A Relative Bioavailability and Food Effect Study of TYRA-300-B01 Capsule and Tablet Formulations in Healthy Adult Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the relative bioavailability of capsule and tablet formulations of TYRA-300-B01, and to evaluate the safety, tolerability, and food effect of TYRA-300-B01 tablets in healthy adult participants.

Detailed Description
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This is a Phase 1, multi-cohort trial studying TYRA-300-B01, a novel, potent fibroblast growth factor receptor (FGFR) 3-selective tyrosine kinase inhibitor, in healthy, adult participants. The purpose of this study is to evaluate the relative bioavailability of capsule and tablet formulations of TYRA-300-B01, and to evaluate the safety, tolerability, and food effect of TYRA-300-B01 tablets in healthy adult participants.

Official Title
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A Phase 1, Multi-cohort, Open-label Study to Evaluate the Relative Bioavailability of Capsule and Tablet Formulations of TYRA-300-B01, and to Evaluate the Safety, Tolerability, and Food Effect of TYRA-300-B01 Tablets in Healthy Adult Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: TYRA-300-B01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females of non-childbearing potential, between 18 and 55 years of age In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory assessments Body mass index (BMI) 18 to 32 kg/m^2 (inclusive) Cohorts 1 and 2 ethnicity requirements: none Cohort 3 ethnicity requirements: first- or second-generation Japanese participants Exclusion Criteria: Significant history of any hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, immunologic, musculoskeletal disease, or allergic disease (as determined by the Investigator) Any ocular condition likely to increase the risk of eye toxicity Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300-B01 Females of child-bearing potential and males who plan to father a child while enrolled in this study

Ages Eligible for Study
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Minimum Age: 26 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bioavailability Tablet vs Capsule Formulation<br>TYRA-300-B01 single oral dose of tablet or capsule crossover followed by twice-daily tablet dosing | Drug: TYRA-300-B01<br>* TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.<br>|
| Experimental: Food Effect Tablet Formulation<br>TYRA-300-B01 single oral dose of tablet in the fed and fasted state | Drug: TYRA-300-B01<br>* TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.<br>|
| Experimental: Pharmacokinetic Tablet Formulation<br>TYRA-300-B01 single oral dose | Drug: TYRA-300-B01<br>* TYRA-300 is an oral, novel potent FGFR 3-selective tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics single-dose Cmax | maximum plasma concentration (Cmax) | Up to 48 hours post-dose | 
| Pharmacokinetics multiple-dose Cmax | maximum steady-state plasma concentration (Cmax) | Up to 24 hours post-dose | 
| Pharmacokinetics multiple-dose Cmin | average steady-state trough plasma concentration (Cmin) | Up to 24 hours post-dose | 
| Pharmacokinetics single dose Tmax | time to reach maximum plasma concentration (Tmax) | Up to 48 hours post-dose | 
| Pharmacokinetics single and multiple dose AUC | area under the plasma concentration-time curve (AUC) | Up to 48 hours post-dose | 
| Pharmacokinetics single dose CL/F | apparent total clearance (CL/F) | Up to 48 hours post-dose | 
| Pharmacokinetics single dose Vz/F | apparent volume of distribution (Vz/F) | Up to 48 hours post-dose | 
| Pharmacokinetics single dose t1/2 | half-life of TYRA-300 | Up to 48 hours post-dose | 
| Pharmacokinetics multiple-dose RCmax | accumulation ratio for Cmax (RCmax) | Up to 24 hours post-dose | 
| Pharmacokinetics multiple-dose RAUC | accumulation ratio for AUC | Up to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | number of participants with adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs) as a measure of safety and tolerability | Initiation of study treatment up to 7-days post treatment | 
| Safety and tolerability | Frequency in changes in laboratory parameters and physical signs of toxicity | Initiation of study treatment up to 7-days post treatment |