A Study to Investigate 14C-bemcentinib in Healthy Male Subjects

NCT06469138 | Completed Phase 1 Results

• 1 other identifier: BGBC021
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The aims of this Study were to determine:

• How much of the Study Drug (bemcentinib) ends up in urine and faeces
• How much of the Study Drug and its breakdown products get into the bloodstream
• The breakdown products (metabolites) of the Study Drug
• The safety of the Study Drug and any side effects that might be associated with it.

Conditions

Non-Small Cell Lung Cancer; Metastatic Melanoma; Acute Myeloid Leukemia; Myelodysplastic Syndromes; Metastatic Pancreatic Cancer; Glioblastoma; Malignant Mesothelioma; COVID-19

Outcome Measures

Primary Outcomes (7)

• Total Radioactivity - Plasma Maximum Observed Concentration (Cmax)

  This endpoint will report the relevant data for the parameters assessed in order to measure total radioactivity in plasma (based upon plasma samples collected at set timepoints during the study). Analysis was derived from obtaining plasma samples from participants at set timepoints described and deriving PK parameters through the use of noncompartmental procedures in validated software (WinNonlin Version 8.3.5).

  Samples collected over a 2-week period: Days 1-8: Predose, 15 and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose, Days 8-15: 192, 216, 240, 264, 288, 312, and 336 hours post-dose

• Total Radioactivity - Whole Blood Maximum Observed Concentration (Cmax)

  This endpoint will report the relevant data for the parameters assessed in order to measure total radioactivity in whole blood (based upon whole blood samples collected at set timepoints during the study). Analysis was derived from obtaining whole blood samples from participants at set timepoints described and deriving PK parameters through the use of noncompartmental procedures in validated software (WinNonlin Version 8.3.5).

  Samples collected over a 2-week period: Days 1-8: Predose, 15 and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose, Days 8-15: 192, 216, 240, 264, 288, 312, and 336 hours post-dose

• Plasma Pharmacokinetic Parameters Bemcentinib - Maximum Observed Concentration (Cmax)

  Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for 14C-bemcentinib. This endpoint will report the summary of derived pharmacokinetic parameters for the maximum observed concentration (Cmax) of 14C-bemcentinib in plasma. Analysis was derived from obtaining plasma samples from participants at set timepoints described and deriving PK parameters through the use of noncompartmental procedures in validated software (WinNonlin Version 8.3.5).

  Samples collected over a 2-week period: Days 1-8: Predose, 15 and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose, Days 8-15: 192, 216, 240, 264, 288, 312, and 336 hours post-dose

• Plasma Pharmacokinetic Parameters Bemcentinib - Time to Maximum Observed Concentration (Tmax)

  Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for 14C-bemcentinib. This endpoint will report the summary of derived pharmacokinetic parameters for the time to maximum observed concentration (Tmax) of 14C-bemcentinib in plasma. Analysis was derived from obtaining plasma samples from participants at set timepoints described and deriving PK parameters through the use of noncompartmental procedures in validated software (WinNonlin Version 8.3.5).

  Samples collected over a 2-week period: Days 1-8: Predose, 15 and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose, Days 8-15: 192, 216, 240, 264, 288, 312, and 336 hours post-dose

• Plasma Pharmacokinetic Parameters Bemcentinib - Terminal Elimination Half-life (t1/2)

  Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for 14C-bemcentinib. This endpoint will report the summary of derived pharmacokinetic parameters for the terminal elimination half-life (t1/2) of 14C-bemcentinib in plasma. Analysis was derived from obtaining plasma samples from participants at set timepoints described and deriving PK parameters through the use of noncompartmental procedures in validated software (WinNonlin Version 8.3.5).

  Samples collected over a 2-week period: Days 1-8: Predose, 15 and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose, Days 8-15: 192, 216, 240, 264, 288, 312, and 336 hours post-dose

• Plasma Pharmacokinetic Parameters Bemcentinib - Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞)

  Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for 14C-bemcentinib. This endpoint will report the summary of derived pharmacokinetic parameters for the area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) of 14C-bemcentinib in plasma. Analysis was derived from obtaining plasma samples from participants at set timepoints described and deriving PK parameters through the use of noncompartmental procedures in validated software (WinNonlin Version 8.3.5).

  Samples collected over a 2-week period: Days 1-8: Predose, 15 and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose, Days 8-15: 192, 216, 240, 264, 288, 312, and 336 hours post-dose

• Plasma Pharmacokinetic Parameters Bemcentinib - Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)

  Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for 14C-bemcentinib. This endpoint will report the summary of derived pharmacokinetic parameters for the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-tlast) of 14C-bemcentinib in plasma. Analysis was derived from obtaining plasma samples from participants at set timepoints described and deriving PK parameters through the use of noncompartmental procedures in validated software (WinNonlin Version 8.3.5).

