Phase 1
Completed N=26
A Study of Mobocertinib Capsules in People With Severe Kidney Problems and People With Healthy Kidneys
Renal impairment · Healthy Volunteers
Source: ClinicalTrials.gov NCT04056455 ↗
Enrolled (actual)
26
Serious AEs
3.9%
Results posted
Jan 2024
Primary outcomePrimary: Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) — 17.1; 11.2; 12.2; 7.92 nanograms per milliliter(ng/mL)
Summary
It is hoped that mobocertinib will eventually help people with cancer with severely reduced kidney function. The main aim of this study is to learn about the levels of mobocertinib in the blood and urine of participants with severely reduced kidney function and participants with healthy kidneys. These participants do not have cancer. The information from this study will be used to work out the best dose of mobocertinib for people with cancer with severely reduced kidney function in the future.
At the first visit, the study doctor will check who can take part. Participants who can take part will be placed into 1 of 2 treatment groups. Participants with severely reduced kidney function will be in 1 group. Participants with healthy kidneys will be in the other group. Participants in both groups will receive the same treatment and the group results will be compared.
Participants from both groups will take 1 capsule of mobocertinib. They will stay in the clinic for 10 days so the study doctors can check the amount of mobocertinib in the blood and urine of these participants over time. The study doctors will also check if the participants have any side effects from this treatment.
The clinic will call the participants 30 days after they took mobocertinib to check if they have any more side effects from their treatment.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
17.1; 11.2; 12.2; 7.92; 2.24; 1.51 | — |
| PRIMARY Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
0.188; 0.137; 0.149; 0.0904; 0.0112; 0.0144 | — |
| PRIMARY AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
720; 255; 328; 184; 93.6; 42.3 | — |
| PRIMARY AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
7.61; 3.16; 4.00; 2.15; 0.469; 0.461 | — |
| PRIMARY AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
463; 219; 305; 159; 43.8; 18.7 | — |
| PRIMARY AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
5.10; 2.68; 3.72; 1.82; 0.219; 0.172 | — |
| PRIMARY Combined Molar Cmax,u: Combined Molar Unbound Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
0.708; 0.419 | — |
| PRIMARY Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
16.9; 8.14 | — |
| PRIMARY Combined Molar AUCinf,u: Combined Molar Unbound AUCinf for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
30.1; 16.8 | — |
| PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
6.00; 6.00; 4.00; 6.00; 6.00; 6.00 | — |
| PRIMARY t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
28.0; 23.2; 40.1; 31.7; 20.6; 14.6 | — |
| PRIMARY λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
0.0248; 0.0299; 0.0173; 0.0219; 0.0336; 0.0475 | — |
| PRIMARY CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib |
111; 314 | — |
| PRIMARY CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib |
10500; 25300 | — |
| PRIMARY Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib |
4480; 10500 | — |
| PRIMARY Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib |
424000; 847000 | — |
| PRIMARY CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine |
0.271; 0.357; 0.108; 0.296; 0.0360; 0.0895 | — |
| PRIMARY Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine |
0.339; 0.446 | — |
| PRIMARY CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
0.694; 1.78; 0.373; 1.77; 0.683; 3.11 | — |
| SECONDARY Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
98.8; 98.7; 98.7; 98.8; 99.3; 99.2 | — |
| SECONDARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) |
5; 0 | — |
Eligibility Criteria
Inclusion Criteria
Inclusion Criteria for Healthy Participants:
- Continuous non-smoker or moderate smoker (less than or equal to [ =) 18.0 and =18.0 and =90 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) based on the Modification of Diet in Renal Disease (MDRD) equation at screening divided by standard body surface area (BSA) value of 1.73 m^2. For participants with non-standard BSA, the eGFR value calculated by MDRD formula will be multiplied by the individual's BSA calculated using appropriate formula and divided by 1.73 m^2.
Inclusion Criteria for Participants with RI:
- Continuous non-smoker or moderate smoker ( =18.0 and =18.0 and ] 6 months), stable (no significant changes in renal function [less than [ =450 millisecond (msec) in males or >=470 msec in females or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening
- RI participants: QTcF interval is >500 msec or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening.
- Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements) as indicated in (Prohibitions and Concomitant Medication) for the prohibited time period.
- Been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to dosing and throughout the study.
- Donation of blood or significant blood loss within 56 days prior to dosing.
- Plasma donation within 7 days prior to dosing.
Data sourced from ClinicalTrials.gov (NCT04056455). 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.