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A Study to Investigate 14C-bemcentinib in Healthy Male Subjects (8479217)

B

BerGenBio

Status and phase

Completed
Phase 1

Conditions

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

Treatments

Drug: Bemcentinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT06469138
BGBC021

Details and patient eligibility

About

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.

Full description

This was a Phase 1, open-label, nonrandomized, single oral dose study in up to 8 healthy male subjects (with 6 required to complete the study).

Potential subjects were screened to assess their eligibility to enter the study within 28 days prior to dose administration. Up to 8 subjects were enrolled to ensure that 6 subjects completed the study. Subjects were admitted into the study site on Day -1. On the morning of Day 1, all subjects received 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.

Subjects were confined to the study site until at least Day 8. Subjects were discharged from the study site on Day 8 if the following discharge criteria were met:

·≥90% mass balance recovery, and

·<1% of the total radioactive dose is recovered in combined excreta (urine and feces)in 2 consecutive 24-hour periods.

If these discharge criteria were not met by Day 8, subjects were required to remain resident until discharge criteria are met, up to Day 15. If criteria were not met by Day 15, subjects were asked to collect 24-hour excreta samples on up to 2 further occasions on a nonresidential basis to allow extrapolation of urinary and fecal excretion. If needed, the 2 additional 24-hour nonresidential collections started on the morning of Days 22 and 29 (to be brought into the study site at the end of the collection interval on Days 23 and 30, respectively). If on the second occasion the subject still did not meet the desired criterion, then the subject was discharged from the study, per investigator and sponsor decision.

Subjects experiencing emesis during the first 4 hours post-dose were discharged on the same day from the study site, provided there were no safety concerns, and after discharge study procedures were performed.

The total duration of study participation for each subject (from screening to outpatient visit [if required]) was anticipated to be a maximum of approximately 58 days.

Enrollment

6 patients

Sex

Male

Ages

35 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  1. Males of any race, between 35 and 55 years of age, inclusive.
  2. Body mass index between 18.0 and 32.0 kg/m2, inclusive, and a total body weight between 50 and 100 kg, inclusive.
  3. 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).
  4. 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.
  5. 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.
  6. Will agree to use contraception as detailed in the study protocol.
  7. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
  8. History of a minimum of 1 bowel movement per day.

Exclusion criteria

Medical conditions

  1. 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).

  2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).

  3. 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).

  4. Positive hepatitis panel and/or positive human immunodeficiency virus test.

    Prior/concomitant therapy

  5. Administration of a COVID-19 vaccine in the past 30 days prior to dosing.

  6. 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).

  7. Use or intend to use any prescription medications/products within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee).

  8. 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).

  9. 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

  10. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.

  11. Subjects who have participated in any clinical study involving a radiolabelled investigational product within 12 months prior to check-in.

  12. Have previously completed or withdrawn from this study or any other study investigating bemcentinib, and have previously received bemcentinib.

    Diet and lifestyle

  13. Alcohol consumption of > 28 units per week for males. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.

  14. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check-in.

  15. History of alcoholism or drug/chemical abuse within 2 years prior to check-in.

  16. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or positive cotinine at screening or check-in.

  17. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to check-in.

    Other exclusions

  18. Receipt of blood products within 2 months prior to check-in.

  19. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.

  20. Poor peripheral venous access.

  21. Subjects with exposure to significant diagnostic or therapeutic radiation (eg, serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to check-in.

  22. Subjects who, in the opinion of the investigator (or designee), should not participate in this study.

Subjects may previously have been screened on a generic basis to determine their eligibility for inclusion in Phase 1 clinical studies conducted at the study site. If generic screening was performed within the specified study screening window, selected study-specific procedures will be repeated either at an additional screening visit or on admission to the study site on Day -1.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

6 participants in 1 patient group

Single Dose Cohort - 200 mg containing approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib
Experimental group
Description:
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.
Treatment:
Drug: Bemcentinib

Trial documents
1

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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