Phase 1
Completed N=24
A Study to Evaluate Pharmacokinetics (PK) and Safety of Oral Mobocertinib in Participants With Moderate or Severe Hepatic Impairment (HI) and Normal Hepatic Function
hepatic impairment · Healthy Volunteers
Source: ClinicalTrials.gov NCT04056468 ↗
Enrolled (actual)
24
Serious AEs
0.0%
Results posted
Nov 2023
Primary outcomePrimary: Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) — 9.67; 11.3; 10.5; 3.88 nanograms per milliliter (ng/mL)
Summary
The purpose of this study is to characterize the single-dose plasma PK of mobocertinib and its active metabolites (AP32960 and AP32914) in participants with moderate and/or severe HI compared to matched-healthy participants with normal hepatic function.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
9.67; 11.3; 10.5; 3.88; 2.82; 4.80 | — |
| PRIMARY Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
0.153; 0.167; 0.184; 0.0569; 0.0396; 0.0729 | — |
| PRIMARY AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
206; 291; 199; 91.6; 115; 105 | — |
| PRIMARY AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
3.26; 4.31; 3.50; 1.32; 1.48; 1.60 | — |
| 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) |
192; 275; 186; 69.3; 64.5; 91.9 | — |
| 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) |
3.04; 4.06; 3.28; 1.02; 0.906; 1.40 | — |
| PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
2.00; 4.00; 6.00; 2.00; 4.00; 6.00 | — |
| PRIMARY t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
26.4; 30.7; 22.9; 31.7; 45.0; 25.9 | — |
| PRIMARY λz: Terminal Elimination Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
0.0263; 0.0226; 0.0303; 0.0218; 0.0154; 0.0268 | — |
| PRIMARY CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib |
195; 137; 201 | — |
| PRIMARY CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib |
12300; 9290; 11400 | — |
| PRIMARY Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib |
7400; 6090; 6640 | — |
| PRIMARY Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib |
467000; 412000; 377000 | — |
| SECONDARY Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) |
98.4; 98.5; 98.2; 98.5; 98.6; 98.5 | — |
| SECONDARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) |
1; 0; 2 | — |
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 =60 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) at screening.
Inclusion Criteria for Moderate or Severe HI Participants
- Continuous non-smoker or moderate smoker ( =18.0 and =18.0 and =60 mL/min/1.73 m^2 at screening.
- Chronic HI for at least 3 months before screening, and the HI must be stable, that is, no significant changes in hepatic function in the 30 days preceding screening (or since the last visit if within 6 months before screening) and treatment with stable doses of medication. Has a score on the Child-Pugh Class at screening as follows:
- Moderate HI arm, Child-Pugh Class B: >=7 and =10 and =450 msec in males or >=470 msec in females; Moderate or Severe HI participants: QTcF interval is greater than (>) 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) 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 had significant blood loss within 56 days prior to dosing.
- Plasma donation within 7 days prior to dosing.
- Healthy participants: Positive result at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV); Moderate or Severe HI participants: Positive result at screening for HIV, HBsAg positive participants are allowed to enroll if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is below 1000 copies/milliliter (mL) in the plasma. Participants who are positive for hepatitis C virus antibodies (HCVAb) can be enrolled but must not have detectable HCV ribonucleic acid (RNA) in the plasma.
Data sourced from ClinicalTrials.gov (NCT04056468). 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.