Uterine Fibroids
Conditions
Brief summary
Phase III, multicentre, randomized, double-blind, parallel group, long-term study investigating the efficacy and safety of the 5mg and 10mg doses of PGL4001 for the treatment of uterine myoma.
Detailed description
The target population is composed of pre-menopausal women with symptomatic uterine myoma(s) characterised by heavy bleeding.The main objective of this study is to assess the sustained efficacy and safety of long term on-off treatment with PGL4001 5 or 10mg doses on uterine bleeding, myoma size, pain and quality of life.
Interventions
DRUGPGL4001 5 mg
PGL4001 5 mg daily administration
DRUGPGL4001 10 mg
PGL4001 10mg daily administration
Sponsors
PregLem SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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 a Body Mass Index (BMI) ≥ 18 and ≤ 40. * Have FSH levels ≤ 20 mIU/mL * Have excessive uterine bleeding due to myoma. * Have regular menstrual cycles * Have a myomatous uterus \< 16 weeks with at least one myoma ≥ 3 cm in diameter. * If of childbearing potential the subject must be practicing a non-hormonal method of contraception.
Exclusion criteria
* Has a history of or current uterine, cervical, ovarian or breast cancer. * Has a history of or current endometrium atypical hyperplasia or adenocarcinoma. * Has a known severe coagulation disorder. * Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM). * Has abnormal hepatic function at study entry. * Has a positive pregnancy test, 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 |
|---|---|---|
| Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses | 18 months study duration per subject (4 3-month intermittent treatment courses) | Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. Subjects need to be in amenorrhoea at the end of all four treatment courses, i.e for at least 4x35 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses | After 18 months | Controlled bleeding was defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a treatment course. Subjects need to be in controlled bleeding at the end of all 4 treatment courses i.e. for at least 4x56 days. |
| Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids | After 18 months | For the 3 largest myomas at baseline and the 3 largest myomas at the end of treatment course 4 identified by transvaginal ultrasound, length, height and depth were measured and the volume was estimated by applying the equation for the voulme of an ellipsoid (length x height x depht x π/6). Subjects were exposed to 4 3-month intermittent courses. |
| Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4 | After 18 months | Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. |
| Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL) | 18 months | Quality of Life was measured using a validated uterine fibroid symptom questionnaire. Total score for health related quality of Life (HRQL) range from 0 to 100 with higher scores indicating better Quality of Life. Subjects were exposed to 4 3-month intermittent courses. |
| Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS) | After 18 months | Pain was assessed using a Visual Analogue Scale (VAS) ranging from 0 to 100 with higher score indicating more severe pain. Subjects were exposed to 4 3-month intermittent courses. |
| Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL) | After 18 months | Quality of Life was assessed using a validated questionnaire measuring uterine fibroid symptom severity (UFSQoL) where lower scores indicate fewer symtoms and where a level of 23 has been reported for healthy subject (scale 0-100). Subjects were exposed to 4 3-month intermittent courses. |
Countries
Belgium, Czechia, France, Germany, Hungary, Italy, Latvia, Lithuania, Romania, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ulipristal Acetate (PGL4001) 5mg PGL4001 5 mg: PGL4001 5 mg daily administration | 228 |
| Ulipristal Acetate (PGL4001) 10mg PGL4001 10 mg: PGL4001 10mg daily administration | 223 |
| Total | 451 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 16 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Lack of Efficacy | 2 | 3 |
| Overall Study | Lack of return of menses | 12 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Pregnancy | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | surgery | 0 | 3 |
| Overall Study | Withdrawal by Subject | 27 | 20 |
Baseline characteristics
| Characteristic | Ulipristal Acetate (PGL4001) 5mg | Total | Ulipristal Acetate (PGL4001) 10mg |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 228 Participants | 451 Participants | 223 Participants |
| Age, Continuous | 41.6 years STANDARD_DEVIATION 5.4 | 41.5 years STANDARD_DEVIATION 5.2 | 41.4 years STANDARD_DEVIATION 5.1 |
| Pain Assessment (Visual Analogue Scale) | 39.0 units on a scale | 40.5 units on a scale | 43.0 units on a scale |
| Sex: Female, Male Female | 228 Participants | 451 Participants | 223 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Total volume of the 3 largest myoma | 42.6 cm3 | 43.3 cm3 | 43.6 cm3 |
| Uterine Fibroid Symptom Quality of Life Questionnaire Health related Quality of Life (HRQL) | 56.9 units on a scale | 56.0 units on a scale | 55.2 units on a scale |
| Uterine Fibroid Symptom Quality of Life Questionnaire Symptom Severity (UFSQoL) | 50.0 units on a scale | 50.0 units on a scale | 50.0 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 129 / 230 | 131 / 221 |
| serious Total, serious adverse events | 16 / 230 | 12 / 221 |
Outcome results
Primary
Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses
Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. Subjects need to be in amenorrhoea at the end of all four treatment courses, i.e for at least 4x35 days.