  Samples collected over a 2-week period: Days 1-8: Predose, 15 and 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose, Days 8-15: 192, 216, 240, 264, 288, 312, and 336 hours post-dose

Secondary Outcomes (5)

• Number of Participants With Adverse Events

  Collection of AEs occurs through ad hoc reporting from the participants from the point of signature of informed consent through to study completion (up to 5 weeks).

• Number of Participants Who Report a Change From Normal Range Values for Laboratory Safety Parameters (Serum Biochemistry, Serum Haematology or Urinalysis) From First Dose on Day 1 to Study Completion.

  From Day 1 to study completion (up to 5 weeks)

• Number of Participants Who Report a Change From Normal Range Values for Any of the Associated 12-Lead ECG Parameters From First Dose on Day 1 to Study Completion.

  From Day 1 to study completion (up to 5 weeks)

• Number of Participants Who Report a Change From Normal Range Values for Any of the Vital Signs Parameters From First Dose on Day 1 to Study Completion.

  From Day 1 to study completion (up to 5 weeks)

• Number of Participants Who Report a Change From Normal With Respect to Physical Examination Parameters From First Dose on Day 1 to Study Completion.

  From Day 1 to study completion (up to 5 weeks)

Study Arms (1)

Single Dose Cohort - 200 mg containing approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib

EXPERIMENTAL

This is the only treatment arm in this study. Up to 8 participants will receive a single oral dose of 200 mg containing approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib, 30 minutes after starting a standard high-fat breakfast.

Drug: Bemcentinib

Interventions

Bemcentinib DRUG

Each 200 mg dose contains approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib and is administered as a single dose on Day 1 of the study.

Also known as: BGB324

Single Dose Cohort - 200 mg containing approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib

Eligibility Criteria

• Age: 35 Years - 55 Years
• Gender Eligibility Details: As this study involves radiation exposures, as per the applicable regulatory guidance, the most relevant population for this study is healthy male volunteers.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males of any race, between 35 and 55 years of age, inclusive.
• Body mass index between 18.0 and 32.0 kg/m2, inclusive, and a total body weight between 50 and 100 kg, inclusive.
• In good health, determined by no clinically significant findings from medical history, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in and from the physical examination at check-in, as assessed by the investigator (or designee).
• No clinically significant abnormalities in 12-lead ECG determined within 28 days before dose of IMP including average PR \> 220 ms and QT interval corrected for heart rate using Fridericia's formula \>450 ms.
• No history of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia, left bundle branch block, or ventricular arrhythmia), atrial fibrillation, or history of familial long QT syndromes.
• Will agree to use contraception as detailed in the study protocol.
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
• History of a minimum of 1 bowel movement per day.

You may not qualify if:

• Medical conditions
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
• Positive hepatitis panel and/or positive human immunodeficiency virus test.
• Prior/concomitant therapy
• Administration of a COVID-19 vaccine in the past 30 days prior to dosing.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to check-in, unless deemed acceptable by the investigator (or designee).
• Use or intend to use any prescription medications/products within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee).
• Use or intend to use slow-release medications/products considered to still be active within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee).
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to check-in, unless deemed acceptable by the investigator (or designee).
• Prior/concurrent clinical study experience
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
• Subjects who have participated in any clinical study involving a radiolabelled investigational product within 12 months prior to check-in.
• Have previously completed or withdrawn from this study or any other study investigating bemcentinib, and have previously received bemcentinib.

Sponsors & Collaborators

• BerGenBio ASA: lead

Study Sites (1)

Labcorp Clinical Research Unit Ltd.

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Pancreatic Neoplasms; Glioblastoma; Mesothelioma, Malignant; COVID-19

Interventions

bemcentinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract 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; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Mesothelioma; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Results Point of Contact

• Title: BerGenBio Clinical Team
• Organization: BerGenBio ASA

registry.postings@bergenbio.com

+47 559 61 159

Study Officials

• Dr Brooks, MBChB

  Labcorp Clinical Research Unit Ltd.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: N/A - study is open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All participants will be assigned to active treatment and will be dosed within a single cohort of up to 8 participants (with 6 required to complete).

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 21, 2024
• Study Start: August 2, 2022
• Primary Completion: September 23, 2022
• Study Completion: September 23, 2022
• Last Updated: January 29, 2025
• Results First Posted: January 29, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)