A Study to Evaluate Pharmacokinetics (PK) and Safety of Oral Mobocertinib in Participants With Moderate or Severe Hepatic Impairment (HI) and Normal Hepatic Function
Condition: Hepatic Impairment; Healthy Volunteers
MeSH terms: Liver Diseases
Intervention: Mobocertinib
Intervention description: Mobocertinib capsule.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug Therapy

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.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion Criteria for Healthy Participants

          1. Continuous non-smoker or moderate smoker (less than or equal to (<=) 10 cigarettes/day
             or the equivalent) before screening. Participant must agree to consume no more than 5
             cigarettes or equivalent/day from the 7 days prior to mobocertinib dosing and
             throughout the period of PK sample collection.

          2. Body mass index (BMI) greater than or equal to (>=) 18.0 and <=39.0 kilogram per
             square meter (kg/m^2), at screening. Participants will be matched to hepatic impaired
             participants by BMI (mean plus minus [+-] 10%) at screening. At least 50% of the
             participants will be required to be of BMI >=18.0 and <=35.0 kg/m^2, at screening.

          3. Medically healthy with no clinically significant medical history, physical
             examination, laboratory profiles, vital signs or electrocardiograms (ECGs), as deemed
             by the Investigator or designee. Has liver function tests including alanine
             aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP),
             and total bilirubin within the upper limit of normal at screening and at check-in.

          4. Creatinine clearance (estimated glomerular filtration rate [eGFR]) >=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

          1. Continuous non-smoker or moderate smoker (<=10 cigarettes/day or the equivalent)
             before screening. Participant must agree to consume no more than 5 cigarettes or
             equivalent/day from the 7 days prior to mobocertinib dosing and throughout the period
             of pharmacokinetic(s) (PK) sample collection.

          2. BMI >=18.0 and <=39.0 kg/m^2, at screening. At least 50% of the participants will be
             required to be of BMI >=18.0 and <=35.0 kg/m^2, at screening.

          3. Aside from HI, be sufficiently healthy for study participation based upon medical
             history, physical examination, vital signs, ECGs, and screening clinical laboratory
             profiles, as deemed by the Investigator or designee.

          4. Creatinine clearance (eGFR) >=60 mL/min/1.73 m^2 at screening.

          5. 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 <=9.

               -  Severe HI arm, Child-Pugh Class C: >=10 and <=15.

        Exclusion Criteria:

          1. Positive results for COVID-19 at screening or check in.

          2. Seated blood pressure is less than 90/40 millimeters of Mercury (mmHg) or greater than
             150/95 mmHg at screening.

          3. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at
             screening.

          4. Healthy participants: QTcF interval is >=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.

          5. 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.

          6. 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.

          7. Donation of blood or had significant blood loss within 56 days prior to dosing.

          8. Plasma donation within 7 days prior to dosing.

          9. 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.