Exploratory Study of Inhaled Afatinib Dimaleate PK Profile

NCT06897735 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 233-1-10AfD
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Lung Cancer; Oral Cancer; Melanoma

Keywords

Afatinib Dimaleate; BIBW2992 Dimaleate; GIOTRIF; GILOTRIF

Outcome Measures

Primary Outcomes (2)

• Cmax (maximum observed plasma concentration)

  quantitative measurement of afatinib dimaleate in plasma

  up to 48 hours post-dose

• afatinib dimaleate urinary concentrations

  quantitative measurement of afatinib dimaleate in urine of inhaled and oral afatinib dimaleate

  up to 96 hours

Secondary Outcomes (1)

• AUC (Area Under the Plasma Concentration-Time Curve)

  up to 48 hours post-dose/inhalations

Other Outcomes (2)

• Determination of afatinib dimaleate concentration in blood

  up to 96 hours

• Median percentage of total neutrophils relative to absolute neutrophil count

  up to 96 hours

Study Arms (2)

Afatinib Dimaleate inhalation form (liquid for inhalation)

EXPERIMENTAL

Single-dose administration of inhaled afatinib dimaleate via an ultrasonic inhaler (healthy volunteer smokers only)

Drug: Afatinib Dimaleat; Biological: inhalation of afatinib dimaleate

Reference Afatinib Dimaleate

ACTIVE COMPARATOR

Single oral administration of reference afatinib dimaleate 40 mg capsule (healthy volunteer smokers only)

Drug: Afatinib Dimaleat; Biological: inhalation of afatinib dimaleate

Interventions

Afatinib Dimaleat DRUG

printed capsule containing 40 mg afatinib dimaleate

Also known as: BIBW2992 Dimaleate, Gilotrif, Afatinib Dimaleate

Afatinib Dimaleate inhalation form (liquid for inhalation); Reference Afatinib Dimaleate

inhalation of afatinib dimaleate BIOLOGICAL

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

Also known as: Afatinib Dimaleate, BIBW2992 Dimaleate

Afatinib Dimaleate inhalation form (liquid for inhalation); Reference Afatinib Dimaleate

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Petrov, Andrey: lead

Study Sites (1)

Central Contact

Auckland, New Zealand

Location

MeSH Terms

Conditions

Lung Neoplasms; Mouth Neoplasms; Melanoma

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Head and Neck Neoplasms; Mouth Diseases; Stomatognathic Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Ruslan Lytvyn

CONTACT

+64272550534; rlytvyn@swissbio.zuerich

Shalina Muller

CONTACT

+41766165523; irb@mail.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to receive inhaled or oral Afatinib Dimaleate treatment first, followed by a washout period, after which they will receive the alternative treatment Participants will receive either a single dose of inhaled afatinib dimaleate or 40 mg of oral afatinib dimaleate in a randomized sequence with a 7-day washout period between treatments. Inhaled afatinib dimaleate (liquid) is delivered using a maintenance-free, single-use ultrasonic nebulizer that generates aerosol particles of a defined size with the most efficient gas-dynamic characteristics for alveolar deposition. Each inhalation session consists of a defined number of breaths, which ensures the most efficient uptake of afatinib dimaleate aerosol in the lungs.

Study Record Dates

• First Submitted: March 2, 2025
• First Posted: March 27, 2025
• Study Start: November 9, 2025
• Primary Completion: March 25, 2026
• Study Completion: May 7, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)