A Phase 1 Study to Investigate 14C-bemcentinib Following Single Oral Administration in Healthy Male Subjects

COVID-19 Clinical Trial

— 8479217  

Official title:

A Phase 1, Open-label, Nonrandomized Study to Investigate the Mass Balance Recovery and Metabolic Profile of 14C-bemcentinib Following Single Oral Administration in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06469138
• Other study ID #: BGBC021
• Status: Completed
• Phase: Phase 1
• Start date: August 2, 2022
• Est. completion date: September 23, 2022

Study information

• Verified date: June 2024
• Source: BerGenBio ASA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aims of this Study are 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.

Description:

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

Subjects will be confined to the study site until at least Day 8. Subjects will be discharged from the study site on Day 8 if the following discharge criteria are 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 are not met by Day 8, subjects will be required to remain resident until discharge criteria are met, up to Day 15. If criteria are not met by Day 15, subjects may be 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 will start 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 has still not met the desired criterion, then the subject will be discharged from the study, per investigator and sponsor decision.

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: September 23, 2022
• Est. primary completion date: September 23, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 35 Years to 55 Years

Eligibility

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 radiolabeled 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Bemcentinib
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.

Locations

Country	Name	City	State
United Kingdom	Labcorp Clinical Research Unit Ltd.	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
BerGenBio ASA

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Radioactivity Recovery (fet1-t2) - Urine	This endpoint will report the relevant data for the parameters assessed in order to measure total radioactivity recovery in urine (based upon urine samples collected at set timepoints during the study).	Samples collected over a 5-week period: Days 1 - 8: Predose (-3 to 0 hours), over 12-24 hour intervals up to 168 hours post-dose, Days 8-15: over 24 hour intervals up to 336 hours post-dose and 24 hour intervals between Days 22-23 & 29-30.
Primary	Total Radioactivity Recovery (fet1-t2) - Faeces	This endpoint will report the relevant data for the parameters assessed in order to measure total radioactivity recovery in faeces (based upon faeces samples collected at set timepoints during the study).	Samples collected over a 5-week period: Days 1 - 8: Predose (from check in to 0 hours), over 12-24 hour intervals up to 168 hours post-dose, Days 8-15: over 24 hour intervals up to 336 hours post-dose and 24 hour intervals between Days 22-23 & 29-30.
Primary	Total Radioactivity - Plasma	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).	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
Primary	Total Radioactivity - Whole Blood	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).	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
Primary	Plasma Pharmacokinetic Parameters - 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.	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
Primary	Plasma Pharmacokinetic Parameters - 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.	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
Primary	Plasma Pharmacokinetic Parameters - 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.	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
Primary	Plasma Pharmacokinetic Parameters - Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-8)	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 (AUC0-8) of 14C-bemcentinib in plasma.	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
Primary	Plasma Pharmacokinetic Parameters - 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.	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
Primary	Urinary Recovery - Percentage of the dose administered recovered over the time interval t1 to t2 (fet1-t2)	This endpoint will report the relevant data for the parameters assessed in order to measure urinary recovery (based upon urine samples collected at set timepoints during the study).	Samples collected over a 5-week period: Days 1 - 8: Predose (-3 to 0 hours), over 12-24 hour intervals up to 168 hours post-dose, Days 8-15: over 24 hour intervals up to 336 hours post-dose and 24 hour intervals between Days 22-23 & 29-30.
Secondary	Metabolic Profile & Identification - Bemcentinib - Plasma	This endpoint will report the relevant data for the parameters assessed in order to measure the metabolic profile of 14C-bemcentinib in plasma (based upon plasma samples collected at set timepoints during the study).	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	Metabolic Profile & Identification - Bemcentinib - Urine	This endpoint will report the relevant data for the parameters assessed in order to measure the metabolic profile of 14C-bemcentinib in urine (based upon urine samples collected at set timepoints during the study).	Samples collected over a 5-week period as follows: Days 1 - 8: Predose (-3 to 0 hours), over 12-24 hour intervals up to 168 hours post-dose, Days 8-15: over 24 hour intervals up to 336 hours post-dose and 24 hour intervals between Days 22-23 & 29-30.
Secondary	Metabolic Profile & Identification - Bemcentinib - Faeces	This endpoint will report the relevant data for the parameters assessed in order to measure the metabolic profile of 14C-bemcentinib in faeces (based upon faeces samples collected at set timepoints during the study).	Samples collected over a 5-week period as follows: Days 1 - 8: Predose (-3 to 0 hours), over 12-24 hour intervals up to 168 hours post-dose, Days 8-15: over 24 hour intervals up to 336 hours post-dose and 24 hour intervals between Days 22-23 & 29-30.
Secondary	Adverse Events	This secondary endpoint relates to the number of participants who report an adverse event (AE) during the study.	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).
Secondary	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.	This primary endpoint will report the number of participants who record a value which is deemed as outside of the normal range (clinically significant values only) for any of the serum biochemistry, serum haematology or urinalysis parameters as defined in the study protocol following first dose administration on Day 1 up to completion of the study.	From Day 1 to study completion (up to 5 weeks)
Secondary	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.	This primary endpoint will report the number of participants who record a value which is deemed as outside of the normal range (clinically significant values only) for any of the 12-Lead ECG parameters as defined in the study protocol following first dose administration on Day 1 up to completion of the study.	From Day 1 to study completion (up to 5 weeks)
Secondary	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.	This primary endpoint will report the number of participants who record a value which is deemed as outside of the normal range (clinically significant values only) for any of the vital signs parameters as defined in the study protocol following first dose administration on Day 1 up to completion of the study.	From Day 1 to study completion (up to 5 weeks)
Secondary	Number of participants who report a change from normal with respect to physical examination parameters from first dose on Day 1 to study completion.	This primary endpoint will report the number of participants who record a change which is deemed as outside of normal range (clinically significant changes only) for any of the physical examination parameters as defined in the study protocol following first dose administration on Day 1 up to completion of the study.	From Day 1 to study completion (up to 5 weeks)