| Eligibility |
Inclusion Criteria:
- Healthy male subjects between 18 and 60 years of age, with body mass index of 18.0 to
30.0 kg/m2. Body weight: =55 kg,and = 100 kg.
- In good health, determined by no clinically significant findings from medical history,
physical examination, 12-lead ECG, vital sign measurements, clinical laboratory
evaluations.
- Regular bowel movements (ie, average production of = 1 or = 3 bowel movements a day).
- Adhere to specific contraception requirements
- Creatinine clearance = 90 mL/min/1.73 m2.
- Aspartate aminotransferase and alanine aminotransferase must be =2.5 × upper limit of
normal (ULN) and total bilirubin =1.5 × ULN.
Exclusion Criteria:
- Significant history or clinical manifestation of any metabolic, allergic,
dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI,
neurological, respiratory, endocrine, or psychiatric disorder.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as
judged by the investigator, or history of hypersensitivity to DZD9008, its excipients,
or drugs with a similar chemical structure or class.
- History of stomach or intestinal surgery history or presence of hepatic or renal
disease or surgical procedure that would potentially alter absorption and/or excretion
of orally-administered drugs (uncomplicated appendectomy and hernia repair will be
allowed; cholecystectomy will not be allowed).
- Any clinically significant abnormalities in physical examination performed at
check-in, vital signs (supine systolic blood pressure >140 mmHg, diastolic blood
pressure >90 mmHg, and pulse rate =100 or =35 beats per minute) or clinical laboratory
evaluations as judged by the investigator (or designee).
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting
12-lead ECG, QTcF interval >450 msec, as judged by the investigator (or designee).
- A history of additional risk factors for Torsades de pointes (eg, heart failure,
hypokalemia, family history of Long QT syndrome).
- Positive/reactive results on screening tests for serum hepatitis B surface antigen,
hepatitis C antibody, or human immunodeficiency virus (Appendix 2).
- Acute illness, surgical procedures or trauma from within 2 weeks before screening
until the first administration of the IMP.
- Subjects with active malignancy or neoplastic disease in the previous 12 months.
- Ongoing or planned inpatient surgery, dental procedure, or hospitalization during the
study.
- Administration of a coronavirus disease 2019 (COVID-19) vaccine in the past 30 days
prior to dosing.
- Use or intend to use any medications/products known to alter drug AME processes,
including St. John's wort, within 30 days prior to check-in, unless deemed acceptable
by the investigator (or designee).
- Use or intend to use any prescription medications/products within 28 days prior to
check-in, unless deemed acceptable by the investigator (or designee). Exceptions may
be allowed on a case by case basis as agreed by the investigator and sponsor's medical
monitor if considered not to interfere with the aims of the study.
- Use or intend to use slow-release medications/products considered to still be active
within 14 days prior to check-in, unless deemed acceptable by the investigator (or
designee).
- Use or intend to use any nonprescription medications/products including vitamins,
minerals, and phytotherapeutic/herbal/plant-derived preparations, gastric pH
modifiers, and neutralizing antacids within 7 days prior to check-in, unless deemed
acceptable by the investigator (or designee).
- Subjects will avoid the use of any prescription or nonprescription
medications/products or herbal remedies that are strong/moderate CYP3A inhibitors or
inducers within 28 days prior to check-in through the end of study, unless deemed
acceptable by the Investigator.
- Subjects will avoid the use of any prescription or nonprescription
medications/products or herbal remedies that are transporter (eg, P-gp) inhibitors or
inducers within 28 days prior to the check-in through the end of study, unless deemed
acceptable by the Investigator.
- Subjects should avoid the use of proton pump inhibitors from 7 days prior to check-in
through 5 days postdose. For H2-antagonists or antacids, administration will follow
the staggered schedule per protocol.
- Subjects who received a live or live-attenuated vaccine in the 2 weeks prior to IMP
administration.
- Participation in a clinical study involving administration of an investigational drug
(new chemical entity defined as a compound which has not been approved for marketing)
or participation in any other clinical study (including methodology studies where no
drugs were given) in the past 90 days prior to dosing.
- Subjects who have participated in any radiolabeled drug studies in the last 12 months
prior to check-in.
- Have previously completed or withdrawn from this study or any other study
investigating DZD9008 and have previously received DZD9008.
- History of alcohol abuse or excessive alcohol consumption, defined as > 21 units per
week for males. One unit of alcohol equals 8.5 oz (250 mL) beer, 0.85 oz (25 mL)
liquor, or 2.4 oz (125 mL) wine.
- Positive urine drug detected at screening, positive urinary alcohol test result or
positive urine drug detected at check-in.
- History or suspected history of alcoholism or drug/chemical abuse within 2 years prior
to check-in, as judged by the investigator (or designee).
- Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or
positive cotinine at screening or check-in.
- Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages
within 7 days prior to check-in.
- Receipt of blood products within 2 months prior to check-in.
- Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to
screening, platelets from 6 weeks prior to screening, or any blood loss greater than
500 mL during the 3 months prior to screening.
- Poor peripheral venous access.
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