Solid Tumors Harboring NTRK Fusion
Conditions
Brief summary
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.
Interventions
DRUGSelitrectinib (BAY2731954) Adult tablet
Tablet, oral administration
DRUGSelitrectinib (BAY2731954) Pediatric tablet
Tablet, oral administration
DRUGSelitrectinib (BAY2731954) Oral solution
Oral solution after reconstitution
DRUGSelitrectinib (BAY2731954) Oral suspension
Oral suspension after reconstitution
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Part 1: sequential and non-randomized design Part 2: cross-over and randomized design
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC | Up to 48 hours after dosing | 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 |
| AUC(0-24) | Up to 24 hours after dosing | 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 |
| Cmax | Up to 48 hours after dosing | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment emergent adverse events and severity of treatment emergent adverse events | Up to 7 weeks | Adverse events that occur or worsen after the first dose of study medication |
| Incidence of laboratory abnormalities, based on clinical safety laboratory assessments | Up to 7 weeks | Hematology, clinical chemistry and urinalysis test results |
| Ventricular rate | Up to 7 weeks | — |
| ECG PR interval | Up to 7 weeks | — |
| ECG QT interval | Up to 7 weeks | — |
| AUC | Up to 48 hours after dosing | 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 |
| Blood pressure in mmHg | Up to 7 weeks | — |
| Heart rate in bpm | Up to 7 weeks | bpm: beats per minute |
| Body temperature in Celsius | Up to 7 weeks | — |
| Respiratory rate in breaths/min | Up to 7 weeks | — |
| ECG QRS duration | Up to 7 weeks | — |
| AUC(0-24) | Up to 24 hours after dosing | 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 |
| Cmax | Up to 48 hours after dosing | 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 |
Countries
United States
Outcome results
None listed