Phase 1
Completed N=7
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
Healthy Volunteers
Source: ClinicalTrials.gov NCT03811834 ↗
Enrolled (actual)
7
Serious AEs
0.0%
Results posted
Jul 2021
Primary outcomePrimary: Period 1: Percent Absolute Oral Bioavailability (%F) for Mobocertinib — 36.7 percentage bioavailability
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Period 1: Percent Absolute Oral Bioavailability (%F) for Mobocertinib |
36.7 | — |
| PRIMARY Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Urine Relative to the Administered Radioactive Dose |
3.57 | — |
| PRIMARY Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Feces Relative to the Administered Radioactive Dose |
76.0 | — |
| PRIMARY Period 2: Amount of Total Radioactivity Excreted in Urine (Ae[UR]) |
5.777 | — |
| PRIMARY Period 2: Amount of Total Radioactivity Excreted in Feces (Ae[Fe]) |
123.1 | — |
| PRIMARY Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Urine for Mobocertinib |
0.00; 1.061; 0.7462; 0.7364; 0.3443; 0.2173 | — |
| PRIMARY Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Feces for Mobocertinib |
0.00; 16.13; 27.78; 16.10; 4.214; 3.066 | — |
| PRIMARY Period 2, Cmax: Maximum Observed Plasma and Whole Blood Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) |
51.0; 22.7; 4.28; 40.5; 26.7; 3.05 | — |
| PRIMARY Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Mobocertinib and Its Metabolites (AP32960 and AP32914) |
6.00; 4.00; 6.00; 5.01; 5.01; 5.01 | — |
| PRIMARY Period 2: t(1/2): Terminal Disposition Phase Half-life of Mobocertinib and Its Metabolites (AP32960 and AP32914) in Plasma and Whole Blood |
22.8; 30.5; 14.0; 20.5; 30.9; 12.8 | — |
| PRIMARY 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) |
956; 486; 73.4; 729; 556; 52.4 | — |
| PRIMARY 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) |
945; 471; 63.6; 718; 543; 45.7 | — |
| PRIMARY 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) |
944.9; 471.1; 63.61; 717.7; 542.8; 45.74 | — |
| PRIMARY Period 2, Cmax: Maximum Observed Plasma Radioactivity Concentration Equivalents for [14C]-Mobocertinib |
1250 | — |
| PRIMARY Period 2, Cmax: Maximum Observed Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib |
725 | — |
| PRIMARY Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) Equivalents for [14C]-Mobocertinib |
24.0; 24.0 | — |
| PRIMARY Period 2, t(1/2z): Terminal Disposition Phase Half-life of Plasma and Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib |
281; 301 | — |
| PRIMARY Period 2, AUC∞: Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib |
556000 | — |
| PRIMARY Period 2, AUC∞: Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib |
325000 | — |
| PRIMARY Period 2, AUClast: Area Under the Plasma Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]-Mobocertinib |
230300 | — |
| PRIMARY Period 2, AUClast: Area Under the Whole Blood Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]- Mobocertinib |
131000 | — |
| PRIMARY Period 2, AUCt : Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib |
145400 | — |
| PRIMARY Period 2, AUCt : Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib |
70190 | — |
| PRIMARY 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) |
0.001072; 0.1917; 0.2047; 0.1628; 0.05069; 0.02087 | — |
| PRIMARY Period 2, CLR: Renal Clearance for Mobocertinib and Its Metabolites (AP32960 and AP32914) |
0.657; 1.95; 2.85 | — |
| PRIMARY Period 2, Percentage Change of [14C]-Radioactivity in Whole Blood Relative to Plasma Over the Time for [14C]-Mobocertinib, (Whole Blood : Plasma Partitioning Ratio) |
1.022; 0.9851; 0.9055; 0.8403; 0.8221; 0.8545 | — |
| SECONDARY Period 1, Ceoi: Plasma Concentration at the End of Infusion for [14C]-Mobocertinib, and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) |
146.3; 1.842; 2.432 | — |
| SECONDARY Period 1, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration |
56.7; 23.29; 4.086 | — |
| SECONDARY Period 1, Cmax: Maximum Observed Plasma Concentration for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration |
148; 6.631; 3.772 | — |
| SECONDARY 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 |
5.00; 4.502; 5.000; 0.26; 3.257; 2.26 | — |
| SECONDARY 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 |
1050; 478.2; 73.02 | — |
| SECONDARY 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 |
680; 187.8; 89.71 | — |
| SECONDARY 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 |
1032; 461.2; 66.92 | — |
| SECONDARY 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 |
617.9; 133.1; 31.52 | — |
| SECONDARY 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 |
617.9; 133.1; 31.52 | — |
| SECONDARY 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 |
22.9; 29.077; 12.545; 22.2; 20.317; 11.900 | — |
| SECONDARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) |
6; 4 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Laboratory Values |
0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT03811834). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.