Exploratory Study of Inhaled Afatinib Dimaleate PK Profile (EDDIS-a1)

May 30, 2026 updated by: Petrov, Andrey

A Phase I Pilot Study to Evaluate the Bioequivalence, Pharmacokinetics, and Safety of Inhaled Afatinib Dimaleate Compared to the Reference Oral Afatinib Dimaleate in Healthy Smoking Volunteers (EDDIS-a1)

This is a pilot Phase I open-label randomized single-dose two-period crossover study (in the EDDIS project) evaluating the bioequivalence, pharmacokinetics (PK), safety, and tolerability of inhaled afatinib dimaleate compared with the reference oral afatinib dimaleate in healthy volunteer smokers.

The study will enroll healthy adult volunteers smoker to assess the systemic exposure and lung deposition of inhaled afatinib dimaleate. Participants will receive both the test inhaled formulation and the reference oral formulation in separate periods with delayed phase between treatments.

Key endpoints include maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), and lung deposition assessed via bronchoalveolar lavage (BAL), frequency of occurrence of side effects and cases of toxicity during the studies

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Participants will receive either a single dose of inhaled afatinib dimaleate or a 40 mg oral dose of afatinib dimaleate in a randomized sequence, with a 7-day washout period between treatments.

The inhaled formulation of afatinib dimaleate is administered via a single-use, maintenance-free ultrasonic nebulizer (by SWITZERLAND TEAM) that generates aerosol particles of a defined size, ensuring predictable bioavailability and targeted alveolar deposition. Each inhalation session consists of a predefined number of physiological breaths, facilitating efficient drug uptake into the lungs at therapeutically relevant doses.

Key assessments include blood sampling for pharmacokinetic (PK), LC-MS/MS, analysis, bronchoalveolar lavage (BAL) to evaluate pulmonary drug deposition, and spirometry to assess pulmonary safety.tests, CT.

The investigators aim to obtain data on the role of pulmonary P-glycoprotein (P-gp) transporters in actively expelling afatinib dimaleate back into the alveolar space, as well as its metabolism by cytochrome P450 enzymes (CYP3A4) during inhalation.

Additionally, statistically significant data on both drug lung deposition (DLD) and drug-induced lung injury (DILI) will be analyzed.

Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-∞), will be evaluated through plasma sampling. BAL will be performed in a subset of participants to assess direct pulmonary drug deposition. Safety and tolerability will be monitored through adverse event reporting, laboratory testing, and spirometry.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy male and female volunteers aged 21 to 55 years
  • Body mass index (BMI) from 18.5 to 30.0 kg/m²
  • Smokers or people who use e-cigarettes or vapes
  • No history of serious lung disease or respiratory disorders
  • No history of EGFR-targeted therapy or chemotherapy
  • Ability to give informed consent and comply with study procedures

Exclusion Criteria:

  • Pregnancy or lactation. (for female participants - 2 negative tests 10 days and 3 days before the start of the study)
  • Significant cardiovascular, hepatic, renal or neurological disorders. (ECG 30 days or earlier before the start of the study)
  • Recent use of any study drug (within 30 days) or prescription drugs that may affect the metabolism of afatinib
  • Known hypersensitivity to afatinib, its salts or derivatives of afatinib or related compounds
  • Рarticipation in other studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Afatinib Dimaleate inhalation form (liquid for inhalation)
Single-dose administration of inhaled afatinib dimaleate via an ultrasonic inhaler (healthy volunteer smokers only)
Drug: Afatinib Dimaleat
printed capsule containing 40 mg afatinib dimaleate
Other Names:
  • Gilotrif
  • BIBW2992 Dimaleate
  • Afatinib Dimaleate
Biological: inhalation of afatinib dimaleate
inhalation stable form of afatinib dimaleate at an equivalent therapeutic dose in a single-use maintenance-free ultrasonic inhaler with controlled frequency and number of inhalations
Other Names:
  • BIBW2992 Dimaleate
  • Afatinib Dimaleate
Active Comparator: Reference Afatinib Dimaleate
Single oral administration of reference afatinib dimaleate 40 mg capsule (healthy volunteer smokers only)
Drug: Afatinib Dimaleat
printed capsule containing 40 mg afatinib dimaleate
Other Names:
  • Gilotrif
  • BIBW2992 Dimaleate
  • Afatinib Dimaleate
Biological: inhalation of afatinib dimaleate
inhalation stable form of afatinib dimaleate at an equivalent therapeutic dose in a single-use maintenance-free ultrasonic inhaler with controlled frequency and number of inhalations
Other Names:
  • BIBW2992 Dimaleate
  • Afatinib Dimaleate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax (maximum observed plasma concentration)
Time Frame: up to 48 hours post-dose
quantitative measurement of afatinib dimaleate in plasma
up to 48 hours post-dose
afatinib dimaleate urinary concentrations
Time Frame: up to 96 hours
quantitative measurement of afatinib dimaleate in urine of inhaled and oral afatinib dimaleate
up to 96 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC (Area Under the Plasma Concentration-Time Curve)
Time Frame: up to 48 hours post-dose/inhalations
the total afatinib dimalete exposure integrated over time
up to 48 hours post-dose/inhalations

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of afatinib dimaleate concentration in blood
Time Frame: up to 96 hours
LC-MS/MS (liquid chromatography with selective mass analysis)
up to 96 hours
Median percentage of total neutrophils relative to absolute neutrophil count
Time Frame: up to 96 hours

BAL (bronchoalveolar lavage)

CAUTION! Bronchoalveolar lavage (BAL) should be distinguished from bronchial lavage (when a saline solution is injected into the large airways or bronchi and the fluid is then aspirated for analysis)
up to 96 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Petrov, Andrey

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 9, 2025

Primary Completion (Actual)

May 25, 2026

Study Completion (Actual)

May 25, 2026

Study Registration Dates

First Submitted

March 2, 2025

First Submitted That Met QC Criteria

March 26, 2025

First Posted (Actual)

March 27, 2025

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

May 30, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 233-1-10AfD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma

Clinical Trials on Afatinib Dimaleat

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Russia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe