Key Inclusion Criteria:  Healthy, adult, male or female (of non-childbearing potential only), 18-55 years of age. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilogram per meter square (kg/m^2) at screening, and a minimum weight of 50.0 kg and a maximum weight of 100.0 kg at screening. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study. Medically healthy with no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs, and laboratory evaluations. Female must be of non-childbearing potential only and must have undergone a sterilization procedure at least 6 months prior to the first dosing, or Postmenopausal women should have amenorrhea for at least 1 year prior to the first dosing. A non-vasectomized male participant must agree to use a highly effective method of birth control with female partners of childbearing potential or with pregnant partners during the study and for 120 days following last dosing. Able to comprehend and willing to sign an Informed Consent Form (ICF) and abide by the clinical protocol, study procedures, and restrictions. For Part 1 only: Participant must be a CYP2D6 extensive metabolizer or CYP2D6 poor metabolizer as determined by a valid genotyping method. For Part 2 only: Participant must not be a CYP2C9 and CYP2C19 poor metabolizer as determined by a valid genotyping method and must be a CYP2D6 extensive metabolizer as determined by a valid genotyping method. For Part 3 only: Participant must be a CYP2D6 extensive metabolizer as determined by a valid genotyping method.  Key Exclusion Criteria:  Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the PI (or designee). History of a developing or established acute event or infection in the prior 2 weeks to screening. History of significant hypersensitivity, or idiosyncratic reaction to poziotinib, itraconazole, phenytoin, paroxetine, or related drugs, food, or other substances. Any surgical or medical condition within 6 months prior to first dosing that may potentially alter absorption, distribution, metabolism or excretion of the study drugs, in the opinion of the PI (or designee). History or presence of alcoholism or drug/chemical abuse within 2 years prior to check-in. Female participants with a positive pregnancy test result or lactating. Positive urine drug or alcohol test results at screening or check-in. Positive hepatitis panel (hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) and/or positive human immunodeficiency virus (HIV) test at screening. Automatic reflex Differential and ribonucleic acid testing will be conducted in the event of a reactive antibody/antigen screen. Seated blood pressure is less than 90/40 millimetre of mercury (mmHg) or greater than 140/90 mmHg at screening. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening. QT interval with Fridericia's correction (QTcF) interval is >450 millisecond (msec) (males) or >470 msec (females).  Unable to refrain from or anticipates the use of:  Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing and throughout the study. Hormone replacement therapy will not be allowed. Any drugs known to be inhibitors and/or inducers of CYP3A, CYP2D6, CYP2C9, or CYP2C19 enzymes; and/or P-gp; and/or gastric acid reducing agents (proton-pump inhibitors, H2-receptor antagonists, antacids) for 28 days prior to the first dosing and throughout the study (except those required as part of the study). Has a coagulation test (i.e., prothrombin time and activated partial thromboplastin time) outside of normal ranges at screening or at check-in. Has platelet, hemoglobin, or hematocrit that are below the lower limit of normal at screening or at check-in. Has alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin that are greater than the upper limit of normal at screening or at check-in. Estimated creatinine clearance <90 milliliter per minute (mL/min) at screening. Participation in another clinical study within 30 days prior to the first dosing. Prior exposure to poziotinib.  For Part 1 Only:History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and as confirmed by the Sponsor:  Ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, family history of Long QT Syndrome). Uncorrected hypokalemia (potassium levels < 3.7) and/or hypomagnesemia (magnesium levels < 1.9). Myasthenia gravis. For Part 2 Only: History of seizure (excluding simple febrile seizure), epilepsy, severe head injury, multiple sclerosis, or other known neurological conditions which the Investigator considers to be clinically significant.  Is at suicidal risk in the opinion of the PI as per the following criteria:  Any suicidal attempts within 12 months prior to screening. any suicidal intent including a plan or C-SSRS answer of "YES" on suicidal ideation currently or within 3 months.