Modelling of allopregnanolone concentrations after multiple dose administration of progesterone.

Pharmacokinetics of allopregnenolone after multiple dose administration of progesterone: confirmation of modelled data.

Status

Withdrawn

Phases

Phase 2

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12621001763831

Acronym

PAMP (Pharmacokinetics of Allopregnanolone Multiple Progesterone)

Enrollment

Registered

2021-12-23

Start date

2022-01-17

Completion date

2022-12-12

Last updated

2025-01-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

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.

Interventions

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

Study design

Allocation

Non-randomised trial

Intervention model

Single group

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

18 Years to 65 Years

Healthy volunteers

Yes

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.

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

Outcome results