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

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03811834
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 1.6
• Patients Per Site Per Month: 4.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Mobocertinib	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1 Study to Assess Absolute Bioavailability of TAK-788 and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-788 in Male Healthy Subjects
• Actual Study Start Date: Jan 22, 2019
• Actual Primary Completion Date: Mar 11, 2019
• Actual Study Completion Date: Mar 11, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: Mobocertinib; Mobocertinib capsule, [14C]-Mobocertinib intravenous infusion, [14C]-Mobocertinib oral solution.; Other Names: TAK-788

Outcome Measures

Primary Outcome Measures

1. Period 1: Percent Absolute Oral Bioavailability (%F) for Mobocertinib [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

   Absolute bioavailability (F), defined as the fraction or percentage of the unchanged, orally administered dose that is systemically available, relative to the total dose administered intravenously. Percent Absolute Oral Bioavailability (%F) was calculated as dose of [14C]-mobocertinib intravenous in mg*AUC∞ of mobocertinib (oral)/dose of mobocertinib (oral)* AUC∞ of [14C]-mobocertinib (intravenous)*100.

2. Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Urine Relative to the Administered Radioactive Dose [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

3. Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Feces Relative to the Administered Radioactive Dose [Day 1 pre-dose and at multiple time points (up to 432 hours) post-dose]

4. Period 2: Amount of Total Radioactivity Excreted in Urine (Ae[UR]) [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

5. Period 2: Amount of Total Radioactivity Excreted in Feces (Ae[Fe]) [Day 1 pre-dose and at multiple time points (up to 432 hours) post-dose]

6. Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Urine for Mobocertinib [Day 1: Pre-dose, 0-12 hours (hrs), 12-24 hrs, 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs, 216-240 hrs post-dose]

7. Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Feces for Mobocertinib [Day 1: at Pre-dose, 0-24 hours (hrs), 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs, 216-240 hrs; 240-264 hrs, 264-288 hrs, 288-312 hrs, 213-408 hrs and 408-432 hrs]

8. Period 2, Cmax: Maximum Observed Plasma and Whole Blood Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

9. Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Mobocertinib and Its Metabolites (AP32960 and AP32914) [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

10. Period 2: t(1/2): Terminal Disposition Phase Half-life of Mobocertinib and Its Metabolites (AP32960 and AP32914) in Plasma and Whole Blood [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

11. Period 2, AUC∞: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Metabolites (AP32960 and AP32914) [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

12. Period 2, AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) [Day 1 pre-dose at multiple time points (up to 240 hours) post-dose]

13. Period 2, AUCt: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time t for Mobocertinib and Its Metabolites (AP32960 and AP32914) [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

14. Period 2, Cmax: Maximum Observed Plasma Radioactivity Concentration Equivalents for [14C]-Mobocertinib [Day 1 pre-dose at multiple time points (up to 240 hours) post-dose]

15. Period 2, Cmax: Maximum Observed Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib [Day 1 pre-dose at multiple time points (up to 240 hours) post-dose]

16. Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) Equivalents for [14C]-Mobocertinib [Day 1 pre-dose at multiple time points (up to 240 hours) post-dose]

17. Period 2, t(1/2z): Terminal Disposition Phase Half-life of Plasma and Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib [Day 1 pre-dose at multiple time points (up to 240 hours) post-dose]

18. Period 2, AUC∞: Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

19. Period 2, AUC∞: Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

20. Period 2, AUClast: Area Under the Plasma Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]-Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

21. Period 2, AUClast: Area Under the Whole Blood Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]- Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

22. Period 2, AUCt : Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

23. Period 2, AUCt : Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

24. Period 2, Aet1-t2: Amount of Unchanged Drug Excreted in the Urine in Each Collection Interval From t1 to t2 for Mobocertinib and Its Metabolites (AP32960 and AP32914) [Day 1: at Pre-dose, 0-12 hours (hrs), 12-24 hrs, 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs and 216-240 hrs post dose]

25. Period 2, CLR: Renal Clearance for Mobocertinib and Its Metabolites (AP32960 and AP32914) [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

