Study to Compare How the Body Absorbs, Distributes and Excretes the Drug Selitrectinib (BAY2731954) Given as Two Different Tablet Formulations or as Liquid Formulations Including the Effect of Food on the Absorption, Distribution or Excretion of the Different Formulations in Healthy Participants

Study Overview
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Brief Summary
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In this study, the researchers will compare 2 new tablet forms of BAY2731954 with liquid oral forms of BAY2731954. A maximum of 61 healthy volunteers aged 18 to 55 will be asked to participate. The study will have 2 parts. In part 1 researchers want to gather information how the body absorbs, distributes and excretes the drug BAY2731954 given as two different tablet formulations. Participants will take the study drugs on 3 days separated by breaks of at least 3 days between each intake. The duration of this study part will be in total of up to 6 weeks from first screening visit to follow-up visit. In part 2 of the study researchers want to study how the body absorbs, distributes and excretes the drug BAY2731954 given as two different tablet formulations with or without food or as 2 liquid oral formulations. Participants will take the study drugs on 4 days separated by breaks of at least 3 days between each intake. The duration of the second part of study part will be in total of up to 7 weeks from first screening visit to follow-up visit. During the study, researchers will collect blood and urine samples. In addition, doctors will check the participants' overall health. They will also ask the participants if they have any medical problems.

Official Title
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An Open-label, Phase I Study to Evaluate the Relative Bioavailability, Food Effect and Pharmacokinetic Linearity of 2 New Tablet Formulations (Adult and Pediatric) of Selitrectinib (BAY 2731954) in Relative to Oral Suspension and the Liquid Service Formulation in Healthy Adult Participants

Conditions
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Solid Tumors Harboring NTRK Fusion

Intervention / Treatment
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* Drug: Selitrectinib (BAY2731954) Adult tablet
* Drug: Selitrectinib (BAY2731954) Pediatric tablet
* Drug: Selitrectinib (BAY2731954) Oral solution
* Drug: Selitrectinib (BAY2731954) Oral suspension


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants who are overtly healthy as determined by the investigator or medically qualified designee based on medical evaluation including medical history, laboratory tests, physical, cardiac and neurologic examination Body mass index (BMI): ≥18.5 and ≤ 29.9 kg/m2, with body weight ≥50 kg Use of adequate contraception until 3 months after last study intervention Key Exclusion Criteria: Existing relevant diseases of vital organs (e.g. liver diseases, heart diseases), central nervous system (e.g. seizures) or other organs (e.g. diabetes mellitus). Medical history of risk factors for Torsades de pointes (e.g. family history of Long QT Syndrome) or other arrhythmias Known severe allergies, allergies requiring therapy with corticosteroids, non-allergic drug reactions, or (multiple) drug allergies (excluding untreated asymptomatic seasonal allergies such as non-severe hay fever during the time of study conduct). Regular use of medicines Regular alcohol consumption Smoking more than 5 cigarettes daily History of COVID-19 or current SARS-CoV-2 infection

