NCT06897735

Exploratory Study of Inhaled Afatinib Dimaleate PK Profile

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)

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Petrov, Andrey · Academic / Other
• Sex: All
• Age: 21 Years – 55 Years
• Healthy volunteers: Accepted

Summary

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

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.

Conditions

• Lung Cancer
• Oral Cancer
• Melanoma

Interventions

Type	Name	Description
DRUG	Afatinib Dimaleat	printed capsule containing 40 mg 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

Timeline

• Start date: 2025-11-09
• Primary completion: 2026-03-25
• Completion: 2026-05-07
• First posted: 2025-03-27
• Last updated: 2025-11-18

Locations

1 site across 1 country: New Zealand

Regulatory

• FDA-regulated drug study