First in Human Safety and Ease of Use Assessment of 400mg Progesterone Callavid in Women With Luteal Phase Insufficiency (FREEDOM)

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?

Study Overview

• Status: Recruiting
• Conditions: Luteal Phase Insuffiency; Progesterone Delivery
• Intervention / Treatment: Combination product: 400mg progesterone Callavid - 2hr wear; Drug: Cyclogest 400 mg; Combination product: 400mg progesterone Callavid - 3hr wear

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Siobhan Quenby; Phone Number: +442476964000; Email: s.quenby@warwick.ac.uk

Study Locations

• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • Recruiting
    • University Hospitals Coventry & Warwickshire NHS Trust
    • Contact: Violet Matthews Trial Manager; Phone Number: +44 2476 966197; Email: freedomstudyoffice@uhcw.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Callavid 2-hr first, Cyclogest second, Callavid 3-hr 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.	Combination product: 400mg progesterone Callavid - 2hr wear; 400mg progesterone Callavid, 2 hour wear, twice daily for 7 days; Drug: Cyclogest 400 mg; Cyclogest 400 mg pessary, twice daily for 7 days; Combination product: 400mg progesterone Callavid - 3hr wear; 400mg progesterone Callavid, 3 hour wear, twice daily for 7 days
Active Comparator: Cyclogest first, Callavid 2-hr second, Callavid 3-hr 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.	Combination product: 400mg progesterone Callavid - 2hr wear; 400mg progesterone Callavid, 2 hour wear, twice daily for 7 days; Drug: Cyclogest 400 mg; Cyclogest 400 mg pessary, twice daily for 7 days; Combination product: 400mg progesterone Callavid - 3hr wear; 400mg progesterone Callavid, 3 hour wear, twice daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events recorded from 400 mg progesterone Callavid	Any grade of adverse events, specifically allergy, gastrointestinal (bloating, constipation), neurological (headache, drowsiness, euphoria) according to Common Terminology Criteria for Adverse Events (CTCAE).	From treatment up to 24 hours after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Anxiety questionnaire	PROMIS short 4-item anxiety fear instrument	Day 1 and day 7 of treatment in each round (3 rounds total)
Acceptability questionnaires	User acceptability questionnaires on 400mg progesterone Callavid	Day 1 and day 7 of treatment in each round (3 rounds total)
Semi-structured user experience interviews	Semi-structured interviews with participants after completion of the crossover rounds.	day 7
Delivery of vaginal progesterone into the blood at 2 hour and 3 hour wear	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.	Multiple time points on Day 1 and Day 7 of each treatment

Collaborators and Investigators

• Sponsor: Calla Lily Clinical Care Ltd
• Collaborators: University of Warwick; University Hospitals Coventry and Warwickshire NHS Trust

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: July 28, 2025
• First Submitted That Met QC Criteria: August 21, 2025
• First Posted (Actual): August 22, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: progesterone; women's health; progesterone delivery; vaginal drug delivery; callavid; cyclogest
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Gonadal Steroid Hormones; Gonadal Hormones; Pregnenediones; Pregnenes; Corpus Luteum Hormones; Progesterone Congeners; Progesterone
• Other Study ID Numbers: SQ641924

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No