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Part 1: sequential and non-randomized design Part 2: cross-over and randomized design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Group A<br>Participants will receive 3 single doses of selitrectinib in adult tablet formulation sequentially in 3 treatment periods. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Adult tablet<br>* Tablet, oral administration<br>|
| Experimental: Part 1: Group B<br>Participants will receive 3 single doses of selitrectinib in pediatric tablet formulation sequentially in 3 treatment periods. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Pediatric tablet<br>* Tablet, oral administration<br>|
| Experimental: Part 2 (Group A): Dose A-B-C-D<br>Participants will receive dose A, B, C and D sequentially. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Adult tablet<br>* Tablet, oral administration<br>Drug: Selitrectinib (BAY2731954) Oral solution<br>* Oral solution after reconstitution<br>Drug: Selitrectinib (BAY2731954) Oral suspension<br>* Oral suspension after reconstitution<br>|
| Experimental: Part 2 (Group A): Dose B-C-A-D<br>Participants will receive dose B, C, A and D sequentially. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Adult tablet<br>* Tablet, oral administration<br>Drug: Selitrectinib (BAY2731954) Oral solution<br>* Oral solution after reconstitution<br>Drug: Selitrectinib (BAY2731954) Oral suspension<br>* Oral suspension after reconstitution<br>|
| Experimental: Part 2 (Group A): Dose C-A-B-D<br>Participants will receive dose C, A, B and D sequentially. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Adult tablet<br>* Tablet, oral administration<br>Drug: Selitrectinib (BAY2731954) Oral solution<br>* Oral solution after reconstitution<br>Drug: Selitrectinib (BAY2731954) Oral suspension<br>* Oral suspension after reconstitution<br>|
| Experimental: Part 2 (Group B): Dose A-B-C-D<br>Participants will receive dose A, B, C and D sequentially. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Pediatric tablet<br>* Tablet, oral administration<br>Drug: Selitrectinib (BAY2731954) Oral suspension<br>* Oral suspension after reconstitution<br>|
| Experimental: Part 2 (Group B): Dose B-D-A-C<br>Participants will receive dose B, D, A and C sequentially. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Pediatric tablet<br>* Tablet, oral administration<br>Drug: Selitrectinib (BAY2731954) Oral suspension<br>* Oral suspension after reconstitution<br>|
| Experimental: Part 2 (Group B): Dose C-A-D-B<br>Participants will receive dose C, A, B and D sequentially. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Pediatric tablet<br>* Tablet, oral administration<br>Drug: Selitrectinib (BAY2731954) Oral suspension<br>* Oral suspension after reconstitution<br>|
| Experimental: Part 2 (Group B): Dose D-C-B-A<br>Participants will receive dose D, C, B and A sequentially. The washing-out period between each dose is at least 3 days | Drug: Selitrectinib (BAY2731954) Pediatric tablet<br>* Tablet, oral administration<br>Drug: Selitrectinib (BAY2731954) Oral suspension<br>* Oral suspension after reconstitution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area under the plasma concentration vs. time curve from 0 to infinity after single dose To evaluate the pharmacokinetic linearity of selitrectinib after a single dose of adult tablet and pediatric tablet and to evaluate the relative bioavailability of adult tablet and pediatric tablet formulation vs oral suspension formulation and the food effect on the bioavailability of 2 new tablet formulations | Up to 48 hours after dosing | 
| AUC(0-24) | Area under the plasma concentration vs. time curve from 0 to 24 hours after single dose To evaluate the pharmacokinetic linearity of selitrectinib after a single dose of adult tablet and pediatric tablet and to evaluate the relative bioavailability of adult tablet and pediatric tablet formulation vs oral suspension formulation and the food effect on the bioavailability of 2 new tablet formulations | Up to 24 hours after dosing | 
| Cmax | Maximum observed drug concentration in measured matrix after single dose administration To evaluate the pharmacokinetic linearity of selitrectinib after a single dose of adult tablet and pediatric tablet and to evaluate the relative bioavailability of adult tablet and pediatric tablet formulation vs oral suspension formulation and the food effect on the bioavailability of 2 new tablet formulations | Up to 48 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area under the plasma concentration vs. time curve from 0 to infinity after single dose. To evaluate the relative bioavailability of adult tablet and pediatric tablet formulation vs oral solution | Up to 48 hours after dosing | 
| AUC(0-24) | Area under the plasma concentration vs. time curve from 0 to 24 hours after single dose To evaluate the relative bioavailability of adult tablet and pediatric tablet formulation vs oral solution | Up to 24 hours after dosing | 
| Cmax | Maximum observed drug concentration in measured matrix after single dose administration To evaluate the relative bioavailability of adult tablet and pediatric tablet formulation vs oral solution | Up to 48 hours after dosing | 
| Number of participants with treatment emergent adverse events and severity of treatment emergent adverse events | Adverse events that occur or worsen after the first dose of study medication | Up to 7 weeks | 
| Incidence of laboratory abnormalities, based on clinical safety laboratory assessments | Hematology, clinical chemistry and urinalysis test results | Up to 7 weeks | 
| Ventricular rate |  | Up to 7 weeks | 
| ECG PR interval |  | Up to 7 weeks | 
| ECG QT interval |  | Up to 7 weeks | 
| ECG QRS duration |  | Up to 7 weeks | 
| Blood pressure in mmHg |  | Up to 7 weeks | 
| Heart rate in bpm | bpm: beats per minute | Up to 7 weeks | 
| Body temperature in Celsius |  | Up to 7 weeks | 
| Respiratory rate in breaths/min |  | Up to 7 weeks |