Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001413112
Ethics application status
Approved
Date submitted
3/09/2019
Date registered
15/10/2019
Date last updated
21/10/2021
Date data sharing statement initially provided
15/10/2019
Date results information initially provided
21/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A DDI Study to Evaluate the Effects of Itraconazole and Fluoxetine on AK0529 in Healthy Volunteers
Scientific title
A Two Part, Open-Label, Fixed Sequence Study to Evaluate the Effects of Multiple Doses of Itraconazole and Fluoxetine on the Pharmacokinetics of a Single Dose of AK0529 in Healthy Volunteers
Secondary ID [1] 299172 0
AK0529-1004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Syncytial Virus Infection 314265 0
Condition category
Condition code
Infection 312620 312620 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects fulfilling the eligibility criteria will be enrolled sequentially into one of two cohorts, to receive either AK0529 and itraconazole or AK0529 and fluoxetine. A total of 28 healthy volunteers will be enrolled, 14 in each cohort. The two cohorts are parallel cohorts investigating the effect of multiple doses of itraconazole and fluoxetine on the PK parameters of a single dose of AK0529, respectively.

Subjects in Cohort 1 will receive a single oral dose of AK0529 on Day 1 and, after a wash-out period of 4 days a single oral dose of itraconazole once daily on Days 5-12, with co-administration of AK0529 on Day 8. Subjects will be admitted to the clinical research unit (CRU) on Day -1 before AK0529 dosing and remain in the CRU for a period of 21 days, during which the study personnel will dispense drugs on each administration day and monitor the subject's adhernece to study interventions, until all safety assessments have been completed on Day 20.

Subjects in Cohort 2 will receive a single oral dose of AK0529 on Day 1 and, after a wash-out period of 4 days a single oral dose of fluoxetine once daily on Days 5-17, with co-administration of AK0529 on Day 14. Subjects will be admitted to the CRU on Day -1 before AK0529 dosing and remain in the CRU for a period of 26 days, during which the study personnel will dispense drugs on each administration day and monitor the subject's adhernece to study interventions, until all safety assessments have been completed on Day 25.

The detailed treatment drugs information is as below:

1. AK0529 (Ziresovir)
100mg/capsule, oral administration

2. Itraconazole
Oral solution, 10mg/ml, 20ml (200mg)

3. Fluoxetine
Oral capsule, 20mg/capsule
Intervention code [1] 315466 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321269 0
Estimation of pharmacokinetic (PK) parameters for AK0529 with and without the coadministration of itraconazole or fluoxetine, which will be assessed via blood (plasma) samples.

• Time to maximum measured plasma concentration (tmax)
• Maximum measured plasma concentration (Cmax)
• Area under the plasma concentration versus time curve to 24 hours (AUC0-24)
• Area under the plasma concentration versus time curve to the last measurable concentration (AUC0-t)
Timepoint [1] 321269 0
AK0529:
Pre 1st dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post 1st dose.
Pre 2nd dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post 2nd dose.

Itraconazole:
Pre-dose on days Days 6, 7 and 8 in cohort 1

Fluoxetine:
Pre-dose on days 12, 13 and 14 in cohort 2
Secondary outcome [1] 374509 0
Incidence, nature, and severity of treatment emergent adverse events (TEAEs).
Timepoint [1] 374509 0
Since the ICF is signed by the subject, till his/her completion of the study.
Secondary outcome [2] 375073 0
Incidence rates of adverse events (AEs) prior to, during, and after administration of treatments. Adverse events can be spontaneously reported by the subject, observed by the Investigator (either directly or by laboratory or other assessments) or elicited by general questioning. For example, headache and dizziness can be assessed via subject’s self-report, while blood creatinine phosphokinase increased can be assessed via laboratory results.
Timepoint [2] 375073 0
Since the ICF is signed by the subject, till his/her completion of the study.
Secondary outcome [3] 375077 0
Proportion of subjects who discontinue the study due to AEs. This outcome is assessed via counting the number of subjects who discontinue the trial before completing all drug administrations or assessments, due to adverse event. The reason of each discontinuing will be determined by study-specific questionnaire.
Timepoint [3] 375077 0
Since the ICF is signed by the subject, till his/her completion of the study.
Secondary outcome [4] 375855 0
Proportion of subjects completing the study. This outcome is assessed via counting the number of subjects who complete all drug administrations and assessments for this study.
Timepoint [4] 375855 0
Since the ICF is signed by the subject, till his/her completion of the study.

