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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors Harboring NTRK Fusion
• Intervention / Treatment: Drug: Selitrectinib (BAY2731954) Adult tablet; Drug: Selitrectinib (BAY2731954) Pediatric tablet; Drug: Selitrectinib (BAY2731954) Oral solution; Drug: Selitrectinib (BAY2731954) Oral suspension

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Parexel International - Los Angeles
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • PAREXEL International, Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2021
• Primary Completion (Actual): May 20, 2021
• Study Completion (Actual): July 6, 2021

Study Registration Dates

• First Submitted: February 5, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Selitrectinib
• Other Study ID Numbers: 21416

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No