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Trial registered on ANZCTR


Registration number
ACTRN12624001286538
Ethics application status
Approved
Date submitted
4/10/2024
Date registered
22/10/2024
Date last updated
22/10/2024
Date data sharing statement initially provided
22/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
The womens Wellness Intrauterine Neuroimmune modulation Study Expansion Group: The effect of a new intrauterine device on pelvic pain in women.
Scientific title
A Phase 1B, single-centre, Expansion Group, randomised, double-blind, parallel-group study to investigate the tolerability and pharmacokinetics of the new Alyra Device (IUD) compared with the commonly used Mirena 'Trademark' Device.
Secondary ID [1] 313116 0
Sponsor Protocol Number: AB-WIN-001
Universal Trial Number (UTN)
Trial acronym
WIN Study
Linked study record
This study is an expansion of the study: ACTRN12623000675628 Initial Group.

Health condition
Health condition(s) or problem(s) studied:
Pelvic Pain 335376 0
Dysmenorrhoea 335377 0
Reproductive Health and Childbirth 335378 0
Condition category
Condition code
Reproductive Health and Childbirth 331952 331952 0 0
Menstruation and menopause
Reproductive Health and Childbirth 331953 331953 0 0
Contraception

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Alyra intrauterine device – contains ~37mg of levonorgestrel releasing approximately 9.6 micrograms per 24 hours and ~27 mg of amitriptyline releasing approximately 0.35 mg per 24 hours. The device will be inserted by a specialist Gynaecologist highly experienced in the placement of IUDs in the general population. The Alyra intrauterine device is placed in exactly the same way, and by the same procedures and practices, as that with a standard Mirena 'Trademark' device. Only study approved Gynaecologists are able to place the Alyra device. The total duration of IUD placement is 90 days (~ 3 months). Throughout the duration of the study, you will attend onsite visits for frequent safety and monitoring checks. These checks will ensure that the device is positioned correctly and are designed to answer any queries that you may have as the study arises. You will also be given a participant information card containing the contact details of your study Gynaecologists, should you need to contact them at any time in regard to your study IUD. Following insertion of the device, participants will complete a daily study specific APP to monitor their
experiences of the device.
Intervention code [1] 329694 0
Prevention
Intervention code [2] 329695 0
Treatment: Devices
Intervention code [3] 329696 0
Treatment: Drugs
Comparator / control treatment
This study will investigate the Alyra device compared with the currently approved TGA standard Mirena 'Trademark' IUD as a market comparator. The Mirena device releases levonorgestrel (a progesterone hormone) as a component of the contraceptive method. In this device levonorgestrel is released at 20 micrograms into the uterine cavity per 24 hours following insertion. Following insertion of the Mirena devices, participants will complete a
daily study specific APP to monitor their experiences of the device. As this device is the comparator, it will also be monitored for the drug release rate levels of levonorgestrel, over 90 days (~ 3 months).
Control group
Active

Outcomes
Primary outcome [1] 339558 0
Among participants with pre-existing dysmenorrhea-related pelvic pain, the objectives of this study are as follows: To investigate and expand knowledge of the pharmacokinetic profile of amitriptyline release for the Alyra Device through investigation of a larger number of participants
Timepoint [1] 339558 0
PK samples will be collected and compared at 1 hour post-device insertion, then again on day 7, 14, 30 and 90, after intervention commencement.
Primary outcome [2] 339560 0
To investigate and expand knowledge of the pharmacokinetic profile of levonorgestrel release for the Alyra Device through investigation of a larger number of participants
Timepoint [2] 339560 0
PK samples will be collected and compared at 1 hour post-device insertion, then again on day 7, 14, 30 and 90, after intervention commencement.
Primary outcome [3] 339630 0
To compare the frequency of treatment emergent adverse events (TEAEs) between treatments
Timepoint [3] 339630 0
From day 0, the day of device insertion, until 90 days post-device insertion.
Secondary outcome [1] 440430 0
To establish the expected number of days of bleeding following insertion of the Alyra Device to guide future studies
Timepoint [1] 440430 0
Baseline screening period (up to 30 days before device insertion) compared to 30, 60 and 90 days post-device insertion.
Secondary outcome [2] 440431 0
To investigate the number of days of pelvic pain experienced in each 3 subsequent 30-day time periods (90 days in total) with the number of days of pain experienced in the 30 days prior to device insertion to guide future studies
Timepoint [2] 440431 0
Baseline screening period (30 days before device insertion) compared to 30, 60 and 90 days post-device insertion.
Secondary outcome [3] 440678 0
To investigate and expand knowledge of the pharmacokinetic profile of nortriptyline release for the Alyra Device through investigation of a larger number of participants
Timepoint [3] 440678 0
PK samples will be collected and compared at 1 hour post-device insertion, then again on day 7, 14, 30 and 90 after intervention commencement.
Secondary outcome [4] 440690 0
To investigate the intensity of pain experienced in each 3 subsequent 30-day time periods (90 days in total) with the number of days of pain experienced in the 30 days prior to device insertion to guide future studies
Timepoint [4] 440690 0
Baseline screening period (30 days before device insertion) compared to 30, 60 and 90 days post-device insertion.

Eligibility
Key inclusion criteria
*Is in good general health.
*Agrees to have an IUD for ~90 days
*Agrees to take oral temperature recordings when required
*Has a history of regular menstrual cycles (i.e. every 21-35 days)
*Has a uterus with no significant abnormalities
*Agrees to record their symptoms daily and use of medications on a study specific APP
*Does not plan to become pregnant during their study involvement
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Know sensitivity, intolerance, or allergy to non-steroidal anti-inflammatory drugs, paracetamol, ibuprofen, levonorgestrel, amitriptyline, or any components of the intrauterine device
*Has a positive urine drug screen
*Has a significant gynaecological condition
*Has undergone a hysterectomy or bilateral oophorectomy
*Has recurrent or current pelvic infections
*Has severe arterial disease
*Has uncontrolled epilepsy
*Severe Endometriosis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e., computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Pharmacokinetics:
Plasma amitriptyline, nortriptyline and levonorgestrel parameters to be analysed as: Cmax, tmax, AUC0-last, Cav.
Participant Tolerability Outcomes:
Mixed model for repeated measure (MMRM) analyses to compare the change from baseline over the treatment period between the two treatment groups for the following:
- number of days of pelvic pain reported per 30-day time periods post device insertion at 30, 60 and 90 days
- average daily severity of pelvic pain (derived from days when pain was reported) for each of the three 30-day time periods post insertion.
- number of days of uterine bleeding/spotting per 30 days time periods post insertion.
- pelvic pain AUC30day for each of the three 30-day time periods post insertion.
The model for each parameter will include treatment, time (30, 60 and 90 days) and an interaction between treatment and time, as fixed effects baseline values as a covariate and subject as a random effect. Treatment differences will be estimated using least square means difference and 95% two-sided confidence intervals. The treatment effect will be estimated for each timepoints as well as the overall study period, with the same weight applied to the treatment effects for each timepoints.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/12/2024
Actual
Date of last participant enrolment
Anticipated
31/10/2025
Actual
Date of last data collection
Anticipated
28/02/2026
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 27183 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 43266 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 317561 0
Commercial sector/Industry
Name [1] 317561 0
CUREator Grant Funding
Country [1] 317561 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Alyra Biotech Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 319865 0
None
Name [1] 319865 0
Address [1] 319865 0
Country [1] 319865 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316272 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 316272 0
Ethics committee country [1] 316272 0
Australia
Date submitted for ethics approval [1] 316272 0
24/10/2022
Approval date [1] 316272 0
17/02/2023
Ethics approval number [1] 316272 0
2022/HRE00231

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137350 0
Prof Louise Hull
Address 137350 0
PARC Clinical Research, Level 4C Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 137350 0
Australia
Phone 137350 0
+61 403 993 312
Fax 137350 0
Email 137350 0
louise.hull@adelaide.edu.au
Contact person for public queries
Name 137351 0
Rachael Tippett
Address 137351 0
Alyra Biotech Pty Ltd, 5 Hauteville Terrace, Eastwood, Adelaide, South Australia, 5063
Country 137351 0
Australia
Phone 137351 0
+61 414 334 583
Fax 137351 0
Email 137351 0
rachael.tippett@alyrabiotech.com
Contact person for scientific queries
Name 137352 0
Prof Louise Hull
Address 137352 0
PARC Clinical Research, Level 4C Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 137352 0
Australia
Phone 137352 0
+61 403 993 312
Fax 137352 0
Email 137352 0
louise.hull@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study is sponsored research and the privacy of the product must be maintained.


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.