Mass Balance and Pharmacokinetics Study of Derazantinib in Healthy Male Subjects

A Phase 1, Two-part, Open-label, Single-oral-dose Study to Investigate the Absolute Bioavailability and Absorption, Pharmacokinetics, Distribution, Metabolism, and Excretion of [14C]-Derazantinib in Healthy Male Subjects

This is a Phase 1, two-part, open-label, single centre, single arm study in healthy male subjects to investigate the oral PK, intravenous (IV) PK, mass balance, bioavailability and metabolites profiling and identification of derazantinib.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Derazantinib capsule; Drug: [14C]-Derazantinib solution for infusion; Drug: [14C]-Derazantinib capsule

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • Quotient Sciences, Ruddington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males
• Age 18 to ≤ 55 years (Part 1)
• Age 30 to ≤ 65 years (Part 2)
• Body mass index of 18.0 to 29.0 kg/m² and a minimum body weight of 50 kg
• Must have regular bowel movements
• Must agree to adhere to the contraception requirements

Exclusion Criteria:

• Male subjects with pregnant partners
• Subjects who have received any investigational medicine in a clinical research study within the previous 3 months
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee
• History of any drug or alcohol abuse in the 12 months prior to dosing
• Regular alcohol consumption in males > 21 units per week
• Smokers and users of e-cigarettes and nicotine replacement products and those who have used these products within the last 3 months
• Radiation exposure (diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study
• Participation in any study involving administration of any [14C]-labelled compound within 12 months prior to screening (Part 1 only)
• Excessive caffeine consumption within 14 days prior to screening, defined as 800 mg per day (approximately 6 large cups of coffee)
• Subjects who do not have suitable veins
• Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the Investigator
• Confirmed positive drugs of abuse test result
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results, or history of immunodeficiency diseases, including a positive HIV (ELISA and western blot) test result
• Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of < 70 mL/min using the Cockcroft-Gault equation
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder or current clinical evidence of any corneal or retinal disorder
• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
• Known hypersensitivity or allergy to natural rubber latex
• History of any food allergies
• History of clinically significant ECG abnormalities
• Familial history of sick-sinus syndrome
• Recent (within the last 3 years) and/or recurrent history of autonomic dysfunction
• Recent (within the last 3 years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma disease, treated or not treated)
• History of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, within the past 5 years
• Use of any prescription drugs (including vaccines), herbal supplements (such as St. John's Wort, homeopathic preparations), within 4 weeks prior to initial dosing, and/or over-the-counter medication, dietary supplements (vitamins and minerals included) within 2 weeks prior to initial dosing
• Donation or loss of 400 mL or more of blood and/or plasma within 3 months prior to initial dosing
• Any history or presence of frequent episodes of diarrhoea (defined as an increase of 4 to 6 stools per day over usual individual defecation pattern).
• Significant illness within 2 weeks prior to initial dosing
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardise the subject in case of participation in the study.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-Arm: Derazantinib (Part 1 and Part 2); Part 1: 300 mg Derazantinib oral administration followed by 100 μg [14C]-Derazantinib intravenous microdose; Part 2: 300 mg [14C]-Derazantinib oral administration	Drug: Derazantinib capsule; 300 mg derazantinib oral administration (3x100 mg capsules); Drug: [14C]-Derazantinib solution for infusion; 100 μg [14C]-derazantinib intravenous administration; Drug: [14C]-Derazantinib capsule; 300 mg [14C]-derazantinib oral administration (3x100 mg capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: Cmax	Assessment of the maximum observed plasma concentration (Cmax)	up to Day 50
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: Tmax	Assessment of the time from dosing at which Cmax was apparent (Tmax)	up to Day 50
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: t½	Assessment of the apparent terminal elimination half-life (t½)	up to Day 50
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: AUC0-t	Assessment of the area under the concentration-time curve from dosing to the last measurable concentration (AUC0-t)	up to Day 50
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: AUC0-inf	Assessment of the area under the concentration-time curve from dosing extrapolated to infinity (AUC0-inf)	up to Day 50
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: Tlast	Assessment of the time of the last measurable (positive) concentration (Tlast)	up to Day 50
Assessment of the PK of [14C]-derazantinib: CL	Assessment of the total clearance (CL)	up to Day 50
Assessment of the PK of [14C]-derazantinib: Vss	Assessment of the volume of distribution at steady state (Vss)	up to Day 50
Assessment of the PK of [14C]-derazantinib: Vd	Assessment of the volume of distribution (Vd)	up to Day 50
Assessment of the PK of derazantinib: CL/F	Apparent total clearance (CL/F)	up to Day 50
Assessment of the PK of derazantinib: F	Absolute bioavailability (F)	up to Day 50
Assessment of the rate and routes of excretion, and the mass balance of total radioactivity in urine and faeces and in all excreta	Assessment of total radioactivity by measuring the amount excreted (Ae), Ae as a percentage of the administered dose (%Ae), cumulative recovery (CumAe), and cumulative recovery expressed as a percentage of the dose (Cum%Ae)	up to Day 50

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Investigators: Principal Investigator: Nand Singh, MD, Quotient Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2019
• Primary Completion (Actual): November 18, 2019
• Study Completion (Actual): November 18, 2019

Study Registration Dates

• First Submitted: September 19, 2019
• First Submitted That Met QC Criteria: September 19, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: DZB-CS-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No