First in woman safety and ease of use assessment of 400 mg progesterone Callavid in women with luteal phase progesterone insufficiency
| ISRCTN | ISRCTN82163970 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82163970 |
| ClinicalTrials.gov (NCT) | NCT07136922 |
| Integrated Research Application System (IRAS) | 1008895 |
| Protocol serial number | SQ641924 |
| Sponsor | University Hospitals Coventry and Warwickshire NHS Trust |
| Funder | National Institute for Health and Care Research |
- Submission date
- 15/11/2025
- Registration date
- 11/02/2026
- Last edited
- 11/02/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
This is a Phase I, first-in-human randomised control trial to assess the safety of a new vaginal 400 mg progesterone drug-device combination product called 400 mg progesterone Callavid.
Who can participate?
Women aged 18 to 45 years who have had at least one miscarriage and have luteal phase progesterone insufficiency
What does the study involve?
400 mg Progesterone Callavid and 400 mg Cyclogest are used vaginally twice a day for 7 days in each round.
Participants are randomly allocated to one of two groups.
Group 1: Participants use Callavid first for 2-hour wear before crossing over to use Cyclogest. In the third round, participants receive Callavid again but for 3-hour wear.
Group 2: Participants use Cyclogest first before crossing over to use Callavid for 2 hour wear. In the third round, participants receive Callavid again but for 3-hour wear.
What are the possible benefits and risks of participating?
Known common side effects of vaginally administered progesterone are vaginal discharge, bloating and breast tenderness, and mood changes (more rare). In some people, taking progesterone can alter the length of the menstrual cycle, though this is not very common.
Potential risks of contact with the device component of the novel drug-device combination IMP 400 mg progesterone Callavid have been extensively assessed in the Biological Evaluation Plan and will be thoroughly analysed within the Biological Evaluation Report, which will be submitted by the sponsor to MHRA and REC for review. The drug formulation uses established active and excipient ingredients, the safety profile of which are detailed in the IMPD.
If the novel drug-device combination IMP 400 mg progesterone Callavid delivers less progesterone than does the standard of care Cyclogest 400 mg reference IMP, then the patient may have a lower probability of successfully conceiving during the single affected menstrual cycle.
During the interview, participants may become embarrassed or upset by some of the question topics. We have drafted a distress protocol to enable the researchers to help anyone who may need it.
Attending hospital for 6 hours on up to 6 occasions throughout the trial represents a burden for participants. We have attempted to minimise this by offering compensation as well as childcare costs, if required.
Where is the study run from?
University Hospitals Coventry and Warwickshire NHS Trust (UK)
When is the study starting and how long is it expected to run for?
January to August 2026
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
freedom.studyoffice@uhcw.nhs.uk
Contact information
Public
Trial Management Unit
University Hospital Coventry
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
| Phone | +44 (0)2476 966197 |
|---|---|
| freedomstudyoffice@uhcw.nhs.uk |
Scientific
Charles House
108-110 Finchley Road
London
NW3 5JJ
United Kingdom
| Phone | +44 (0)20 77545400 |
|---|---|
| clinicaltrials@callali.ly |
Principal investigator
Clinical Sciences Research Laboratories
University Hospitals Coventry and Warwickshire NHS Trust
Coventry
CV2 2DX
United Kingdom
| Phone | +44 (0)2476 964000 |
|---|---|
| s.quenby@warwick.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Open randomized controlled cross over trial |
| Secondary study design | Randomised cross over trial |
| Scientific title | First in woman safety and ease of use assessment of 400 mg progesterone Callavid in women with luteal phase progesterone insufficiency |
| Study acronym | FREEDOM |
| Study objectives | Primary objective: To establish the safety of 400 mg progesterone Callavid, a new drug-device combination product that is delivered vaginally. Secondary objectives: 1. To explore the usability and acceptability to patients of 400 mg progesterone Callavid, and Cyclogest 400 mg (standard care) 2. To assess the delivery of vaginal progesterone into the blood using 400 mg progesterone Callavid with 2-hour wear (round 1 or 2) and 3-hour wear (round 3), and Cyclogest 400 mg (standard care) |
| Ethics approval(s) |
Not yet submitted |
| Health condition(s) or problem(s) studied | Women who have had at least one miscarriage and have luteal phase progesterone insufficiency |
| Intervention | IMP is 400 mg Progesterone Callavid used vaginally 2 x day for 7 days in each round. Comparator is 400mg Cyclogest used vaginally 2 x day for 7 days in each round. Arm 1: Callavid 2-hour first , Cyclogest second, Callavid 3-hour third Participants are randomised to use Callavid first for 2-hour wear before crossing over to use Cyclogest. In the third round, participants receive Callavid again but for 3-hour wear. Arm 2: Cyclogest first, Callavid 2-hour second, Callavid 3-hour third Participants are randomised to use Cyclogest first before crossing over to use Callavid for 2 hour wear. In the third round, participants receive Callavid again but for 3-hour wear. Randomisation will be conducted by UHCW Pharmacy. |
| Intervention type | Drug |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Callavid (progesterone) , Cyclogest (progesterone) |
| Primary outcome measure(s) |
Any grade of adverse event (AE), specifically allergy, gastrointestinal (bloating, constipation), neurological (headache, drowsiness, euphoria), according to Common Terminology Criteria for Adverse Events (CTCAE), up to 24 hours after the last dose at each trial round |
| Key secondary outcome measure(s) |
1. Level of fear/anxiety measured by PROMIS short 4-item anxiety-fear instrument completed on day 1 and day 7 during rounds 1, 2 and 3 of treatment |
| Completion date | 30/08/2026 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Female |
| Target sample size at registration | 20 |
| Key inclusion criteria | 1. Female sex 2. Clinical diagnosis of luteal phase insufficiency on the basis of one of the following: 2.1. Spotting before first day of heavy menstrual bleeding 2.2. Short time between ovulation and menstruation 2.3. Symptoms of progesterone insufficiency 3. Aged 18 – 45 years 4. Experienced at least one previous miscarriage |
| Key exclusion criteria | 1. Positive pregnancy test 2. Currently breastfeeding 3. Allergies or contraindications to excipients/ progesterone pessaries 4. Current or history of previous condition where hormone treatments are contraindicated, e.g. breast cancer 5. Individuals who lack capacity to consent to the trial 6. Individuals who have an inability to comply with the trial procedures (e.g. cannot attend hospital for trial visits) 7. Inability to understand English |
| Date of first enrolment | 01/02/2026 |
| Date of final enrolment | 30/08/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Coventry
CV2 2DX
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan |
Editorial Notes
11/02/2026: ISRCTN received notification of combined HRA/MHRA approval for this trial on 11/02/2026.
17/11/2025: Study's existence confirmed by the HRA.