Eligibility
Key inclusion criteria
1. Completion of the written informed consent process.
2. Male or female subjects aged 18 to 55 years of age, with a body mass index (BMI) within the range of 18 to 30 kg/m2 (inclusive).
3. Subjects not pregant, or will not be pregant, and agreed to use effective contraception method(s) during the study per protocol requirement.
4. Good health based on no clinically significant findings in the medical history, physical examination, or clinical laboratory test results.
5. Willing and able to comply with all study activities and procedures.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has a QTcF interval > 450 msec.
2. Has a history or presence of prolonged QTc or family history of long QT syndrome.
3. Has any finding that, in the opinion of the investigator, would compromise the subject’s ability to fulfill the protocol visit schedule or study requirements.
4. Has current evidence, or history of any clinically significant medical or psychiatric condition or observed abnormality that could potentially compromise subject safety or evaluation of PK parameters.
5. If female, is currently pregnant or breastfeeding.
6. Has a history of, or current infection with, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, or has a history of liver disease, including unexplained fluctuations in liver function tests.
7. Has used CYP3A4 or CYP2D6 inhibitors or inducers or P-gp inhibitors within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or anticipates a need to use any CYP3A4 or CYP2D6 inhibitors or inducers, or P-gp inhibitors during the study period.
8. Use of prescription or non-prescription drugs, herbal products, nutritional supplements or ‘alternative’ medication or remedies within 14 days or 5 half-lives (whichever is the longer) prior to the first dose of study drug.
9. Intake of grapefruit, grapefruit juice or grapefruit-related citrus fruits within 7 days prior to the first dose of the study medication.
10. Has a known intolerance or allergy to AK0529, itraconazole, fluoxetine or related compounds.
11. Previous intolerance to SSRI or SNRI drugs.
12. Has a history or current presence of psychiatric symptoms including anxiety, mood disturbance, suicidal ideation or self-harming behaviour.
13. Has a history of seizure, except for simple, febrile convulsion as a child.
14. History of regular alcohol consumption exceeding a weekly intake of more than 21 units for males and more than 14 units for females within 6 months of screening.
15. Is a smoker, or has ceased using tobacco-containing or nicotine-containing products within 3 months of screening, not including light or social smoking not exceeding the equivalent of 5 cigarettes per week, and/or has a positive cotinine test at screening or Day -1.
16. Excessive consumption of beverages containing xanthine bases.
17. Has used alcohol-, caffeine- or xanthine-containing products within 72 hours prior to admission on Day -1.
18. Has a positive urine toxicological screen for cotinine (or saliva test), benzodiazepines, opioids amphetamine/methamphetamine, cannabinoids or cocaine at screening or Day -1.
19. Has a positive alcohol breath test at screening or Day -1.
20. Has donated blood of more than 500 ml within 4 weeks prior to screening.
21. Participation in any investigational product study within 12 weeks or five half-lives (whichever is longer) prior to the first dose of the study medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/10/2019
Actual
15/10/2019
Date of last participant enrolment
Anticipated
Actual
12/11/2019
Date of last data collection
Anticipated
Actual
3/11/2020
Sample size
Target
28
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 303715 0
Commercial sector/Industry
Name [1] 303715 0
Ark Biosciences Pty Ltd
Country [1] 303715 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Ark Biosciences Pty Ltd
Address
Suite 1204, 219-227 Elizabeth Street, Sydney NSW 2000, Australia
Country
Australia
Secondary sponsor category [1] 303828 0
None
Name [1] 303828 0
NA
Address [1] 303828 0
NA
Country [1] 303828 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304240 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 304240 0
55 Commercial Road, Melbourne, VIC, 3004
Ethics committee country [1] 304240 0
Australia
Date submitted for ethics approval [1] 304240 0
26/08/2019
Approval date [1] 304240 0
30/09/2019
Ethics approval number [1] 304240 0

Summary
Brief summary
This Phase I study will evaluate the drug-drug interaction of the investigational medicinal and substrate product AK0529, when administered with either itraconazole, a strong cytochrome P450 3A4 and P-glycoprotein inhibitor (Cohort 1) or fluoxetine, a strong cytochrome P450 2D6 (Cohort 2) inhibitor in healthy adult subjects. The primary objective of this study is to evaluate the effect of multiple doses of itraconazole and fluoxetine on the pharmacokinetics of a single dose of AK0529. This is a two part, open-label, fixed sequence study to be conducted at a single clinical research centre.
Trial website
Trial related presentations / publications
Public notes
The two cohorts in this study are not comparable, but to independently investigate the AK0529 PK parameters under the effection of itraconazole or fluoxetine administration.

Contacts
Principal investigator
Name 96246 0
Dr Ben Snyder
Address 96246 0
Nucleus Network Pty Ltd
Level 5, Burnet Tower, 89 Commercial Road, Melbourne, VIC 3004, Australia
Country 96246 0
Australia
Phone 96246 0
+61 3 8535 4806
Fax 96246 0
Email 96246 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 96247 0
Mr Jimmy Gu
Address 96247 0
Ark Biosciences Inc. 780 Cailun Road, Suite 701, Pudong, Shanghai 201203
Country 96247 0
China
Phone 96247 0
+862158350139
Fax 96247 0
Email 96247 0
info@arkbiosciences.com
Contact person for scientific queries
Name 96248 0
Mr Jimmy Gu
Address 96248 0
Ark Biosciences Inc. 780 Cailun Road, Suite 701, Pudong, Shanghai 201203
Country 96248 0
China
Phone 96248 0
+862158350139
Fax 96248 0
Email 96248 0
info@arkbiosciences.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.