Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001102965p
Ethics application status
Submitted, not yet approved
Date submitted
18/06/2020
Date registered
23/10/2020
Date last updated
23/10/2020
Date data sharing statement initially provided
23/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetics of allopregnanolone after multiple dose administration of progesterone in post-menopausal healthy volunteer women.
Scientific title
Pharmacokinetics of allopregnanolone after multiple dose administration of progesterone in post-menopausal healthy volunteer women.
Secondary ID [1] 301528 0
RANCPsychiatry: 1699
Universal Trial Number (UTN)
Trial acronym
Linked study record
NA.

Health condition
Health condition(s) or problem(s) studied:
Post Partum Depression 317884 0
Postnatal care. 318272 0
Condition category
Condition code
Mental Health 315925 315925 0 0
Depression
Reproductive Health and Childbirth 316616 316616 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Multiple rising dose study to measure plasma allopregnanolone concentrations after multiple doses of extended release progesterone tablets.

Cohort 1 will take a 300mg dose twice on Day 1, once in the morning and afternoon, followed by a single 600mg dose in the morning on Day 2.
Cohort 2 will take a 300mg dose once on Day 1, in the morning, 600 mg dose once on Day 1, in the afternoon, followed by a single 900mg dose in the morning on Day 2.
Cohort 3 will take a 300mg dose once on Day 1, in the morning, 900 mg dose once on Day 1, in the afternoon, followed by a single 1200mg dose in the morning on Day 2.

Adherence will be indirectly monitored by the serum levels testing of allopregnenolone.

Participants can participate in only one of the 3 cohorts.
Cohorts will start simultaneously.
Intervention code [1] 317854 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324166 0
The primary endpoint will be peak allopregnenolone concentrations on Day 2,of the multiple dosing schedule.
Plasma samples will be assayed using a validated ELISA method. Pharmacokinetics will be analysed using standard non-compartmental methods.
Non-compartmental pharmacokinetics analysis is highly dependent on estimation of total drug exposure. Total drug exposure will be estimated by area under the curve (AUC) methods, with the trapezoidal rule (numerical integration).
To complement the ELISA method combined liquid chromatography-tandem mass spectroscopy analysis of progesterone metabolites (LC-MS/MS) will be used.
Timepoint [1] 324166 0
Primary: 8 hours post Day 2 morning dose.
Additional: Plasma samples to measure plasma progesterone and allopregnenolone concentrations, pre-dose and 2, 4, 6 and 8 hours post Day 2 morning dose.
Primary outcome [2] 324474 0
Assessment of dose-proportionality.
The concentration of progesterone and allopregnanolone will be calculated on the basis of standard curves. Calibration curves will be constructed from seven concentrations, covering the range from 2 ng/mL to 500 ng/mL.
Timepoint [2] 324474 0
Primary: 8 hours post Day 2 morning dose.
Additional: Plasma samples to measure plasma progesterone and allopregnenolone concentrations, pre-dose and 2, 4, 6 and 8 hours post Day 2 morning dose.
Secondary outcome [1] 383893 0
Safety assessed using vital signs and adverse events.
Vital signs: blood pressure, pulse and temperature will be measured using standard equipment.
Adverse Events: the most common AEs expected with progesterone are: chills, cough or hoarseness. These will be monitored by the standardized FDA AEs reporting form
Timepoint [1] 383893 0
Vital signs will be assessed predose and 2 hours post AM and 2 hours post PM Day 1 dos. Also, vital signs will be assessed predose and 2,4,6 and 8 hours post Day 2 morning dose.
Adverse Events reporting form will be completed on the morning of Day 2, morning of Day 3 and morning of day 9 (one week after completion of trial).

Eligibility
Key inclusion criteria
Healthy females; aged 20-60; weight at least 50kg, with a minimum BMI of 18.
Participants will be POST menopausal as we are seeking healthy volunteers who are physiologically not producing endogenous progesterone.
Minimum age
20 Years
Maximum age
60 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe or unstable medical conditions; regular use of alcohol/ recreational drugs.

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)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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
Number of Participants
Up to 24 female participants aged > 65 years will be enrolled in this study. Participants will be recruited from the general public in Dunedin. This is a convenience sample based on previous studies recruiting in a similar manner.
Demographic and Background Characteristics: Summary statistics will be calculated and reported for demographic, vital signs, and AEs data. Categorical variables will be reported using counts and percentages. In order to accommodate the repeated measures on participants from the multiple doses received by each participant iinear mixed models will be used along with fixed effects for time and dose.
As this is an exploratory study, and to avoid reducing power to detect both beneficial and adverse effects, no adjustments for multiple comparisons will be made.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/11/2020
Actual
Date of last participant enrolment
Anticipated
30/04/2021
Actual
Date of last data collection
Anticipated
3/05/2021
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 22678 0
New Zealand
State/province [1] 22678 0
Otago

Funding & Sponsors
Funding source category [1] 305968 0
Other
Name [1] 305968 0
Royal Australian New Zealand College of Psychiatry
Country [1] 305968 0
Australia
Primary sponsor type
Other
Name
Royal Australian New Zealand College of Psychiatry
Address
RANZCP Head Office
309 La Trobe Street
Melbourne VIC 3000
Australia
Country
Australia
Secondary sponsor category [1] 306426 0
None
Name [1] 306426 0
Address [1] 306426 0
Country [1] 306426 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 306208 0
NZ Central Health and Disability Ethics Committee
Ethics committee address [1] 306208 0
Ethics committee country [1] 306208 0
New Zealand
Date submitted for ethics approval [1] 306208 0
01/10/2020
Approval date [1] 306208 0
Ethics approval number [1] 306208 0

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

Contacts
Principal investigator
Name 103098 0
A/Prof Yoram Barak
Address 103098 0
University of Otago.
PO Box 56
Dunedin 9054.
Country 103098 0
New Zealand
Phone 103098 0
+6434740999
Fax 103098 0
+6434709684
Email 103098 0
[email protected]
Contact person for public queries
Name 103099 0
Yoram Barak
Address 103099 0
University of Otago.
PO Box 56
Dunedin 9054.
Country 103099 0
New Zealand
Phone 103099 0
+6434740999
Fax 103099 0
+6434709684
Email 103099 0
[email protected]
Contact person for scientific queries
Name 103100 0
Yoram Barak
Address 103100 0
University of Otago.
PO Box 56
Dunedin 9054.
Country 103100 0
New Zealand
Phone 103100 0
+6434740999
Fax 103100 0
+6434709684
Email 103100 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
Only unidentified clustered data will be available.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
8260Study protocol  [email protected] 380010-(Uploaded-17-07-2020-14-01-50)-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.