A Study to Assess Absolute Bioavailability (ABA) of Mobocertinib (TAK-788) and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of Carbon-14 ([14C])-Mobocertinib in Male Healthy Participants

NCT ID: NCT03811834

Last Updated: 2024-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-22
• Study Completion Date: 2019-03-11

Brief Summary

The purpose of this study is to determine:

Period 1 (ABA): ABA of mobocertinib following single microdose intravenous administration of 50 microgram (mcg) (approximately 2 microcurie [mcCi]) [14 C]-]-mobocertinib and single oral administration of 160 milligram (mg) mobocertinib.

Period 2 (absorption, distribution, metabolism, and elimination [ADME]): the mass balance and metabolic profile of mobocertinib in plasma, urine, and feces, to characterize the PK of mobocertinib and its metabolites (AP32960 and AP32914) in plasma, whole blood, and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single oral administration of 160 mg (approximately 100 mcCi) [14C]-mobocertinib solution.

Detailed Description

The drug being tested in this study is called mobocertinib. The study will determine ABA of mobocertinib following single microdose of 50 mcg [14C]-mobocertinib and single oral administration of 160 mg mobocertinib and will assess the mass balance and metabolic profile of mobocertinib in plasma, urine, and feces following a single oral administration of 160 mg [14C]-mobocertinib solution, and will characterize the PK of mobocertinib and its metabolites in plasma, whole blood, and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single dose of 160 mg [14C]-mobocertinib.

The study will enroll approximately 6 participants. The study is designed to consist of 2 periods: Period 1 (ABA study period) and Period 2 (ADME study period). In Period 1, all participants will receive single unlabeled oral 160 mg dose of mobocertinib as capsules. At 3.75 hours post oral dosing, participants will receive 15-minute intravenous infusion of a microdose of 50 mcg (approximately 2mcCi) [14C]-mobocertinib. In Period 2, participants will receive single dose of 160 mg (approximately 100 mcCi) [14C]-mobocertinib as an oral solution.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 65 days including screening period. Participants will be contacted approximately 30 days after the last dose of study drug for a follow-up assessment.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg + [14C]-Mobocertinib 160 mg

Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by \[14C\]-mobocertinib 50 mcg (approximately 2 microcurie \[mcCi\]), infusion, intravenously, once on Day 1 of Period 1, further followed by a washout period of 9 days, followed by \[14C\]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.

Group Type: EXPERIMENTAL

Mobocertinib

Intervention Type: DRUG

Mobocertinib capsule, \[14C\]-Mobocertinib intravenous infusion, \[14C\]-Mobocertinib oral solution.

Interventions

Mobocertinib

Mobocertinib capsule, \[14C\]-Mobocertinib intravenous infusion, \[14C\]-Mobocertinib oral solution.

Intervention Type: DRUG

Other Intervention Names

TAK-788

Eligibility Criteria

Inclusion Criteria

1. Continuous non smoker who has not used nicotine containing products for at least 20 years prior to the first dosing and throughout the study, based on subject self-reporting.

2. Body mass index greater than or equal to (>=)18 and less than (˂) 30.0 kilogram per square meter (kg/m^2) at screening.

Exclusion Criteria

1. Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.

2. Has history or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.

3. Has positive urine drug or alcohol results at screening or first check in.

4. Estimated creatinine clearance < 80 milliliter per minute (mL/min) at screening.

5. Has tattoo(s) or scarring at or near the site of intravenous (IV) infusion or any other condition which may interfere with infusion site examination, in the opinion of the investigator.

6. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.

7. Has recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks of first dosing.

8. Has received radiolabeled substances or has been exposed to radiation sources within 12 months of first dosing or is likely to receive radiation exposure or radioisotopes within 12 months of first dosing such that participation in this study would increase their total exposure beyond the recommended levels considered safe (that is., weighted annual limit recommended by the Commission on Radiological Protection [ICRP] of 3000 millirem).

9. Donation of blood or significant blood loss within 56 days prior to the first dosing.

10. Plasma donation within 7 days prior to the first dosing.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Celerion

Lincoln, Nebraska, United States

Countries

United States

References

Hanley MJ, Zhang S, Griffin R, Zhu SX, Fram RJ, Lin J, Venkatakrishnan K, Gupta N. A phase 1 study to assess the absolute bioavailability, mass balance, pharmacokinetics, metabolism, and excretion of [14C]-mobocertinib, an oral inhibitor of EGFR exon 20 insertion mutations, in healthy participants. Invest New Drugs. 2024 Aug;42(4):343-352. doi: 10.1007/s10637-024-01446-y. Epub 2024 May 24.

Reference Type: DERIVED

PMID: 38789848 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1223-7593

Identifier Type: OTHER

Identifier Source: secondary_id

TAK-788-1002

Identifier Type: -

Identifier Source: org_study_id