| Eligibility |
Inclusion Criteria:
- Healthy subjects aging 18 to 55 years with Body mass index (BMI) 18.0 to 30.0 kg/m2.
- Weight : = 55 kg for males and = 45 kg for females.
- Healthy status as defined by the absence of evidence of any clinically significant, in
the opinion of the Investigator, active or chronic disease following a detailed
medical and surgical history, a complete physical examination.
- Ability and willingness to abstain from alcohol-, caffeine-, and
methylxanthine-containing beverages or food during the stay in study center.
- No clinically significant hematological or coagulation abnormalities, as judged by the
Investigator.
- Male subjects and female subjects of childbearing potential must agree to use
protocol-specified method(s) of contraception and comply with pregnancy precautions.
- All nonregular medication (including over-the-counter [OTC] medication, health
supplements, and herbal remedies such as St. John's wort extract) must have been
stopped at least 14 days or 5 half-lives, if known (whichever is longer) prior to the
admission to the clinical research center.
- Normal baseline pulmonary function tests (= 80% predicted normal for spirometry, lung
volumes).
- Normal baseline ECG (QTcF < 450 msec, PR < 220 msec).
- Adequate organ function including hepatic, renal, cardiac, and bone marrow function,
as determined by the Investigator.
Exclusion Criteria:
- Employee of PRA or the Sponsor.
- Any condition which, in the opinion of the Investigator, would interfere with the
subject's ability to provide informed consent, comply with study instructions,
confound interpretation of study results, or endanger the subject if he or she takes
part in the trial.
- Women who are pregnant, lactating, or planning to attempt to become pregnant during
this study or within 30 days after dosing of study drug.
- For all females of childbearing potential: positive pregnancy test at screening and at
admission to the clinic.
- Males with female partners who are pregnant, lactating, or planning to attempt to
become pregnant during this study or within 90 days after dosing of study drug.
- Use of any investigational drug or device within 30 days of the first dose of study
drug.
- Any disease which, in the opinion of the Investigator, poses an unacceptable risk to
the subjects.
- Clinically relevant issues of visual function as determined from the medical history
and physical exams, as judged by the Investigator.
- Clinically significant history of any drug sensitivity, drug allergy, or food allergy,
as determined by the Investigator (such as anaphylaxis, hepatotoxicity, or treatment
with steroids or epinephrine). Confirmatory circumstances would include treatment with
epinephrine or in Emergency Department.
- History of allergy or hypersensitivity to DZD9008, or other drugs similar in class
(EGFR/HER2/BTK inhibitor) or similar in chemical structure to DZD9008, as judged by
the Investigator.
- History of major surgery or blood transfusion within 30 days prior to the first drug
administration.
- History of malignancy of any type, except for the following: surgically excised
non-melanomatous skin cancers more than 5 years prior to receiving the investigational
medicinal product.
- Evidence of clinically significant or relevant renal, hematological, endocrine,
pulmonary, GI, cardiovascular, hepatic, psychiatric, neurological, or allergic
disease, as judged by the Investigator.
- Manifestation of malabsorption due to prior GI surgery, GI disease, or any other
reason that may affect the absorption of DZD9008.
- Positive result from a COVID-19 test per local policy and requirement.
- Positive test result for alcohol and/or drugs of abuse at screening or on Day1.
- Positive test result from Quantiferon-TB Gold test.
- Presence of pulmonary infections or other clinically significant active infection
within 30 days of informed consent.
- Received COVID-19 vaccine or any live vaccine within 4 weeks prior to the first dose
of the investigational medicinal product.
- Self-reported substance abuse (eg, alcohol, licit, or illict drugs) within 12 months
of screening.
- Using tobacco or nicotine products within 90 days prior to the first drug
administration.
- Strenuous activity, sunbathing, and contact sports within 48 hours (2 days) prior to
admission to the clinical facility through follow-up.
- History of donation of more than 500 mL of blood within 60 days prior to dosing in the
clinical research center or planned donation before 30 days has elapsed since intake
of study drug.
- Plasma or platelet donation within 7 days of dosing and through follow-up.
- History within the previous 12 months of alcohol consumption exceeding 2 standard
drinks per day on average (1 standard drink=12 oz beer, 5 oz wine, and 1.5 oz
spirits). Alcohol consumption will be prohibited 72 hours prior to admission to the
clinical facility and until discharge in the last study period.
- Positive screening test for hepatitis B surface antigen (HBsAg), hepatitis C virus
(HCV) antibodies, or HIV 1 and 2 antibodies.
- Consumption of any nutrients known to modulate CYP450 enzymes activity (eg, grapefruit
or grapefruit juice, pomelo juice, star fruit, or Seville [blood] orange products)
within 14 days prior to administration of study drug and during the study (until after
discharge in the last study period).
- Abnormal echocardiogram (ECHO) at baseline (eg, left ventricular ejection fraction
[LVEF] < 50%), as judged by the Investigator.
- History of allergy, severe adverse reaction, intolerance, or hypersensitivity to
itraconazole or other azole antifungals, as determined by the Investigator. (Part A
Only)
- History of allergy, severe adverse reaction, intolerance, or hypersensitivity to
carbamazepine, carboxamide derivatives (eg, oxcarbazepine), or other drugs that are
structurally-related to carbamazepine, which include, but are not limited to tricyclic
antidepressants (eg, amitriptyline, desipramine, imipramine, protriptyline, or
nortriptyline), as judged by the Investigator. (Part B Only)
- Individuals who have Asian ancestry (including those who have one or more Asian
grandparents). (Part B Only)
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