Drug-drug Interactions Between DZD9008 and Itraconazole/Carbamazepine

NCT05418582 | Completed Phase 1 FDA Drug

• 1 other identifier: DZ2021E0008
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, single-center, nonrandomized, open-label, 2-part, fixed-sequence, drug-drug interaction (DDI) study to assess the effect of multiple doses of itraconazole, a CYP3A4 enzyme inhibitor, on the single dose PK of DZD9008 in healthy adult subjects (Part A) and to assess the effect of multiple doses of carbamazepine, a CYP3A4 inducer, on the single dose PK of DZD9008 in healthy adult subjects (Part B).

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (8)

• Maximum plasma concentration (Cmax) of DZD9008 when dosed alone or coadministered with itraconazole (Part A）

  up to 11 days after study drug administration

• Time to reach maximum plasma concentration (tmax) of DZD9008 when dosed alone or coadministered with itraconazole (Part A)

  up to 11 days after study drug administration

• Area under the concentration-time curve from time 0 to time of last quantifiable concentration (AUC0-t) when dosed alone or coadministered with itraconazole (Part A)

  up to 11 days after study drug administration

• Area under the concentration-time curve from time 0 to infinity (AUC0-inf) when dosed alone or coadministered with itraconazole (Part A)

  up to 11 days after study drug administration

• Maximum plasma concentration (Cmax) of DZD9008 when dosed alone or coadministered with carbamazepine (Part B)

  up to 10 days after study drug administration

• Time to reach maximum plasma concentration (tmax) of DZD9008 when dosed alone or coadministered with carbamazepine (Part B)

  up to 10 days after study drug administration

• Area under the concentration-time curve from time 0 to time of last quantifiable concentration (AUC0-t) when dosed alone or coadministered with carbamazepine (Part B)

  up to 10 days after study drug administration

• Area under the concentration-time curve from time 0 to infinity (AUC0-inf) when dosed alone or coadministered with carbamazepine (Part B)

  up to 10 days after study drug administration

Study Arms (2)

DZD9008 and itraconazole

EXPERIMENTAL

Subjects in arm 1 will receive DZD9008 single dose on Day 1, and the second dose of DZD9008 along with itraconazole after the wash-out period.

Drug: DZD9008 and intraconazole

DZD9008 and carbamazepine

EXPERIMENTAL

Subjects in arm 2 will receive DZD9008 single dose on Day 1, and the second dose of DZD9008 along with carbamazepine after the wash-out period.

Drug: DZD9008 and carbamazepine

Interventions

DZD9008 and intraconazole DRUG

All subjects will receive DZD9008 single dose on Day 1, and the second dose of DZD9008 along with itraconazole after the wash-out period.

DZD9008 and itraconazole

DZD9008 and carbamazepine DRUG

All subjects will receive DZD9008 single dose on Day 1, and the second dose of DZD9008 along with carbamazepine after the wash-out period.

DZD9008 and carbamazepine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects aging 18 to 55 years with Body mass index (BMI) 18.0 to 30.0 kg/m2.
• Weight : ≥ 55 kg for males and ≥ 45 kg for females.
• Healthy status as defined by the absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic disease following a detailed medical and surgical history, a complete physical examination.
• Ability and willingness to abstain from alcohol-, caffeine-, and methylxanthine-containing beverages or food during the stay in study center.
• No clinically significant hematological or coagulation abnormalities, as judged by the Investigator.
• Male subjects and female subjects of childbearing potential must agree to use protocol-specified method(s) of contraception and comply with pregnancy precautions.
• All nonregular medication (including over-the-counter \[OTC\] medication, health supplements, and herbal remedies such as St. John's wort extract) must have been stopped at least 14 days or 5 half-lives, if known (whichever is longer) prior to the admission to the clinical research center.
• Normal baseline pulmonary function tests (≥ 80% predicted normal for spirometry, lung volumes).
• Normal baseline ECG (QTcF \< 450 msec, PR \< 220 msec).
• Adequate organ function including hepatic, renal, cardiac, and bone marrow function, as determined by the Investigator.

You may not qualify if:

• Employee of PRA or the Sponsor.
• Any condition which, in the opinion of the Investigator, would interfere with the subject's ability to provide informed consent, comply with study instructions, confound interpretation of study results, or endanger the subject if he or she takes part in the trial.
• Women who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 30 days after dosing of study drug.
• For all females of childbearing potential: positive pregnancy test at screening and at admission to the clinic.
• Males with female partners who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after dosing of study drug.
• Use of any investigational drug or device within 30 days of the first dose of study drug.
• Any disease which, in the opinion of the Investigator, poses an unacceptable risk to the subjects.
• Clinically relevant issues of visual function as determined from the medical history and physical exams, as judged by the Investigator.
• Clinically significant history of any drug sensitivity, drug allergy, or food allergy, as determined by the Investigator (such as anaphylaxis, hepatotoxicity, or treatment with steroids or epinephrine). Confirmatory circumstances would include treatment with epinephrine or in Emergency Department.
• History of allergy or hypersensitivity to DZD9008, or other drugs similar in class (EGFR/HER2/BTK inhibitor) or similar in chemical structure to DZD9008, as judged by the Investigator.
• History of major surgery or blood transfusion within 30 days prior to the first drug administration.
• History of malignancy of any type, except for the following: surgically excised non-melanomatous skin cancers more than 5 years prior to receiving the investigational medicinal product.
• Evidence of clinically significant or relevant renal, hematological, endocrine, pulmonary, GI, cardiovascular, hepatic, psychiatric, neurological, or allergic disease, as judged by the Investigator.
• Manifestation of malabsorption due to prior GI surgery, GI disease, or any other reason that may affect the absorption of DZD9008.
• Positive result from a COVID-19 test per local policy and requirement.

Sponsors & Collaborators

• Dizal Pharmaceuticals: lead

Study Sites (1)

Pharmaceutical Research Associates, Inc.

Lenexa, Kansas, 66219, United States

Location

MeSH Terms

Interventions

Carbamazepine

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tianwei Zhang

  Dizal Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2022
• First Posted: June 14, 2022
• Study Start: January 25, 2022
• Primary Completion: June 1, 2022
• Study Completion: December 8, 2022
• Last Updated: June 23, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)