Mass Balance and Pharmacokinetics Study of Derazantinib in Healthy Male Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Derazantinib capsule
* Drug: [14C]-Derazantinib solution for infusion
* Drug: [14C]-Derazantinib capsule


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |