Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000437167
Ethics application status
Approved
Date submitted
12/03/2019
Date registered
18/03/2019
Date last updated
11/07/2019
Date data sharing statement initially provided
18/03/2019
Date results information initially provided
11/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to investigate the effect of AB-506 on Single Dose Pharmacokinetics of an Oral Contraceptive in Healthy Female Subjects
Scientific title
A Study to Evaluate the Effect of AB-506 on the Single Dose Pharmacokinetics of an Oral Contraceptive in Healthy Female Subjects
Secondary ID [1] 297584 0
AB-506-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Infection (CHB) 311840 0
Condition category
Condition code
Infection 310440 310440 0 0
Other infectious diseases
Reproductive Health and Childbirth 310472 310472 0 0
Contraception

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will consist of 2 treatment periods. A popular choice among women of child-bearing potential is a monophasic oral contraceptive combination containing a fixed dose of 3 mg drospirenone (DRSP) and 0.02 mg ethinyl estradiol (EE). The study will be conducted in approximately 32 subjects. In Period 1, healthy female subjects will receive a single dose of DRSP/EE on Day 1, administered as oral tablet, followed by a washout of 5 days. In Period 2, subjects will receive AB-506 400 mg, administered as oral tablet, once daily for 13 days, with a single oral dose of DRSP/EE (same dose as Day 1) co-administered on Day 15. The duration of the study will be approximately 7 weeks, including the screening period. Subjects will take their study drug in the presence of study staff. Compliance will be confirmed by a mouth check after dosing.
Intervention code [1] 313850 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319336 0
To assess the effect of 400 mg once daily dosing of AB-506 on the single Dose pharmacokinetics (PK) of drospirenone (DRSP). PK parameters (Cmax, AUC) of DRSP and EE will be assessed following administration of DRSP.
Timepoint [1] 319336 0
In Period 1: Plasma sample for PK is collected on Day 1, Day 2 (24hrs), Day 3 (48 hrs), Day 4 (72 hrs) and Day 5 (96 hrs).
In Period 2: Plasma sample for PK is collected on Day 10, Day 13, Day 14, Day 15 , Day 16, Day 17, Day 18 and Day 19.
Primary outcome [2] 319456 0
To assess the effect of 400 mg once daily dosing of AB-506 on the single Dose pharmacokinetics (PK) of ethinyl estradiol (EE). PK parameters (Cmax, AUC) of EE will be assessed following administration of EE..
Timepoint [2] 319456 0
In Period 1: Plasma sample for PK is collected on Day 1, Day 2 (24hrs), Day 3 (48 hrs), Day 4 (72 hrs) and Day 5 (96 hrs).
In Period 2: Plasma sample for PK is collected on Day 10, Day 13, Day 14, Day 15 , Day 16, Day 17, Day 18 and Day 19.
Secondary outcome [1] 367825 0
To characterize the steady state PK of AB-506 following once daily administration of 400 mg. PK parameters (Cmax, Tmax, area under the concentration-time curve from time 0 to end of dosing interval (AUCtau), plasma concentration at end of the dosing interval (Ctau)) will be assessed following administration of AB-506.
Timepoint [1] 367825 0
In Period 2: Plasma sample for PK is collected on Day 10, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18 and Day 19.
Secondary outcome [2] 367826 0
To characterize the single dose PK of DRSP in the absence of AB-506. Following PK parameters are assessed:
• Single dose DRSP Cmax, Tmax, AUC(0-t), AUCinf, half-life (t1/2)
Timepoint [2] 367826 0
In Period 1 (Absence of AB-506): Plasma sample for PK is collected on Day 1, Day 2 (24hrs), Day 3 (48 hrs), Day 4 (72 hrs) and Day 5 (96 hrs).
Secondary outcome [3] 367827 0
To assess the safety of AB-506 in combination with an oral contraceptive in healthy female subjects
Timepoint [3] 367827 0
Frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs) which is monitored throughout the study starting from screening till early termination and laboratory abnormalities includes chemistry, coagulation, hematology and urine parameters. Laboratory tests will be completed after an overnight fast of at least 8 hours on screening, day -1 and day 5 in period 1 and in period 2, laboratory tests will be performed on day 8, day 11 day 15, day 19 and day 22.
Secondary outcome [4] 367828 0
To assess the tolerability of AB-506 in combination with an oral contraceptive in healthy female subjects
Timepoint [4] 367828 0
Frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs) which is monitored throughout the study starting from screening till early termination and laboratory abnormalities includes chemistry, coagulation, hematology and urine parameters. Laboratory tests will be completed after an overnight fast of at least 8 hours on screening, day -1 and day 5 in period 1 and in period 2, laboratory tests will be performed on day 8, day 11 day 15, day 19 and day 22.
Secondary outcome [5] 368259 0
To characterize the single dose PK of DRSP in the presence of AB-506. Following PK parameters are assessed:
• Single dose DRSP Cmax, Tmax, AUC(0-t), AUCinf, half-life (t1/2)
Timepoint [5] 368259 0
In Period 2 (Presence of AB-506) : Plasma sample for PK is collected on Day 10, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18 and Day 19.
Secondary outcome [6] 368261 0
To characterize the single dose PK of EE in the presence of AB-506. Following PK parameters are assessed:
Single dose EE Cmax, Tmax, AUC(0-t), AUCinf, t1/2.
Timepoint [6] 368261 0
In Period 2 (Presence of AB-506) : Plasma sample for PK is collected on Day 10, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18 and Day 19.
Secondary outcome [7] 368262 0
To characterize the single dose PK of EE in the absence of AB-506. Following PK parameters are assessed:
Single dose EE Cmax, Tmax, AUC(0-t), AUCinf, t1/2.
Timepoint [7] 368262 0
In Period 1 (Absence of AB-506): Plasma sample for PK is collected on Day 1, Day 2 (24hrs), Day 3 (48 hrs), Day 4 (72 hrs) and Day 5 (96 hrs).

Eligibility
Key inclusion criteria
1. Healthy females aged 18–50, inclusive. Healthy subjects are defined as individuals free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results.
2. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
i. Not a WOCBP
OR
ii. A WOCBP who agrees to using a non-hormonal contraceptive at least 4 weeks prior to the first dose of the study, during the study, and 30 days after the last dose is administered. Subject should be willing to use acceptable forms of non-hormonal contraceptives.
3. Body mass index (BMI) >/=18 kg/m2 and < /=30 kg/m2.
4. Capable of giving signed informed consent; able to understand and comply with protocol requirements, instructions, and protocol-related restrictions; and likely to complete the study as planned.
Minimum age
18 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Medical Status or History
1. Any known pre-existing medical or psychiatric condition that could interfere with the subject’s ability to provide informed consent or participate in study conduct, or that may confound study findings including, but not limited to a history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, or cardiovascular disease.
2. Positive pregnancy test at Screening or Day -1.
3. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
4. Participation in an investigational drug, vaccine, or medical device study within 30 days before study drug administration, or 90 days for a biologic study.
5. Any known or suspected hypersensitivity or previous severe reactions to any of the constituents of AB-506 or oral contraceptives, or history of any other allergy that, in the opinion of the Investigator, contraindicates participation in the trial.
6. Clinically significant ECG abnormalities prior to dosing (screening or day -1) that are confirmed by a repeat reading.
7. Clinically significant abnormalities in laboratory test results at screening or day -1 that are confirmed by a repeat reading.
8. Abnormal blood pressure at Screening, Day -1, or Day 1 pre-dose that is confirmed by a repeat reading and assessed as clinically significant by the Investigator.

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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
13/05/2019
Actual
16/05/2019
Date of last participant enrolment
Anticipated
Actual
17/06/2019
Date of last data collection
Anticipated
Actual
8/07/2019
Sample size
Target
32
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14204 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 27188 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 302134 0
Commercial sector/Industry
Name [1] 302134 0
Arbutus Biopharma Corporation
Country [1] 302134 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Arbutus Biopharma Corporation
Address
100 – 8900 Glenlyon Parkway
Burnaby, British Columbia
Canada V5J 5J8
Country
Canada
Secondary sponsor category [1] 301969 0
None
Name [1] 301969 0
Address [1] 301969 0
Country [1] 301969 0
Other collaborator category [1] 280583 0
Commercial sector/Industry
Name [1] 280583 0
Novotech (Australia) Pty Limited
Address [1] 280583 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280583 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302815 0
Bellberry Limited Human Research Ethics Committee
Ethics committee address [1] 302815 0
123 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 302815 0
Australia
Date submitted for ethics approval [1] 302815 0
13/03/2019
Approval date [1] 302815 0
07/05/2019
Ethics approval number [1] 302815 0

Summary
Brief summary
The study will evaluate the effect of the study drug, AB-506, on the single dose pharmacokinetics of an oral contraceptive in healthy female participants. The duration of the study will be approximately 7 weeks, including the screening period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91486 0
Dr Dr Oscar Walsh
Address 91486 0
Nucleus Network
Level 5, Burnet Tower, AMREP Precinct,
89 Commercial Road Melbourne, VIC 3004
Country 91486 0
Australia
Phone 91486 0
+61 3 8593 9800
Fax 91486 0
Email 91486 0
[email protected]
Contact person for public queries
Name 91487 0
Mr Arbutus Clinical Development
Address 91487 0
Arbutus Biopharma Corporation
701 Veterans Circle
Warminster, Pennsylvania
United States 18974
Country 91487 0
United States of America
Phone 91487 0
+1 267 469 0914
Fax 91487 0
Email 91487 0
[email protected]
Contact person for scientific queries
Name 91488 0
Mr Arbutus Clinical Development
Address 91488 0
Arbutus Biopharma Corporation
701 Veterans Circle
Warminster, Pennsylvania
United States 18974
Country 91488 0
United States of America
Phone 91488 0
+1 267 469 0914
Fax 91488 0
Email 91488 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to confidentiality and privacy reasons


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.