Ignite Creation Date:
2025-12-24 @ 10:03 PM
Ignite Modification Date:
2026-01-01 @ 4:16 PM
Study NCT ID:
NCT06897735
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-11-18
First Post:
2025-03-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Exploratory Study of Inhaled Afatinib Dimaleate PK Profile
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D009062', 'term': 'Mouth Neoplasms'}, {'id': 'D008545', 'term': 'Melanoma'}], 'ancestors': [{'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}, {'id': 'D009059', 'term': 'Mouth Diseases'}, {'id': 'D009057', 'term': 'Stomatognathic Diseases'}, {'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018326', 'term': 'Nevi and Melanomas'}, {'id': 'D012878', 'term': 'Skin Neoplasms'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077716', 'term': 'Afatinib'}], 'ancestors': [{'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011799', 'term': 'Quinazolines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': '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.\n\nInhaled 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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 24}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-11-09', 'type': 'ESTIMATED'}, 'statusVerifiedDate': '2025-11', 'completionDateStruct': {'date': '2026-05-07', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-16', 'studyFirstSubmitDate': '2025-03-02', 'studyFirstSubmitQcDate': '2025-03-26', 'lastUpdatePostDateStruct': {'date': '2025-11-18', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-03-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-03-25', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Determination of afatinib dimaleate concentration in blood', 'timeFrame': 'up to 96 hours', 'description': 'LC-MS/MS (liquid chromatography with selective mass analysis)'}, {'measure': 'Median percentage of total neutrophils relative to absolute neutrophil count', 'timeFrame': 'up to 96 hours', 'description': 'BAL (bronchoalveolar lavage)\n\nCAUTION! 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)'}], 'primaryOutcomes': [{'measure': 'Cmax (maximum observed plasma concentration)', 'timeFrame': 'up to 48 hours post-dose', 'description': 'quantitative measurement of afatinib dimaleate in plasma'}, {'measure': 'afatinib dimaleate urinary concentrations', 'timeFrame': 'up to 96 hours', 'description': 'quantitative measurement of afatinib dimaleate in urine of inhaled and oral afatinib dimaleate'}], 'secondaryOutcomes': [{'measure': 'AUC (Area Under the Plasma Concentration-Time Curve)', 'timeFrame': 'up to 48 hours post-dose/inhalations', 'description': 'the total afatinib dimalete exposure integrated over time'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Afatinib Dimaleate', 'BIBW2992 Dimaleate', 'GIOTRIF', 'GILOTRIF'], 'conditions': ['Lung Cancer', 'Oral Cancer', 'Melanoma']}, 'descriptionModule': {'briefSummary': '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.\n\nThe 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.\n\nKey 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', 'detailedDescription': '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.\n\nThe 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.\n\nKey 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.\n\nThe 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.\n\nAdditionally, statistically significant data on both drug lung deposition (DLD) and drug-induced lung injury (DILI) will be analyzed.\n\nPharmacokinetic 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '21 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy male and female volunteers aged 21 to 55 years\n* Body mass index (BMI) from 18.5 to 30.0 kg/m²\n* Smokers or people who use e-cigarettes or vapes\n* No history of serious lung disease or respiratory disorders\n* No history of EGFR-targeted therapy or chemotherapy\n* Ability to give informed consent and comply with study procedures\n\nExclusion Criteria:\n\n* Pregnancy or lactation. (for female participants - 2 negative tests 10 days and 3 days before the start of the study)\n* Significant cardiovascular, hepatic, renal or neurological disorders. (ECG 30 days or earlier before the start of the study)\n* Recent use of any study drug (within 30 days) or prescription drugs that may affect the metabolism of afatinib\n* Known hypersensitivity to afatinib, its salts or derivatives of afatinib or related compounds\n* Рarticipation in other studies'}, 'identificationModule': {'nctId': 'NCT06897735', 'acronym': 'EDDIS-a1', 'briefTitle': 'Exploratory Study of Inhaled Afatinib Dimaleate PK Profile', 'organization': {'class': 'OTHER', 'fullName': 'Petrov, Andrey'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': '233-1-10AfD'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Afatinib Dimaleate inhalation form (liquid for inhalation)', 'description': 'Single-dose administration of inhaled afatinib dimaleate via an ultrasonic inhaler (healthy volunteer smokers only)', 'interventionNames': ['Drug: Afatinib Dimaleat', 'Biological: inhalation of afatinib dimaleate']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Reference Afatinib Dimaleate', 'description': 'Single oral administration of reference afatinib dimaleate 40 mg capsule (healthy volunteer smokers only)', 'interventionNames': ['Drug: Afatinib Dimaleat', 'Biological: inhalation of afatinib dimaleate']}], 'interventions': [{'name': 'Afatinib Dimaleat', 'type': 'DRUG', 'otherNames': ['BIBW2992 Dimaleate', 'Gilotrif', 'Afatinib Dimaleate'], 'description': 'printed capsule containing 40 mg afatinib dimaleate', 'armGroupLabels': ['Afatinib Dimaleate inhalation form (liquid for inhalation)', 'Reference Afatinib Dimaleate']}, {'name': 'inhalation of afatinib dimaleate', 'type': 'BIOLOGICAL', 'otherNames': ['Afatinib Dimaleate', 'BIBW2992 Dimaleate'], 'description': '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', 'armGroupLabels': ['Afatinib Dimaleate inhalation form (liquid for inhalation)', 'Reference Afatinib Dimaleate']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Auckland', 'country': 'New Zealand', 'contacts': [{'role': 'CONTACT', 'email': 'trials@swissbio.zuerich', 'phone': '+64272550534 (SMS Only)'}, {'name': 'Central Contact', 'role': 'CONTACT', 'email': 'info@swissbio.zuerich'}], 'facility': 'Central Contact', 'geoPoint': {'lat': -36.84853, 'lon': 174.76349}}], 'centralContacts': [{'name': 'Ruslan Lytvyn', 'role': 'CONTACT', 'email': 'rlytvyn@swissbio.zuerich', 'phone': '+64272550534'}, {'name': 'Shalina Muller', 'role': 'CONTACT', 'email': 'irb@mail.ch', 'phone': '+41766165523'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Petrov, Andrey', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}