- Posted 13 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical study will evaluate the safety and tolerability of combination treatment of nintedanib and pirfenidone in participants with IPF. Eligible participants must have received pirfenidone for at least 16 weeks on a stable dose. Nintedanib will be added on Day 1 of the study as a combination treatment for IPF for 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pirfenidone+Nintedanib | Experimental | Drug: Nintedanib, Drug: PirfenidoneParticipants with IPF will receive pirfenidone at 1602-2403 milligrams per day (mg/day) dose and nintedanib at the 200-300 mg/day dose up to 24 weeks. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participants who are on pirfenidone for at least 16 weeks and on a stable dose (defined as 1602-2403 mg/day) for at least 28 days at the start of Screening; the dose must be expected to remain in that range throughout the study
- Documented diagnosis of IPF, per the Investigator per using the criteria of the 2011 American Thoracic Society / European Respiratory Society / Japanese Respiratory Society / Latin American Thoracic Association guidelines
- Participants with percent predicted forced vital capacity (FVC) more than or equal to (>=) 50 percent (%) and percent predicted carbon monoxide diffusing capacity (DLco) >=30% at Screening
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1% per year, during the treatment period and for at least 3 months after the final Follow-up Visit
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least 4 months after the final Follow-up Visit
Key exclusion criteria (12 listed)
- Participants with clinical evidence of active infection
- Participant with any new or ongoing moderate or severe adverse reaction considered by the Investigator to be related to pirfenidone, or an pirfenidone treatment interruption in the 28 days before the start of Screening
- Any condition that is likely to result in death in the 12 months after the start of Screening
- Lung transplantation anticipated or any planned significant surgical intervention
- Known hypersensitivity to the active substance or any excipient of either pirfenidone or nintedanib
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 |
|---|---|---|
| NintedanibAlso: OfevParticipants with IPF will receive nintedanib at the 200-300 mg/day dose up to 24 weeks. | Drug | Pirfenidone+Nintedanib |
| PirfenidoneAlso: EsbrietParticipants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks. | Drug | Pirfenidone+Nintedanib |
Primary outcome
Percentage of Participants Who Complete 24 Weeks of Combination Treatment on Pirfenidone at a Dose of 1602-2403 mg/Day and Nintedanib at a Dose of 200-300 mg/Day
Time frame: Week 24
4 secondary outcomes
Percentage of Participants With Adverse Events and Serious Adverse Events
Time frame: Baseline up to Week 28
Percentage of Participants Who Discontinue Pirfenidone, Nintedanib, or Both Study Treatments Because of Adverse Events Before the Week 24 Visit
Time frame: Baseline up to Week 24
Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib
Time frame: Baseline up to Week 24
Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments
Time frame: Baseline up to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29946005Flaherty KR, Fell CD, Huggins JT, Nunes H, Sussman R, Valenzuela C, Petzinger U, Stauffer JL, Gilberg F, Bengus M, Wijsenbeek M. Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis. Eur Respir J. 2018 Aug 2;52(2):1800230. doi: 10.1183/13993003.00230-2018. Print 2018 Aug.
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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.
Clinical Trials study director
Hoffmann-La Roche
38 sites in 8 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 Hoffmann-La Roche at 38 sites in 8 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 5 inclusion and 12 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 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Spain, Italy, France, Germany and 3 more countries. 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 Jun 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 Participants Who Complete 24 Weeks of Combination Treatment on Pirfenidone at a Dose of 1602-2403 mg/Day and Nintedanib at a Dose of 200-300 mg/Day (time frame: Week 24). 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 NCT02598193, 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 Jun 2018.