Mass Balance and Pharmacokinetics Study of Derazantinib in Healthy Male Subjects

NCT04098692 | Completed Phase 1

• 1 other identifier: DZB-CS-102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (12)

• 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

Study Arms (1)

Single-Arm: Derazantinib (Part 1 and Part 2)

EXPERIMENTAL

* 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; Drug: [14C]-Derazantinib solution for infusion; Drug: [14C]-Derazantinib capsule

Interventions

Derazantinib capsule DRUG

300 mg derazantinib oral administration (3x100 mg capsules)

Single-Arm: Derazantinib (Part 1 and Part 2)

[14C]-Derazantinib solution for infusion DRUG

100 μg \[14C\]-derazantinib intravenous administration

Single-Arm: Derazantinib (Part 1 and Part 2)

[14C]-Derazantinib capsule DRUG

300 mg \[14C\]-derazantinib oral administration (3x100 mg capsules)

Single-Arm: Derazantinib (Part 1 and Part 2)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (1)

Quotient Sciences, Ruddington

Nottingham, United Kingdom

Location

MeSH Terms

Interventions

derazantinib

Study Officials

• Nand Singh, MD

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: September 23, 2019
• Study Start: August 8, 2019
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: January 19, 2021

Record last verified: 2021-01

Locations

GB (1)