Uterine Myomas
Conditions
Brief summary
This trial will assess the efficacy and safety of PGL4001 with concomitant iron administration versus placebo with concomitant iron administration, over a 3-month period for the pre-operative treatment of pre-menopausal women suffering from excessive uterine bleeding due to uterine myoma.
Interventions
DRUGPGL4001 (ulipristal) and iron
tablets
DRUGPGL4001 matching placebo and iron
tablets
Sponsors
PregLem SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Be a pre-menopausal woman between 18 and 50 years inclusive. * Have excessive uterine bleeding due to myoma. * Have a myoma-related anaemia. * Have a myomatous uterus with at least one myoma of ≥ 3 cm diameter in size. * Be eligible for one surgical procedure: e.g. hysterectomy, myomectomy or others. * If of childbearing potential the subject must be practicing a non-hormonal method of contraception. * Have a Body Mass Index (BMI) ≥ 18 and ≤ 40.
Exclusion criteria
* Has a history of or current uterine, cervical, ovarian or breast cancer. * Has a history of or current endometrium atypical hyperplasia. * Has a known severe coagulation disorder. * Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRH-agonist. * Has abnormal hepatic function at study entry. * Has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study. * Has a current (within twelve months) problem with alcohol or drug abuse. * Is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13) | Week 13 visit | Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Patients recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Monthly scores range from 0 (amenorrhea) to more than 500, with higher numbers indicating more bleeding. A slightly stained tampon/towel scores 1, a partially stained tampon/towel scores 5, a completely saturated tampon scores 10 and a completely saturated towel scores 20. Small clots/flooding (2cm) score 1. Large clots/flooding (3cm) score 5. Menorrhagia is defined as a PBAC \> 100 during one menstrual period which approximates to a blood loss of \> 80 mL. A PBAC of 400 corresponds to a blood loss of around 300 mL or approximately 80 tampons/towels used. The week 13 PBAC score was calculated using the last 28 days of treatment. |
| Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit) | Week 13 | Percent change in total fibroid volume from screening to end of treatment visit (Week 13 visit) assessed by MRI and read centrally by a radiologist who was unaware of the study-group assignments. The total fibroid volume was the sum of the individual fibroid volumes. |
Countries
Czechia, Hungary, India, Romania, Russia, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A (PGL4001 5mg) PGL4001 5 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ | 95 |
| B (PGL4001 10mg) PGL4001 10 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ | 98 |
| C (Placebo) PGL4001 matching placebo (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ | 48 |
| Total | 241 |
Baseline characteristics
| Characteristic | A (PGL4001 5mg) | B (PGL4001 10mg) | C (Placebo) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 95 Participants | 98 Participants | 48 Participants | 241 Participants |
| Age Continuous | 41.2 years STANDARD_DEVIATION 5.9 | 42.0 years STANDARD_DEVIATION 5.5 | 41.6 years STANDARD_DEVIATION 5.6 | 41.6 years STANDARD_DEVIATION 5.7 |
| Region of Enrollment Czech Republic | 7 participants | 6 participants | 3 participants | 16 participants |
| Region of Enrollment Hungary | 7 participants | 11 participants | 9 participants | 27 participants |
| Region of Enrollment India | 10 participants | 11 participants | 7 participants | 28 participants |
| Region of Enrollment Romania | 17 participants | 17 participants | 8 participants | 42 participants |
| Region of Enrollment Russian Federation | 28 participants | 19 participants | 13 participants | 60 participants |
| Region of Enrollment Ukraine | 26 participants | 34 participants | 8 participants | 68 participants |
| Sex: Female, Male Female | 95 Participants | 98 Participants | 48 Participants | 241 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 95 | 52 / 98 | 22 / 48 |
| serious Total, serious adverse events | 2 / 95 | 1 / 98 | 2 / 48 |
Outcome results
Primary
Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13)
Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Patients recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Monthly scores range from 0 (amenorrhea) to more than 500, with higher numbers indicating more bleeding. A slightly stained tampon/towel scores 1, a partially stained tampon/towel scores 5, a completely saturated tampon scores 10 and a completely saturated towel scores 20. Small clots/flooding (2cm) score 1. Large clots/flooding (3cm) score 5. Menorrhagia is defined as a PBAC \> 100 during one menstrual period which approximates to a blood loss of \> 80 mL. A PBAC of 400 corresponds to a blood loss of around 300 mL or approximately 80 tampons/towels used. The week 13 PBAC score was calculated using the last 28 days of treatment.
Time frame: Week 13 visit
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A (PGL4001 5mg) | Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13) | 91.5 percentage of patients |
| B (PGL4001 10mg) | Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13) | 92.5 percentage of patients |
| C (Placebo) | Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13) | 18.8 percentage of patients |
p-value: <0.00195% CI: [55.1, 83.2]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [56.2, 84]Cochran-Mantel-Haenszel
Primary
Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit)
Percent change in total fibroid volume from screening to end of treatment visit (Week 13 visit) assessed by MRI and read centrally by a radiologist who was unaware of the study-group assignments. The total fibroid volume was the sum of the individual fibroid volumes.
Time frame: Week 13
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A (PGL4001 5mg) | Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit) | -21.2 percentage of change |
| B (PGL4001 10mg) | Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit) | -12.3 percentage of change |
| C (Placebo) | Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit) | 3 percentage of change |
p-value: 0.00295% CI: [-36.1, -8.2]Wilcoxon (Mann-Whitney)
p-value: 0.00695% CI: [-33, -5.2]Wilcoxon (Mann-Whitney)