Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001763831p
Ethics application status
Not yet submitted
Date submitted
30/11/2021
Date registered
23/12/2021
Date last updated
23/12/2021
Date data sharing statement initially provided
23/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Modelling of allopregnanolone concentrations after multiple dose administration of progesterone.
Scientific title
Pharmacokinetics of allopregnenolone after multiple dose administration of progesterone: confirmation of modelled data.
Secondary ID [1] 305889 0
None
Universal Trial Number (UTN)
Trial acronym
PAMP (Pharmacokinetics of Allopregnanolone Multiple Progesterone)
Linked study record
This is a follow-up of study ACTRN12620001102965.

Health condition
Health condition(s) or problem(s) studied:
Post Partum Depression 324438 0
Condition category
Condition code
Mental Health 321933 321933 0 0
Depression
Reproductive Health and Childbirth 322227 322227 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Open label multiple dose pharmacokinetic and safety study to measure plasma ALLO concentrations after repeat doses of extended release progesterone oral capsules given 8 hourly, over 40 hours.
Dosing with progesterone 100mg capsules every 8 hours as follows:
8AM 0 hours: 200mg
4PM 8 hours: 100mg
12MN 16 hours: 100mg
8AM 24 hours: 100mg
4PM 32 hours: 100mg
12MN 40 hours: 100mg
Intervention code [1] 322294 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329704 0
plasma ALLO concentrations between 0-48 hours after 8-hourly dosing with extended release progesterone capsules.
Timepoint [1] 329704 0
We will extract plasma samples to measure plasma progesterone and allopregnenolone concentrations at the following times: predose and 8, 24, 32, and 48 hours.
Secondary outcome [1] 403547 0
To assess the safety and tolerability of extended release progesterone capsules in healthy volunteers:
Vital signs and adverse events will be used to assess safety and tolerability throughout the study. Tolerability will be assessed by: reported adverse events throughout study.

Throughout the study, the general well-being of the participants will be sought and any adverse events will be recorded and investigated.

Safety data will be monitored for at least 2 hours after the first dose of progesterone. Adverse events will be monitored throughout the study. Safety data will consist of a baseline assessment of general well-being, including systems enquiry, vital signs (blood pressure, heart rate, and temperature). Tolerability assessments include reported adverse events throughout study.

Timepoint [1] 403547 0
Throughout the study, the general well-being of the participants will be sought and any adverse events will be recorded and investigated.

Safety data will be monitored for at least 2 hours after the first dose of progesterone. Safety data will consist of a baseline assessment of general well-being, including systems enquiry, vital signs (blood pressure, heart rate, and temperature). Tolerability assessments include reported adverse events throughout study.
Adverse events will be monitored throughout the study. This will be accomplished by direct questioning and report by participants once daily throughout the study.

Eligibility
Key inclusion criteria
1. Capable of understanding and signing an informed consent
2. Males: aged 18-65 years
3. Females: post-menopausal, aged 50-65 years.
4. Weight at least 50kg, with a minimum BMI of 18.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Female participants who are not post-menopausal
2. Participants who, in the opinion of the investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
3. Any participant for whom the investigator believes, for any reason, that participation would not be an acceptable risk.
4. Participants with severe acute or chronic medical illnesses.
5. Participants who regularly use alcohol or recreational drugs.
6. Participants using HRT

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)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
STATISTICAL PLAN
Participant Population
The Evaluable Participant Population (EPP) will be defined as all participants who receive at least one dose of progesterone. The primary population for the evaluation of study objectives in this trial will be the EPP population.

Observational Period
The observational period for the study will be from participant entry until 48 hours

Statistical Analyses
Participant demographics, background characteristics and trial data (safety, vital signs, pharmacokinetics) will be descriptively summarized for all subjects. The relationship between sedation VAS ratings and ALLO concentrations will be explored using regression methods.

Statistical Power Calculation
The sample size is chosen pragmatically and not based on any statistical power considerations.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/01/2022
Actual
Date of last participant enrolment
Anticipated
12/12/2022
Actual
Date of last data collection
Anticipated
15/12/2022
Actual
Sample size
Target
8
Accrual to date
Final
Recruitment outside Australia
Country [1] 24358 0
New Zealand
State/province [1] 24358 0
Otago

Funding & Sponsors
Funding source category [1] 310238 0
Other Collaborative groups
Name [1] 310238 0
Royal Australian New Zealand College of Psychiatry
Country [1] 310238 0
Australia
Primary sponsor type
University
Name
University of Otago, Dunedin, New Zealand.
Address
362 Leith Street, North Dunedin, Dunedin 9016.
New Zealand.
Country
New Zealand
Secondary sponsor category [1] 311382 0
None
Name [1] 311382 0
Address [1] 311382 0
Country [1] 311382 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 309917 0
Health and Disability Ethics Committees (HDECs), New Zealand
Ethics committee address [1] 309917 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140.
New Zealand.
Ethics committee country [1] 309917 0
New Zealand
Date submitted for ethics approval [1] 309917 0
28/12/2021
Approval date [1] 309917 0
Ethics approval number [1] 309917 0

Summary
Brief summary
Postpartum depression (PPD) is a severe disorder that adversely impacts both mothers and infants and is associated with significant morbidity and mortality. PPD’s pathophysiology may involve changes in perinatal hormones such as allopregnanolone (ALLO, an endogenous progesterone metabolite). Brexanolone (BREX) is a small molecule, neuroactive steroid GABAA receptor allosteric modulator consisting of synthetic ALLO and a solubilizing agent. In early 2019 BREX received FDA approval for the treatment of PPD. BREX is only available through a restricted program and is expensive. We explored whether ALLO concentrations could be increased via oral progesterone loading.

We have now completed a Phase 1 pharmacokinetic study to evaluate plasma ALLO concentration-time profiles after oral dosing of progesterone (20/CEN/205), and have modelled this to identify a dosage regimen which will give plasma ALLO concentrations similar to those seen at the end of pregnancy (~50ng/mL). The objective of this study is to collect and analyze plasma ALLO samples in healthy volunteers on this dosage regiment, to confirm accuracy of this model.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115826 0
A/Prof Yoram Barak
Address 115826 0
Department of Psychological Medicine.
School of Medicine.
464 Cumberland Street.
Dunedin. 9054
New Zealand.
Country 115826 0
New Zealand
Phone 115826 0
+64347409451
Fax 115826 0
Email 115826 0
Yoram.Barak@otago.ac.nz
Contact person for public queries
Name 115827 0
A/Prof Yoram Barak
Address 115827 0
Department of Psychological Medicine.
School of Medicine.
464 Cumberland Street.
Dunedin. 9054
New Zealand.
Country 115827 0
New Zealand
Phone 115827 0
+64347409451
Fax 115827 0
Email 115827 0
Yoram.Barak@otago.ac.nz
Contact person for scientific queries
Name 115828 0
A/Prof Yoram Barak
Address 115828 0
Department of Psychological Medicine.
School of Medicine.
464 Cumberland Street.
Dunedin. 9054
New Zealand.
Country 115828 0
New Zealand
Phone 115828 0
+64347409451
Fax 115828 0
Email 115828 0
Yoram.Barak@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All data
When will data be available (start and end dates)?
Data will be available from recruitment of first participant. This is expected in Q1 2022.
Data will be available for 7 years after publication.
Available to whom?
Anyone
Available for what types of analyses?
Any
How or where can data be obtained?
Email the principal investigator:
Yoram.Barak@otago.ac.nz


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14286Study protocol  Yoram.Barak@otago.ac.nz 383192-(Uploaded-30-11-2021-10-37-56)-Study-related document.docx



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.