Assessing the Safety, Tolerability and Pharmacokinetics(P... | NCT04909242

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
single oral dose of DZD9008	Experimental	single dose of DZD9008 (50 mg, 100 mg, 200 mg, 300 mg and 400 mg, tablet)	Drug: DZD9008
single oral dose of placebo	Placebo Comparator	single dose of placebo (matching placebo, 50 mg, 100 mg, 200 mg, 300 mg and 400 mg, tablet)	Drug: Placebo
single oral dose of DZD9008 (300 mg, tablet)	Experimental		Drug: DZD9008
single oral dose of DZD9008 (100 mg, tablet or suspension)	Experimental		Drug: DZD9008

Interventions

Name	Type	Description	Arm Group Labels	Other Names
DZD9008	Drug	In the double blind, randomised, placebo-controlled trial (Part A - SAD), healthy adult participants will be randomized to receive DZD9008 at different dose levels. There are 5 planned dose cohorts, starting from 50 mg once daily. If tolerated, subsequent cohorts will test increasing doses of DZD9008 or matching placebo, namely 100 mg, 200 mg, 300 mg and 400 mg.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs)	To assess the safety and tolerability of DZD9008 following oral administration of single ascending doses in healthy adult participants.	up to 14 days after study drug administration
Number of participants with clinically significant laboratory assessment abnormalities	To assess the safety and tolerability of DZD9008 following oral administration of single ascending doses in healthy adult participants.	up to 14 days after study drug administration
Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities	To assess the safety and tolerability of DZD9008 following oral administration of single ascending doses in healthy adult participants.	up to 14 days after study drug administration
Number of participants with clinically significant abnormalities in LVEF	To assess the safety and tolerability of DZD9008 following oral administration of single ascending doses in healthy adult participants.	up to 14 days after study drug administration
Number of participants with clinically significant abnormalities in FEV1%	To assess the safety and tolerability of DZD9008 following oral administration of single ascending doses in healthy adult participants.	up to 14 days after study drug administration

Secondary Outcomes

Measure	Description	Time Frame
Maximum plasma concentration (Cmax) of DZD9008		up to 10 days after study drug administration
Time to reach maximum plasma concentration (tmax)		up to 10 days after study drug administration

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants must be able to understand the nature of the trial and provide a signed and dated, written informed consent form before any study-specific procedures, sampling and analyses.
Provision of signed and dated written Optional Genetic Research informed consent prior to collection of samples for optional genetic research.
Healthy male or female participants aged 18 to 60 years (inclusive), with BMI 18.0 to 30.0 kg/m2 (inclusive). Body weight: ≥ 55 kg for male, ≥ 45 kg for female.
Healthy participants defined as the absence of acute or chronic clinically significant deviations from normal in medical history, physical examination, visual assessment, electrocardiogram (ECG), and clinical laboratory determinations at screening.
Participants must agree to practice effective contraception.
Normal baseline PFTs (≥ 80% predicted normal for spirometry, lung volumes).
Normal baseline ECG (QTcF < 450 msec, PR < 210 msec).
Non-smoker (not smoked within 3 months).
Liver biochemistry parameters: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN
Adequate organ function including hepatic, renal, cardiac, visual and bone marrow function as determined by the investigator.

Exclusion Criteria:

Ongoing or prior pulmonary disease including asthma, chronic obstructive pulmonary disease, interstitial lung disease and pneumonitis including but not limited to drug-related pneumonitis.
Women who are breast feeding.
Positive pregnancy test prior to study entry.
History of malignancy of any type, with the exception of the following: surgically excised non-melanomatous skin cancers more than 5 years prior to receiving IP.
A history of additional risk factors for TdP (e.g. heart failure, hypokalemia, family history of Long QT syndrome).
No prior history of atrial fibrillation within 6 months prior to first dosing of DZD9008
Manifestations of malabsorption due to prior GI surgery, GI disease, or for an unknown other reason that may affect the absorption of DZD9008-. Pulmonary infections or other active infection within 30 days of informed consent
History of bleeding disorder (including hemophilia, Von Willebrand disease, etc), history of stroke or intracranial haemorrhage within 6 months before study drug administration.
Judgement by the investigator that the participant is not likely to comply with study procedures, restrictions and requirements.
Positive serology or a known history of hepatitis B virus (HBV), hepatitis C virus (HCV), HIV.
Resting blood pressure > 140/90 mmHg at screening .
Resting pulse rate < 45 beats per minute.
History of severe allergy or hypersensitivity reaction or ongoing allergy or hypersensitivity reaction, as judged by investigator, or history of hypersensitivity to EGFR/HER2/BTK inhibitors.