A Study in Healthy Men to Test Whether BI 1015550 Influences the Amount of Nintedanib and Pirfenidone in the Blood

The Effect of Multiple Oral Doses of BI 1015550 on the Pharmacokinetics of Nintedanib and Pirfenidone Administered Single Dose to Healthy Male Subjects (Open-label, Two-period, Fixed-sequence Crossover Trial)

The main objective of this trial is to investigate the induction effect of multiple oral doses of BI 1015550 on the pharmacokinetics of nintedanib or pirfenidone.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 1015550; Drug: Nintedanib; Drug: Pirfenidone

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
2. Age of 18 to 55 years (inclusive)
3. Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
4. Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial

Exclusion Criteria:

1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (bpm)
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders (including severe renal or hepatic impairment)
6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
8. History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Reference treatment/Test treatment; In the reference (R) treatment (period 1, two days of treatment), a single dose of 267 mg pirfenidone was administered on Day 1 and a single dose of 100 mg nintedanib on Day 2. In the test (T) treatment (period 2, ten days of treatment), 18 mg nerandomilast were administered twice daily for 10 days (Day -6 to Day 4). A single dose of 267 mg pirfenidone was administered on Day 1 and a single dose of 100 mg nintedanib was administered on Day 2. A washout period of at least 72 hours separated the last drug administration in the reference period from the first drug administration in the test period.

Drug: BI 1015550; BI 1015550; Other Names: Nerandomilast; JASCAYD®; Drug: Nintedanib; Soft capsules; Other Names: Ofev®; Drug: Pirfenidone; Film-coated tablets; Other Names: Esbriet®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of Pirfenidone in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of pirfenidone in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Geometric least squares mean (adjusted geometric mean) and the standard error (actually adjusted geometric standard error) were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.	At 0, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 10, 12, 24 hours from pirfenidone administration (Period 1) and at 0, 0.30, 1, 1:30, 2, 3, 4, 6, 8, 10, 12, 24 hours from nerandomilast and pirfenidone administration (Period 2)
Area Under the Concentration-time Curve of Pirfenidone in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of pirfenidone in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Geometric least squares mean (adjusted geometric mean) and the standard error (actually adjusted geometric standard error) were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.	At 0, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 10, 12, 24 hours from pirfenidone administration (Period 1) and at 0, 0.30, 1, 1:30, 2, 3, 4, 6, 8, 10, 12, 24 hours from nerandomilast and pirfenidone administration (Period 2)
Maximum Measured Concentration of Pirfenidone in Plasma (Cmax)	Maximum measured concentration of pirfenidone in plasma (Cmax). Geometric least squares mean (adjusted geometric mean) and the standard error (actually adjusted geometric standard error) were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.	At 0, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 10, 12, 24 hours from pirfenidone administration (Period 1) and at 0, 0.30, 1, 1:30, 2, 3, 4, 6, 8, 10, 12, 24 hours from nerandomilast and pirfenidone administration (Period 2)
Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Geometric least squares mean (adjusted geometric mean) and the standard error (actually adjusted geometric standard error) were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.	At 24, 24:30, 25, 25:30, 26, 27, 28, 30, 32, 34, 36, 48, 60,72, 96 hours from pirfenidone administration (Period 1) and at 24, 24:30, 25, 25:30, 26, 27, 28, 30, 32, 34, 36, 48, 60,72, 96 hours from nerandomilast and pirfenidone administration (Period 2)
Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Geometric least squares mean (adjusted geometric mean) and the standard error (actually adjusted geometric standard error) were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.	At 24, 24:30, 25, 25:30, 26, 27, 28, 30, 32, 34, 36, 48, 60,72, 96 hours from pirfenidone administration (Period 1) and at 24, 24:30, 25, 25:30, 26, 27, 28, 30, 32, 34, 36, 48, 60,72, 96 hours from nerandomilast and pirfenidone administration (Period 2)
Maximum Measured Concentration of Nintedanib in Plasma (Cmax)	Maximum measured concentration of nintedanib in plasma (Cmax). Geometric least squares mean (adjusted geometric mean) and the standard error (actually adjusted geometric standard error) were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.	At 24, 24:30, 25, 25:30, 26, 27, 28, 30, 32, 34, 36, 48, 60,72, 96 hours from pirfenidone administration (Period 1) and at 24, 24:30, 25, 25:30, 26, 27, 28, 30, 32, 34, 36, 48, 60,72, 96 hours from nerandomilast and pirfenidone administration (Period 2)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: October 2, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Protein Kinase Inhibitors; pirfenidone; nintedanib; BI 1015550
• Other Study ID Numbers: 1305-0034; 2023-505522-34-00 (Registry Identifier: CTIS); U1111-1292-0376 (Registry Identifier: WHO registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No