Luteal Phase Insuffiency, Progesterone Delivery
Conditions
Keywords
progesterone delivery, progesterone, vaginal drug delivery, callavid, cyclogest, women's health
Brief summary
The aim of this clinical trial is to assess safety of a new vaginal 400mg progesterone drug-device combination product in a first in human trial. Additionally, it aims to assess user acceptability and ability to deliver progesterone. This Phase I trial is a randomised open-label first-in-human crossover trial, recruiting participants who are non-pregnant with luteal phase insufficiency. The main questions it aims to answer are: 1. What are the safety and tolerability profiles of the two progesterone formulations (400mg Progesterone Callavid vs. Cyclogest 400 mg), including the incidence of adverse events (if any) such as allergic reactions, gastrointestinal symptoms (e.g. bloating, constipation), and neurological effects (e.g. headache, drowsiness, euphoria)? 2. What is usability experience for patients using the Callavid drug-device combination compared to pessaries / suppositories (i.e. Cyclogest 400 mg)? 3. How do serum progesterone levels vary within participants when using 400 mg progesterone delivered via the Callavid drug-device combination compared to Cyclogest 400 mg, and what are the implications of this variability for dose-response relationships and future trial design?
Interventions
COMBINATION_PRODUCT400mg progesterone Callavid - 2hr wear
400mg progesterone Callavid, 2 hour wear, twice daily for 7 days
DRUGCyclogest 400 mg
Cyclogest 400 mg pessary, twice daily for 7 days
COMBINATION_PRODUCT400mg progesterone Callavid - 3hr wear
400mg progesterone Callavid, 3 hour wear, twice daily for 7 days
Sponsors
Calla Lily Clinical Care Ltd
University Hospitals Coventry and Warwickshire NHS Trust
University of Warwick
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The trial consists of three rounds, conducted over three consecutive menstrual cycles. Participants are randomised to receive either Cyclogest 400mg progesterone pessary in the first round, crossing over to 400mg progesterone Callavid (administered for 2 hours) in the second round, or 400mg progesterone Callavid (administered for 2 hours) in the first round crossing over to Cyclogest 400mg progesterone pessary in the second round. The third round is to investigate the safety of 400mg progesterone Callavid when administered for 3 hours. This would inform us on the safety of the additional hour of wear time. Each arm will complete the third round following the first two crossover rounds.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Female sex * Clinical diagnosis of luteal phase insufficiency on the basis of one of the following: * Spotting before first day of heavy menstrual bleeding * Short time between ovulation and menstruation * Symptoms of progesterone insufficiency * Aged 18 - 45 years * Experienced at least one previous miscarriage
Exclusion criteria
* Positive pregnancy test * Currently breastfeeding * Allergies or contraindications to excipients / progesterone pessaries * Current or history of previous condition where hormone treatments are contraindicated e.g. breast cancer * Individuals who lack capacity to consent to the trial * Individuals who have an inability to comply with the trial procedures (e.g. cannot attend hospital for trial visits) * Inability to understand English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events recorded from 400 mg progesterone Callavid | From treatment up to 24 hours after the last dose | Any grade of adverse events, specifically allergy, gastrointestinal (bloating, constipation), neurological (headache, drowsiness, euphoria) according to Common Terminology Criteria for Adverse Events (CTCAE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PROMIS Anxiety questionnaire | Day 1 and day 7 of treatment in each round (3 rounds total) | PROMIS short 4-item anxiety fear instrument |
| Acceptability questionnaires | Day 1 and day 7 of treatment in each round (3 rounds total) | User acceptability questionnaires on 400mg progesterone Callavid |
| Semi-structured user experience interviews | day 7 | Semi-structured interviews with participants after completion of the crossover rounds. |
| Delivery of vaginal progesterone into the blood at 2 hour and 3 hour wear | Multiple time points on Day 1 and Day 7 of each treatment | The serum progesterone levels at time 0, 3- and 6-hour after the first dose on day 1 and the thirteenth dose which is on day 7 each round of treatment are measured. Progesterone levels are measured for both 400 mg progesterone Callavid and 400 mg Cyclogest. |
Countries
United Kingdom
Contacts
CONTACTSiobhan Quenby
Outcome results
None listed