26. Period 2, Percentage Change of [14C]-Radioactivity in Whole Blood Relative to Plasma Over the Time for [14C]-Mobocertinib, (Whole Blood : Plasma Partitioning Ratio) [At 0.5 hours (hrs), 1 hr, 2 hrs, 3 hrs, 4 hrs, 5 hrs, 6 hrs, 8 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs, 144 hrs, 168 hrs, 192 hrs, 216 hrs and 240 hrs post-dose]

Secondary Outcome Measures

1. Period 1, Ceoi: Plasma Concentration at the End of Infusion for [14C]-Mobocertinib, and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

2. Period 1, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

3. Period 1, Cmax: Maximum Observed Plasma Concentration for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

4. Period 1, Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral, and [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

   Data for mobocertinib and its metabolites (AP32960 and AP32914) is reported following the oral administration, and data for [14C]-mobocertinib and its metabolites ([14C]-AP32960 and [14C]-AP32914) is reported following intravenous administration.

5. Period 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

6. Period 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]-Mobocertinib and Its Metabolites ( [14C]-AP32960 and [14C]-AP32914) After Intravenous Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

7. Period 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

8. Period 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

9. Period 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

10. Period 1, t(1/2):Terminal Disposition Phase Half-Life of Mobocertinib and Its Metabolites (AP32960 and AP32914) in Plasma After Oral, and [14C]-Mobocertinib and Its Metabolites ( [14C]-AP32960 and [14C]-AP32914) in Plasma After Intravenous Administration [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

    Data for mobocertinib and its metabolites (AP32960 and AP32914) is reported following the oral administration, and data for [14C]-mobocertinib and its metabolites ([14C]-AP32960 and [14C]-AP32914) is reported following intravenous administration.

11. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)]

12. Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings [Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)]

13. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)]

14. Number of Participants With Clinically Significant Change From Baseline in Laboratory Values [Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Lincoln	Nebraska	United States	68502

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Feb 27, 2019
• Statistical Analysis Plan - Aug 8, 2019

More Information

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03811834
• Other Study ID Numbers: TAK-788-1002; U1111-1223-7593
• First Posted: Jan 22, 2019
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Millennium Pharmaceuticals, Inc.: Drug Therapy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 22 January 2019 to 11 March 2019.
Pre-assignment Detail	Healthy male participants were enrolled in this 2-period study to receive mobocertinib 160 milligram (mg), capsules followed by carbon-14 [14C]-mobocertinib 50 microgram (mcg), infusion in Period 1 (Absolute Bioavailability [ABA]) and [14C]-mobocertinib 160 mg, solution in Period 2 (Absorption, Distribution, Metabolism, and Elimination [ADME]).

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg + [14C]-Mobocertinib 160 mg
Arm/Group Description	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.
Period Title: Period 1 ( 7 Days)
STARTED	7
COMPLETED	6
NOT COMPLETED	1
Period Title: Period 1 ( 7 Days)
STARTED	6
COMPLETED	6
NOT COMPLETED	0
Period Title: Period 1 ( 7 Days)
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg +[14C]-Mobocertinib 160 mg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 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.
Overall Participants	7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.6 (12.75)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	7 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 28.6%
Not Hispanic or Latino	5 71.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	1 14.3%
Black or African American	1 14.3%
White	5 71.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%
Weight (kilogram (Kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (Kg)]	83.74 (6.141)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	175.9 (4.14)
Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	27.079 (1.6520)

Outcome Measures

1. Primary Outcome

Title	Period 1: Percent Absolute Oral Bioavailability (%F) for Mobocertinib
Description	Absolute bioavailability (F), defined as the fraction or percentage of the unchanged, orally administered dose that is systemically available, relative to the total dose administered intravenously. Percent Absolute Oral Bioavailability (%F) was calculated as dose of [14C]-mobocertinib intravenous in mg*AUC∞ of mobocertinib (oral)/dose of mobocertinib (oral)* AUC∞ of [14C]-mobocertinib (intravenous)*100.
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This outcome measure (OM) was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
Geometric Mean (90% Confidence Interval) [percentage bioavailability]	36.7

2. Primary Outcome

Title	Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Urine Relative to the Administered Radioactive Dose
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percentage of radioactive dose]	3.57 (12.6)