Time frame: 18 months study duration per subject (4 3-month intermittent treatment courses)
Population: Full Analysis Set 1 (subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ulipristal Acetate (PGL4001) 5mg | Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses | 48.7 percentage of subjects |
| Ulipristal Acetate (PGL4001) 10mg | Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses | 60.5 percentage of subjects |
Secondary
Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS)
Pain was assessed using a Visual Analogue Scale (VAS) ranging from 0 to 100 with higher score indicating more severe pain. Subjects were exposed to 4 3-month intermittent courses.
Time frame: After 18 months
Population: FAS1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ulipristal Acetate (PGL4001) 5mg | Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS) | -20.0 percentage of change from baseline |
| Ulipristal Acetate (PGL4001) 10mg | Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS) | -23.0 percentage of change from baseline |
Secondary
Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL)
Quality of Life was measured using a validated uterine fibroid symptom questionnaire. Total score for health related quality of Life (HRQL) range from 0 to 100 with higher scores indicating better Quality of Life. Subjects were exposed to 4 3-month intermittent courses.
Time frame: 18 months
Population: Full Analysis Set 1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ulipristal Acetate (PGL4001) 5mg | Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL) | 20.69 percentage of change from baseline |
| Ulipristal Acetate (PGL4001) 10mg | Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL) | 15.52 percentage of change from baseline |
Secondary
Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL)
Quality of Life was assessed using a validated questionnaire measuring uterine fibroid symptom severity (UFSQoL) where lower scores indicate fewer symtoms and where a level of 23 has been reported for healthy subject (scale 0-100). Subjects were exposed to 4 3-month intermittent courses.
Time frame: After 18 months
Population: Full Analysis Set 1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ulipristal Acetate (PGL4001) 5mg | Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL) | -31.25 percentage of change from baseline |
| Ulipristal Acetate (PGL4001) 10mg | Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL) | -28.13 percentage of change from baseline |
Secondary
Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids
For the 3 largest myomas at baseline and the 3 largest myomas at the end of treatment course 4 identified by transvaginal ultrasound, length, height and depth were measured and the volume was estimated by applying the equation for the voulme of an ellipsoid (length x height x depht x π/6). Subjects were exposed to 4 3-month intermittent courses.
Time frame: After 18 months
Population: Full Analysis Set 1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ulipristal Acetate (PGL4001) 5mg | Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids | -67.0 percentage of change from baseline |
| Ulipristal Acetate (PGL4001) 10mg | Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids | -70.4 percentage of change from baseline |
Secondary
Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4
Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval.
Time frame: After 18 months
Population: Full Analysis Set 1 (all subjects who received study treatment once for treatment course 1) (subjects with missing values were excluded from analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ulipristal Acetate (PGL4001) 5mg | Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4 | 69.6 percentage of participants |
| Ulipristal Acetate (PGL4001) 10mg | Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4 | 74.5 percentage of participants |
Secondary
Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses
Controlled bleeding was defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a treatment course. Subjects need to be in controlled bleeding at the end of all 4 treatment courses i.e. for at least 4x56 days.
Time frame: After 18 months
Population: Full analysis set 1 (all subject who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ulipristal Acetate (PGL4001) 5mg | Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses | 67.1 percentage of participants |
| Ulipristal Acetate (PGL4001) 10mg | Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses | 71.9 percentage of participants |