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NCT02579603

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

Completed Phase 4 Results posted Last updated 13 February 2018
What this trial tests

Phase 4 trial testing Nintedanib in Idiopathic Pulmonary Fibrosis in 105 participants. Completed in 31 January 2017.

Timeline
16 October 2015
Primary endpoint
3 January 2017
31 January 2017

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment105
Start date16 October 2015
Primary completion3 January 2017
Estimated completion31 January 2017
Sites23 locations across France, Italy, Netherlands, Germany, Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

40 and older, any sex, with Idiopathic Pulmonary Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Patients With On-treatment Gastrointestinal (GI) AEs (SOC GI Disorders) From Baseline to Week 12 Primary · 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).

GroupValue95% CI
Nintedanib52.9
Nintedanib + Pirfenidone69.8
Predose Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline, Weeks 2 and 4 Secondary · baseline, prior to intake of study medication on week 2 and week 4

Predose plasma concentrations at steady state (Cpre,ss) of nintedanib at baseline (Visit 3), Week 2 (Visit 4) and Week 4 (Visit 5)

baseline
GroupValue95% CI
Nintedanib7.08± 56.0
Nintedanib + Pirfenidone7.65± 72.5
Week 2
GroupValue95% CI
Nintedanib7.25± 52.7
Nintedanib + Pirfenidone8.17± 69.8
Week 4
GroupValue95% CI
Nintedanib5.92± 73.5
Nintedanib + Pirfenidone7.13± 63.9
Predose Plasma Concentrations at Steady State (Cpre,ss) of Pirfenidone Secondary · Prior to intake of study medication on week 2 and week 4

Predose plasma concentrations at steady state (Cpre,ss) of pirfenidone at Week 2 (Visit 4) and Week 4 (Visit 5)

Week 2
GroupValue95% CI
Nintedanib + Pirfenidone1120± 122
Week 4
GroupValue95% CI
Nintedanib + Pirfenidone1220± 90.7

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose administration of the study medication to 28 days after last drug administration; up to 124 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nintedanib
Serious: 5/51 (10%)
Deaths:
Nintedanib + Pirfenidone
Serious: 2/53 (4%)
Deaths:

Serious adverse events (8 terms)

ReactionSystemNintedanibNintedanib + Pirfenidone
Atrial flutterCardiac disorders
Pancreatitis acuteGastrointestinal disorders
PneumoniaInfections and infestations
Transient ischaemic attackNervous system disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosisRespiratory, thoracic and mediastinal disorders
Circulatory collapseVascular disorders
PhlebitisVascular disorders
Other adverse events (26 terms — click to expand)

ReactionSystemNintedanibNintedanib + Pirfenidone
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
HeadacheNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
BronchitisInfections and infestations
Abdominal discomfortGastrointestinal disorders
Abdominal painGastrointestinal disorders
NasopharyngitisInfections and infestations
Weight decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
Hepatocellular injuryHepatobiliary disorders
ContusionInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
DizzinessNervous system disorders
DysgeusiaNervous system disorders
Photosensitivity reactionSkin and subcutaneous tissue disorders

Most-reported serious reactions: Atrial flutter, Pancreatitis acute, Pneumonia, Transient ischaemic attack, Acute respiratory failure, Idiopathic pulmonary fibrosis, Circulatory collapse, Phlebitis.

Data from ClinicalTrials.gov NCT02579603 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Nintedanib with Add-on Pirfenidone in Idiopathic Pulmonary Fibrosis. Results of the INJOURNEY Trial.
    Vancheri C, Kreuter M, Richeldi L, Ryerson CJ, et al · · 2018 · cited 206× · PMID 28889759 · DOI 10.1164/rccm.201706-1301oc
  2. Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases.
    Lin SN, Mao R, Qian C, Bettenworth D, et al · · 2022 · cited 62× · PMID 34569264 · DOI 10.1152/physrev.00005.2021
  3. Role of pirfenidone in the management of pulmonary fibrosis.
    Meyer KC, Decker CA. · · 2017 · cited 46× · PMID 28435277 · DOI 10.2147/tcrm.s81141
  4. Efficacy and Safety of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis: An Update.
    Rodríguez-Portal JA. · · 2018 · cited 37× · PMID 29209910 · DOI 10.1007/s40268-017-0221-9
  5. Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD.
    Shumar JN, Chandel A, King CS. · · 2021 · cited 21× · PMID 34070297 · DOI 10.3390/jcm10112285
  6. Clinical use of nintedanib in patients with idiopathic pulmonary fibrosis.
    Hajari Case A, Johnson P. · · 2017 · cited 19× · PMID 28883926 · DOI 10.1136/bmjresp-2017-000192
  7. Cellular and Molecular Control of Lipid Metabolism in Idiopathic Pulmonary Fibrosis: Clinical Application of the Lysophosphatidic Acid Pathway.
    Nakamura Y, Shimizu Y. · · 2023 · cited 14× · PMID 36831215 · DOI 10.3390/cells12040548
  8. Ongoing Clinical Trials in Aging-Related Tissue Fibrosis and New Findings Related to AhR Pathways.
    Yu HX, Feng Z, Lin W, Yang K, et al · · 2022 · cited 8× · PMID 35656117 · DOI 10.14336/ad.2021.1105

Verify or expand the search:

Other trials of Nintedanib

Trials testing the same drug.

Other recruiting trials for Idiopathic Pulmonary Fibrosis

Currently open trials in the same condition.

Other Boehringer Ingelheim trials

Trials by the same sponsor.

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