3. Primary Outcome

Title	Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Feces Relative to the Administered Radioactive Dose
Time Frame	Day 1 pre-dose and at multiple time points (up to 432 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [percentage of radioactive dose]	76.0 (6.5)

4. Primary Outcome

Title	Period 2: Amount of Total Radioactivity Excreted in Urine (Ae[UR])
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [milligram equivalent (mg eq)]	5.777 (12.6)

5. Primary Outcome

Title	Period 2: Amount of Total Radioactivity Excreted in Feces (Ae[Fe])
Time Frame	Day 1 pre-dose and at multiple time points (up to 432 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [mg eq]	123.1 (6.1)

6. Primary Outcome

Title	Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Urine for Mobocertinib
Time Frame	Day 1: Pre-dose, 0-12 hours (hrs), 12-24 hrs, 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs, 216-240 hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Pre-dose	0.00 (0.00)
0-12 hours	1.061 (0.22924)
12-24 hours	0.7462 (0.15716)
24-48 hours	0.7364 (0.12118)
48-72 hours	0.3443 (0.051037)
72-96 hours	0.2173 (0.040842)
96-120 hours	0.1425 (0.027883)
120-144 hours	0.1050 (0.021753)
144-168 hours	0.07582 (0.041180)
168-192 hours	0.07517 (0.012835)
192-216 hours	0.05243 (0.029772)
216-240 hours	0.05137 (0.029359)

7. Primary Outcome

Title	Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Feces for Mobocertinib
Time Frame	Day 1: at Pre-dose, 0-24 hours (hrs), 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs, 216-240 hrs; 240-264 hrs, 264-288 hrs, 288-312 hrs, 213-408 hrs and 408-432 hrs

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Pre-dose	0.00 (0.00)
0-24 hours	16.13 (16.772)
24-48 hours	27.78 (19.584)
48-72 hours	16.10 (21.089)
72-96 hours	4.214 (5.3488)
96-120 hours	3.066 (2.8311)
120-144 hours	1.638 (1.8080)
144-168 hours	2.756 (3.3943)
168-192 hours	0.9919 (0.83406)
192-216 hours	2.069 (1.0034)
216-240 hours	1.695 (1.1513)
240-264 hours	0.1056 (0.14927)
264-288 hours	0.2216 (0.31341)
288-312 hours	0.7632 (NA)
312-408 hours	0.3107 (NA)
408-432 hours	0.1143 (NA)

8. Primary Outcome

Title	Period 2, Cmax: Maximum Observed Plasma and Whole Blood Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914)
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma: Mobocertinib	51.0 (34.9)
Plasma: AP32960	22.7 (19.8)
Plasma: AP32914	4.28 (34.7)
Whole Blood: Mobocertinib	40.5 (29.1)
Whole Blood: AP32960	26.7 (10.6)
Whole Blood: AP32914	3.05 (28.6)

9. Primary Outcome

Title	Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Mobocertinib and Its Metabolites (AP32960 and AP32914)
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma: Mobocertinib	6.00
Plasma: AP32960	4.00
Plasma: AP32914	6.00
Whole Blood: Mobocertinib	5.01
Whole Blood: AP32960	5.01
Whole Blood: AP32914	5.01

10. Primary Outcome

Title	Period 2: t(1/2): Terminal Disposition Phase Half-life of Mobocertinib and Its Metabolites (AP32960 and AP32914) in Plasma and Whole Blood
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma: Mobocertinib	22.8 (26.6)
Plasma: AP32960	30.5 (21.1)
Plasma: AP32914	14.0 (30.6)
Whole Blood: Mobocertinib	20.5 (25.4)
Whole Blood: AP32960	30.9 (12.1)
Whole Blood: AP32914	12.8 (23.1)

11. Primary Outcome

Title	Period 2, AUC∞: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Metabolites (AP32960 and AP32914)
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma: Mobocertinib	956 (38.6)
Plasma: AP32960	486 (26.7)
Plasma: AP32914	73.4 (39.9)
Whole Blood: Mobocertinib	729 (32.8)
Whole Blood: AP32960	556 (20.2)
Whole Blood: AP32914	52.4 (37.3)

