Clinical trial NCT04909242: Assessing the Safety, Tolerability and Pharmacokinetics(PK) of DZD9008 and the Effect of Low-fat Meal on PK of DZD9008 in Healthy Adult Participants
Official title: A Phase 1 Randomised, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of DZD9008 Following Single Ascending Dose and the Effect of Low-fat Meal on Pharmacokinetics of DZD9008 in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Dizal Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-06-01
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: up to 14 days after study drug administration
measure: Number of participants with clinically significant laboratory assessment abnormalities
timeFrame: up to 14 days after study drug administration
measure: Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
timeFrame: up to 14 days after study drug administration
measure: Number of participants with clinically significant abnormalities in LVEF
timeFrame: up to 14 days after study drug administration
measure: Number of participants with clinically significant abnormalities in FEV1%
timeFrame: up to 14 days after study drug administration
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of DZD9008
timeFrame: up to 10 days after study drug administration
measure: Time to reach maximum plasma concentration (tmax)
timeFrame: up to 10 days after study drug administration
measure: Area under the concentration-time curve from time 0 (pre-dose) to the time of the dosing interval (AUC0-t)
timeFrame: up to 10 days after study drug administration
measure: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
timeFrame: up to 10 days after study drug administration
measure: Apparent total plasma clearance (CL/F)
timeFrame: up to 10 days after study drug administration
measure: Apparent volume of distribution (Vz/F)
timeFrame: up to 10 days after study drug administration
measure: Mean residence time (MRT)
timeFrame: up to 10 days after study drug administration
measure: Terminal elimination half-life (t1/2)
timeFrame: up to 10 days after study drug administration
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: PRA Health Sciences
state: Kansas
Study officials:
affiliation: PRA Health Sciences
name: Daniel Dickerson
role: PRINCIPAL_INVESTIGATOR
References: