Assessing the Safety, Tolerability and Pharmacokinetics(PK) of DZD9008 and the Effect of Low-fat Meal on PK of DZD9008 in Healthy Adult Participants

Dizal Pharma

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo; Drug: DZD9008

Study type: Interventional

Funder types: Industry

Identifiers

NCT04909242

DZ2021E0004

Details and patient eligibility

About

This is a Phase 1, randomised, double-blind, placebo-controlled, single ascending dose sequential group study in healthy participants. This study consists of three parts: Part A (single dose escalation, SAD) , Part B (food effect, FE) and Part C (relative bioavailability, BA).

Enrollment: 78 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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78 participants in 4 patient groups, including a placebo group

single oral dose of DZD9008

Experimental group

Description:

single dose of DZD9008 (50 mg, 100 mg, 200 mg, 300 mg and 400 mg, tablet)

Treatment:

Drug: DZD9008

Drug: DZD9008

Drug: DZD9008

single oral dose of placebo

Placebo Comparator group

Description:

single dose of placebo (matching placebo, 50 mg, 100 mg, 200 mg, 300 mg and 400 mg, tablet)

Treatment:

Drug: Placebo

single oral dose of DZD9008 (300 mg, tablet)

Experimental group

Treatment:

Drug: DZD9008

Drug: DZD9008

Drug: DZD9008

single oral dose of DZD9008 (100 mg, tablet or suspension)

Experimental group

Treatment:

Drug: DZD9008

Drug: DZD9008

Drug: DZD9008