12. Primary Outcome

Title	Period 2, AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914)
Time Frame	Day 1 pre-dose at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma: Mobocertinib	945 (39.2)
Plasma: AP32960	471 (27.5)
Plasma: AP32914	63.6 (45.7)
Whole Blood: Mobocertinib	718 (33.2)
Whole Blood: AP32960	543 (20.5)
Whole Blood: AP32914	45.7 (40.4)

13. Primary Outcome

Title	Period 2, AUCt: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time t for Mobocertinib and Its Metabolites (AP32960 and AP32914)
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma: Mobocertinib	944.9 (39.2)
Plasma: AP32960	471.1 (27.5)
Plasma: AP32914	63.61 (45.7)
Whole Blood: Mobocertinib	717.7 (33.2)
Whole Blood: AP32960	542.8 (20.5)
Whole Blood: AP32914	45.74 (40.4)

14. Primary Outcome

Title	Period 2, Cmax: Maximum Observed Plasma Radioactivity Concentration Equivalents for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent/milliliter(ng eq/mL)]	1250 (13.4)

15. Primary Outcome

Title	Period 2, Cmax: Maximum Observed Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent/ gram (ng eq/g)]	725 (14.6)

16. Primary Outcome

Title	Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) Equivalents for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-Mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma	24.0
Whole Blood	24.0

17. Primary Outcome

Title	Period 2, t(1/2z): Terminal Disposition Phase Half-life of Plasma and Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Plasma	281 (29.1)
Whole Blood	301 (28.1)

18. Primary Outcome

Title	Period 2, AUC∞: Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent*hour per milliliter]	556000 (14.9)

19. Primary Outcome

Title	Period 2, AUC∞: Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent*hour per gram]	325000 (21.2)

20. Primary Outcome

Title	Period 2, AUClast: Area Under the Plasma Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent*hour per milliliter]	230300 (15.5)

21. Primary Outcome

Title	Period 2, AUClast: Area Under the Whole Blood Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]- Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent*hour per gram]	131000 (18.5)

22. Primary Outcome

Title	Period 2, AUCt : Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent*hour per milliliter]	145400 (35.3)

23. Primary Outcome

Title	Period 2, AUCt : Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalent*hour per gram]	70190 (32.4)

24. Primary Outcome

Title	Period 2, Aet1-t2: Amount of Unchanged Drug Excreted in the Urine in Each Collection Interval From t1 to t2 for Mobocertinib and Its Metabolites (AP32960 and AP32914)
Time Frame	Day 1: at Pre-dose, 0-12 hours (hrs), 12-24 hrs, 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs and 216-240 hrs post dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Mobocertinib: Pre-dose	0.001072 (0.0010474)
Mobocertinib: 0 to 12 hours	0.1917 (0.10878)
Mobocertinib: 12 to 24 hours	0.2047 (0.084347)
Mobocertinib: 24 to 48 hours	0.1628 (0.050589)
Mobocertinib: 48 to 72 hours	0.05069 (0.029114)
Mobocertinib: 72 to 96 hours	0.02087 (0.013052)
Mobocertinib: 96 to 120 hours	0.01028 (0.0052244)
Mobocertinib: 120 to 144 hours	0.005860 (0.0055472)
Mobocertinib: 144 to 168 hours	0.002438 (0.0014131)
Mobocertinib: 168 to 192 hours	0.0009682 (0.0011637)
Mobocertinib: 192 to 216 hours	0.0009890 (0.00090295)
Mobocertinib: 216 to 240 hours	0.0002824 (0.00063158)
AP32960: Pre-dose	0.005308 (0.0045461)
AP32960: 0-12 hours	0.2948 (0.078117)
AP32960: 12-24 hours	0.2199 (0.056834)
AP32960: 24-48 hours	0.2166 (0.049030)
AP32960: 48-72 hours	0.09444 (0.020647)
AP32960: 72-96 hours	0.05401 (0.014311)
AP32960: 96-120 hours	0.03017 (0.0070669)
AP32960: 120-144 hours	0.01764 (0.0068670)
AP32960: 144-168 hours	0.01082 (0.0028229)
AP32960: 168-192 hours	0.007272 (0.0023649)
AP32960: 192-216 hours	0.005427 (0.0021935)
AP32960: 216-240 hours	0.004235 (0.0016891)
AP32914: Pre-dose	0.00 (0.00)
AP32914: 0-12 hours	0.08336 (0.022896)
AP32914: 12-24 hours	0.06029 (0.015305)
AP32914: 24-48 hours	0.04953 (0.021338)
AP32914: 48-72 hours	0.01543 (0.0068257)
AP32914: 72-96 hours	0.005859 (0.0040117)
AP32914: 96-120 hours	0.002477 (0.0016606)
AP32914: 120-144 hours	0.0008353 (0.0010134)
AP32914: 144-168 hours	0.0001780 (0.00043613)
AP32914: 168-192 hours	0.00 (0.00)
AP32914: 192-216 hours	0.00 (0.00)
AP32914: 216-240 hours	0.00 (0.00)

