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

NCT03811834 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-788-1002U1111-1223-7593
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (26)

• Period 1: Percent Absolute Oral Bioavailability (%F) for Mobocertinib

  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.

  Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (14)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

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

EXPERIMENTAL

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

Interventions

Mobocertinib DRUG

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

Also known as: TAK-788

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

Eligibility Criteria

• Age: 19 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.
• Has history or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
• Has positive urine drug or alcohol results at screening or first check in.
• Estimated creatinine clearance \< 80 milliliter per minute (mL/min) at screening.
• 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.
• Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.
• Has recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks of first dosing.
• 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).
• Donation of blood or significant blood loss within 56 days prior to the first dosing.
• Plasma donation within 7 days prior to the first dosing.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

Related Publications (1)

• 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.

  PMID: 38789848 DERIVED

MeSH Terms

Interventions

mobocertinib

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 22, 2019
• Study Start: January 22, 2019
• Primary Completion: March 11, 2019
• Study Completion: March 11, 2019
• Last Updated: February 12, 2024
• Results First Posted: July 30, 2021

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)