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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT04771390

Collaborator

(none)

Enrollment

Locations

Arms

4.6

Actual Duration (Months)

Patients Per Site

5.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Harboring NTRK Fusion	Drug: Selitrectinib (BAY2731954) Adult tablet Drug: Selitrectinib (BAY2731954) Pediatric tablet Drug: Selitrectinib (BAY2731954) Oral solution Drug: Selitrectinib (BAY2731954) Oral suspension	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Part 1: sequential and non-randomized design Part 2: cross-over and randomized designPart 1: sequential and non-randomized design Part 2: cross-over and randomized design

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Feb 16, 2021

Actual Primary Completion Date :

May 20, 2021

Actual Study Completion Date :

Jul 6, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Group A 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 Tablet, oral administration
Experimental: Part 1: Group B 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 Tablet, oral administration
Experimental: Part 2 (Group A): Dose A-B-C-D 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 Tablet, oral administration Drug: Selitrectinib (BAY2731954) Oral solution Oral solution after reconstitution Drug: Selitrectinib (BAY2731954) Oral suspension Oral suspension after reconstitution
Experimental: Part 2 (Group A): Dose B-C-A-D 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 Tablet, oral administration Drug: Selitrectinib (BAY2731954) Oral solution Oral solution after reconstitution Drug: Selitrectinib (BAY2731954) Oral suspension Oral suspension after reconstitution
Experimental: Part 2 (Group A): Dose C-A-B-D 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 Tablet, oral administration Drug: Selitrectinib (BAY2731954) Oral solution Oral solution after reconstitution Drug: Selitrectinib (BAY2731954) Oral suspension Oral suspension after reconstitution
Experimental: Part 2 (Group B): Dose A-B-C-D 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 Tablet, oral administration Drug: Selitrectinib (BAY2731954) Oral suspension Oral suspension after reconstitution
Experimental: Part 2 (Group B): Dose B-D-A-C 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 Tablet, oral administration Drug: Selitrectinib (BAY2731954) Oral suspension Oral suspension after reconstitution
Experimental: Part 2 (Group B): Dose C-A-D-B 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 Tablet, oral administration Drug: Selitrectinib (BAY2731954) Oral suspension Oral suspension after reconstitution
Experimental: Part 2 (Group B): Dose D-C-B-A 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 Tablet, oral administration Drug: Selitrectinib (BAY2731954) Oral suspension Oral suspension after reconstitution

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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
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
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]
ECG QRS duration [Up to 7 weeks]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parexel International - Los Angeles	Glendale	California	United States	91206
2	PAREXEL International, Baltimore	Baltimore	Maryland	United States	21225

Sponsors and Collaborators

Bayer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Bayer

ClinicalTrials.gov Identifier:

NCT04771390

Other Study ID Numbers:

21416

First Posted:

Feb 25, 2021

Last Update Posted:

Aug 25, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Selitrectinib

Study Results

No Results Posted as of Aug 25, 2021