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

• ClinicalTrials.gov Identifier: NCT04771390
• Recruitment Status: Completed
• First Posted: February 25, 2021
• Last Update Posted: August 25, 2021
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

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 (Clinical Trial)
• 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 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: February 16, 2021
• Actual Primary Completion Date: May 20, 2021
• Actual Study Completion Date: July 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 :

1. AUC [ Time Frame: 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

2. AUC(0-24) [ Time Frame: 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

3. Cmax [ Time Frame: 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 :

1. AUC [ Time Frame: 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

2. AUC(0-24) [ Time Frame: 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

3. Cmax [ Time Frame: 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

4. Number of participants with treatment emergent adverse events and severity of treatment emergent adverse events [ Time Frame: Up to 7 weeks ]
   Adverse events that occur or worsen after the first dose of study medication
5. Incidence of laboratory abnormalities, based on clinical safety laboratory assessments [ Time Frame: Up to 7 weeks ]
   Hematology, clinical chemistry and urinalysis test results
6. Ventricular rate [ Time Frame: Up to 7 weeks ]
7. ECG PR interval [ Time Frame: Up to 7 weeks ]
8. ECG QT interval [ Time Frame: Up to 7 weeks ]
9. ECG QRS duration [ Time Frame: Up to 7 weeks ]
10. Blood pressure in mmHg [ Time Frame: Up to 7 weeks ]
11. Heart rate in bpm [ Time Frame: Up to 7 weeks ]
    bpm: beats per minute
12. Body temperature in Celsius [ Time Frame: Up to 7 weeks ]
13. Respiratory rate in breaths/min [ Time Frame: Up to 7 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, California

Parexel International - Los Angeles

Glendale, California, United States, 91206

United States, Maryland

PAREXEL International, Baltimore

Baltimore, Maryland, United States, 21225

Sponsors and Collaborators

Bayer

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT04771390
• Other Study ID Numbers: 21416
• First Posted: February 25, 2021
• Last Update Posted: August 25, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Selitrectinib; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action