Drug-drug Interactions Between AZD4205 and Itraconazole/Carbamazepine

NCT05486949 | Completed Phase 1 FDA Drug

• 1 other identifier: DZ2021J0002
• Study Type: interventional
• Target: 32
• 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 AZD4205 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 AZD4205 in healthy adult subjects (Part B).

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (8)

• Maximum plasma concentration (Cmax) of AZD4205 when dosed alone or coadministered with itraconazole (Part A)

  up to 10 days after study drug administration when AZD4205 dosed alone; up to 18 days after study drug administration when coadministered with itraconazole

• Time to reach maximum plasma concentration (tmax) of AZD4205 when dosed alone or coadministered with itraconazole (Part A)

  up to 10 days after study drug administration when AZD4205 dosed alone; up to 18 days after study drug administration when coadministered with itraconazole

• 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 10 days after study drug administration when AZD4205 dosed alone; up to 18 days after study drug administration when coadministered with itraconazole

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

  up to 10 days after study drug administration when AZD4205 dosed alone; up to 18 days after study drug administration when coadministered with itraconazole

• Maximum plasma concentration (Cmax) of AZD4205 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 AZD4205 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)

AZD4205 and carbamazepine

EXPERIMENTAL

Subjects in arm 1 will receive AZD4205 single dose on Day 1, and the second dose of AZD4205 along with carbamazepine after the wash-out period.

Drug: AZD4205 and carbamazepine

AZD4205 and itraconazole

EXPERIMENTAL

Subjects in arm 2 will receive AZD4205 single dose on Day 1, and the second dose of AZD4205 along with itraconazole after the wash-out period.

Drug: AZD4205 and itraconazole

Interventions

AZD4205 and carbamazepine DRUG

All subjects will receive AZD4205 single dose on Day 1, and the second dose of AZD4205 along with carbamazepine after the wash-out period.

AZD4205 and carbamazepine

AZD4205 and itraconazole DRUG

All subjects will receive AZD4205 single dose on Day 1, and the second dose of AZD4205 along with itraconazole after the wash-out period.

AZD4205 and itraconazole

Eligibility Criteria

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

You may qualify if:

• Willing to participate in the study, give written informed consent, and comply with the study restrictions.
• Sex: male or female; females may be of childbearing potential, of nonchildbearing potential, or postmenopausal.
• Age: 18 to 55 years, inclusive, at screening.
• Body mass index (BMI): 18.0 to 30.0 kg/m2, inclusive, at screening.
• Weight: ≥55 kg for males and ≥45 kg for females at screening.
• Status: healthy subjects.
• Healthy status as defined by the absence of evidence of any clinically significant, in the opinion of the investigator, active, or chronic disease.
• Ability and willingness to abstain from alcohol-, caffeine-, and methylxanthine containing beverages or food from 72 hours (3 days) prior to admission until discharge from the clinical facility.
• 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 methods of contraception and comply with pregnancy precautions as described in the protocol.
• All prescription medications must have been stopped at least 28 days or 5 half lives, if known prior to the admission to the clinical research center.
• All over the counter medication must have been stopped at least 14 days or 5 half-lives, prior to the admission to the clinical research center.
• Normal baseline ECG (QTcF \<450 msec, PR \<220 msec).
• Adequate organ function, defined by the absence of any clinically significant abnormalities, as judged by the investigator, of the relevant baseline clinical safety assessments.

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 the last dose of study drug.
• For all females of childbearing potential: positive pregnancy test at screening or 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 the last dose of study drug.
• Use of any investigational drug or device within 30 days, or investigational biologics within 120 days before the first dose of study drug.
• Any disease which, in the opinion of the investigator, poses an unacceptable risk to the subject.
• 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.
• History of allergy or hypersensitivity to AZD4205, or other drugs similar in class or similar in chemical structure to AZD4205, 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.
• Evidence of clinically significant or relevant renal, hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
• Manifestation of malabsorption due to prior gastrointestinal surgery, gastrointestinal disease, or any other reason that may affect the absorption of AZD4205.
• Positive result from a COVID-19 test per site 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; Itraconazole

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines

Study Officials

• Shirlian Xu

  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: August 2, 2022
• First Posted: August 4, 2022
• Study Start: July 27, 2022
• Primary Completion: October 8, 2022
• Study Completion: October 11, 2022
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)