25. Primary Outcome

Title	Period 2, CLR: Renal Clearance for Mobocertinib and Its Metabolites (AP32960 and AP32914)
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
Mobocertinib	0.657 (44.3)
AP32960	1.95 (22.5)
AP32914	2.85 (27.9)

26. Primary Outcome

Title	Period 2, Percentage Change of [14C]-Radioactivity in Whole Blood Relative to Plasma Over the Time for [14C]-Mobocertinib, (Whole Blood : Plasma Partitioning Ratio)
Time Frame	At 0.5 hours (hrs), 1 hr, 2 hrs, 3 hrs, 4 hrs, 5 hrs, 6 hrs, 8 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs, 144 hrs, 168 hrs, 192 hrs, 216 hrs and 240 hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time points. This OM was planned to be assessed only in Period 2.

Arm/Group Title	[14C]-Mobocertinib 160 mg
Arm/Group Description	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	6
At 0.5 hour	1.022 (21.9)
At 1 hour	0.9851 (36.0)
At 2 hours	0.9055 (25.3)
At 3 hours	0.8403 (22.4)
At 4 hours	0.8221 (23.3)
At 5 hours	0.8545 (17.2)
At 6 hours	0.7647 (18.6)
At 8 hours	0.7634 (20.7)
At 12 hours	0.7573 (17.6)
At 24 hours	0.8139 (23.0)
At 36 hours	0.7028 (13.2)
At 48 hours	0.7113 (14.7)
At 72 hours	0.6453 (18.8)
At 96 hours	0.6164 (18.0)
At 120 hours	0.6260 (13.2)
At 144 hours	0.5946 (NA)

27. Secondary Outcome

Title	Period 1, Ceoi: Plasma Concentration at the End of Infusion for [14C]-Mobocertinib, and Its Metabolites ([14C]-AP32960 and [14C]-AP32914)
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously over 15 minutes, once on Day 1 of Period 1.
Measure Participants	6
[14C]-Mobocertinib	146.3 (46.4)
[14C]- AP32960	1.842 (20.5)
[14C]- AP32914	2.432 (9.3)

28. Secondary Outcome

Title	Period 1, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
Mobocertinib	56.7 (52.2)
AP32960	23.29 (21.2)
AP32914	4.086 (36.0)

29. Secondary Outcome

Title	Period 1, Cmax: Maximum Observed Plasma Concentration for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
[14C]-mobocertinib	148 (44.0)
[14C]-AP32960	6.631 (76.4)
[14C]-AP32914	3.772 (33.8)

30. Secondary Outcome

Title	Period 1, Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral, and [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration
Description	Data for mobocertinib and its metabolites (AP32960 and AP32914) is reported following the oral administration, and data for [14C]-mobocertinib and its metabolites ([14C]-AP32960 and [14C]-AP32914) is reported following intravenous administration.
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
Mobocertinib	5.00
AP32960	4.502
AP32914	5.000
[14C]-mobocertinib	0.26
[14C]- AP32960	3.257
[14C]- AP32914	2.26

31. Secondary Outcome

Title	Period 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
Mobocertinib	1050 (64.9)
AP32960	478.2 (30.6)
AP32914	73.02 (53.2)

