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

NCT ID: NCT04909242

Last Updated: 2022-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-21
• Study Completion Date: 2022-02-07

Brief Summary

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).

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

single oral dose of DZD9008

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

Group Type: EXPERIMENTAL

DZD9008

Intervention Type: 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.

single oral dose of placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

In the double blind, randomised, placebo-controlled trial (Part A - SAD), healthy adult participants will be randomized to receive matching placebo for DZD9008 at different dose levels. There are 5 planned dose cohorts of matching placebo for DZD9008, starting from 50 mg once daily.

single oral dose of DZD9008 (300 mg, tablet)

Group Type: EXPERIMENTAL

DZD9008

Intervention Type: DRUG

Healthy adult participants will be randomized to receive DZD9008 single dose at a defined dose under a cross-over condition with or without food (low-fat in Part B; high-fat in Part D).

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

Group Type: EXPERIMENTAL

DZD9008

Intervention Type: DRUG

In Part C, healthy adult participants will be enrolled to receive a single dose of DZD9008 as suspension in period 1 and as tablet in period 2.

Interventions

DZD9008

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.

Intervention Type: DRUG

Placebo

In the double blind, randomised, placebo-controlled trial (Part A - SAD), healthy adult participants will be randomized to receive matching placebo for DZD9008 at different dose levels. There are 5 planned dose cohorts of matching placebo for DZD9008, starting from 50 mg once daily.

Intervention Type: DRUG

DZD9008

In Part C, healthy adult participants will be enrolled to receive a single dose of DZD9008 as suspension in period 1 and as tablet in period 2.

Intervention Type: DRUG

DZD9008

Healthy adult participants will be randomized to receive DZD9008 single dose at a defined dose under a cross-over condition with or without food (low-fat in Part B; high-fat in Part D).

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dizal Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Dickerson

Role: PRINCIPAL_INVESTIGATOR

PRA Health Sciences

Locations

PRA Health Sciences

Lenexa, Kansas, United States

Countries

United States

Other Identifiers

DZ2021E0004

Identifier Type: -

Identifier Source: org_study_id