32. Secondary Outcome

Title	Period 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]-Mobocertinib and Its Metabolites ( [14C]-AP32960 and [14C]-AP32914) After Intravenous Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
[14C]-Mobocertinib	680 (30.4)
[14C]- AP32960	187.8 (60.2)
[14C]- AP32914	89.71 (NA)

33. Secondary Outcome

Title	Period 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
Mobocertinib	1032 (65.6)
AP32960	461.2 (30.1)
AP32914	66.92 (53.6)

34. Secondary Outcome

Title	Period 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
[14C]-Mobocertinib	617.9 (34.0)
[14C]-AP32960	133.1 (63.1)
[14C]-AP32914	31.52 (113.7)

35. Secondary Outcome

Title	Period 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
[14C]-Mobocertinib	617.9 (34.0)
[14C]- AP32960	133.1 (63.1)
[14C]- AP32914	31.52 (113.7)

36. Secondary Outcome

Title	Period 1, t(1/2):Terminal Disposition Phase Half-Life of Mobocertinib and Its Metabolites (AP32960 and AP32914) in Plasma After Oral, and [14C]-Mobocertinib and Its Metabolites ( [14C]-AP32960 and [14C]-AP32914) in Plasma After Intravenous Administration
Description	Data for mobocertinib and its metabolites (AP32960 and AP32914) is reported following the oral administration, and data for [14C]-mobocertinib and its metabolites ([14C]-AP32960 and [14C]-AP32914) is reported following intravenous administration.
Time Frame	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given timepoints. This OM was planned to be assessed only in Period 1.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.
Measure Participants	6
Mobocertinib	22.9 (17.9)
AP32960	29.077 (18.2)
AP32914	12.545 (37.5)
[14C]-Mobocertinib	22.2 (41.3)
[14C]- AP32960	20.317 (39.1)
[14C]- AP32914	11.900 (NA)

37. Secondary Outcome

Title	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time Frame	Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least one dose of study drug.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg	[14C]-Mobocertinib 160 mg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	7	6
Count of Participants [Participants]	6 85.7%	4 NaN

38. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
Time Frame	Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least one dose of study drug.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg	[14C]-Mobocertinib 160 mg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	7	6
Count of Participants [Participants]	0 0%	0 NaN

39. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame	Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least one dose of study drug.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg	[14C]-Mobocertinib 160 mg
Arm/Group Description	Mobocertinib160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	7	6
Count of Participants [Participants]	0 0%	0 NaN

40. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Time Frame	Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least one dose of study drug.

Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg	[14C]-Mobocertinib 160 mg
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.	[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
Measure Participants	7	6
Count of Participants [Participants]	0 0%	0 NaN

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 30 days after last dose of study drug in Period 2 (up to Day 41)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg		[14C]-Mobocertinib 160 mg
Arm/Group Description	Mobocertinib160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 mcCi), infusion, intravenously, once on Day 1 of Period 1.		[14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.
All Cause Mortality
	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg		[14C]-Mobocertinib 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/6 (0%)
Serious Adverse Events
	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg		[14C]-Mobocertinib 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg		[14C]-Mobocertinib 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)		4/6 (66.7%)
Gastrointestinal disorders
Constipation	1/7 (14.3%)		1/6 (16.7%)
Diarrhoea	1/7 (14.3%)		1/6 (16.7%)
Eructation	1/7 (14.3%)		0/6 (0%)
Faeces discoloured	0/7 (0%)		1/6 (16.7%)
Haematochezia	0/7 (0%)		1/6 (16.7%)
Nausea	2/7 (28.6%)		0/6 (0%)
Salivary hypersecretion	1/7 (14.3%)		0/6 (0%)
Vomiting	1/7 (14.3%)		0/6 (0%)
General disorders
Chest discomfort	0/7 (0%)		1/6 (16.7%)
Injury, poisoning and procedural complications
Contusion	1/7 (14.3%)		0/6 (0%)
Metabolism and nutrition disorders
Cow's milk intolerance	0/7 (0%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/7 (14.3%)		0/6 (0%)
Nervous system disorders
Headache	0/7 (0%)		1/6 (16.7%)
Psychiatric disorders
Insomnia	0/7 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/7 (0%)		1/6 (16.7%)
Rhinorrhoea	1/7 (14.3%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.