Leiomyoma, Uterine Hemorrhage
Conditions
Brief summary
This study will evaluate the superiority of ulipristal acetate versus placebo for the treatment of abnormal uterine bleeding associated with uterine fibroids
Interventions
UPA tablet
DRUGPlacebo
Matching placebo tablet.
Sponsors
Allergan
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
* Pre-menopausal women, 18-50 years, inclusive. * Cyclic abnormal uterine bleeding (heavy or prolonged). * Menstrual blood loss (MBL) of ≥ 80 mL as measured by the alkaline hematin method in the first 8 days of menses. * Minimum of one discrete leiomyoma observable by transvaginal ultrasound. * Endometrial biopsy without evidence of malignancy or atypical or non-atypical hyperplasia
Exclusion criteria
* History of uterine surgery that would interfere with the study endpoints. * Known coagulation disorder including bleeding disorder or clotting disorder. * History of, or current uterine, cervix, ovarian, or breast cancer. * Alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), or total bilirubin two times or greater than the upper limit of normal rang
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Absence of Bleeding During the Last 35 Consecutive Days on Treatment | Last 35 consecutive days on treatment in the 12-week Treatment Period | Participants recorded bleeding in a daily diary. Absence of bleeding was defined as no bleeding days (i.e. no entries for bleeding or heavy bleeding; however, spotting was allowed), during the last 35 consecutive days on treatment in the 12-week Treatment Period. |
| Time to Absence of Bleeding on Treatment | From first dose up to the end of the 12-week Treatment Period | Time to absence of bleeding was defined as the duration in days from first dose to the first day in the time interval in which absence of bleeding occurs and persists through the last dose on treatment. The persistence of absence of bleeding occurred for a minimum of 35 consecutive days counting backward from the last dose on treatment in the 12-week Treatment Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Absence of Bleeding From Day 11 Through the End of Treatment | Day 11 through the end of the 12-week Treatment Period | Participants recorded bleeding in a daily diary. Absence of bleeding was defined as no bleeding days (i.e. no entries for bleeding or heavy bleeding; however, spotting was allowed), starting from Day 11 through the end of the 12-week Treatment Period. |
| Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period | Baseline (Day 1-4) to the end of 12-week Treatment Period | The UFS-QOL is a uterine fibroid-specific questionnaire consisting of 37 questions developed to evaluate symptoms of uterine fibroids and their impact on health-related quality of life in women with leiomyomas. The first 8 questions comprise the Symptom Severity subscale to assess symptoms experienced by women with uterine leiomyomas, the remaining 29 questions comprise 6 subscales (Concern, Activities, Energy/mood, Control, Self-consciousness, Sexual Function) which overall deal with women's feelings and experiences regarding impact of uterine leiomyoma symptoms on her life. Each item is scored between 1 and 5, where 1=none of the time or not at all and 5=all of the time or a very great deal. A Revised Activities subscale was created to include the most relevant items pertaining to physical and social activities with a total possible score of 0 to 100. Higher Revised Activities subscale scores indicate less impact on activities. A positive change from Baseline indicates improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo tablet (5 mg and 10 mg), orally, once daily for 12 weeks. | 56 |
| UPA 5 mg UPA 5 mg tablet plus matching placebo 10 mg tablet, orally, once daily for 12 weeks. | 53 |
| UPA 10 mg UPA 10 mg tablet plus matching placebo 5 mg tablet, orally, once daily for 12 weeks. | 48 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 3 | 1 |
| Overall Study | Other Miscellaneous Reasons | 1 | 0 | 3 |
| Overall Study | Protocol Violation | 1 | 0 | 3 |
| Overall Study | Withdrawal of Consent | 4 | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | UPA 5 mg | UPA 10 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 5.1 | 40.5 years STANDARD_DEVIATION 5.9 | 41.3 years STANDARD_DEVIATION 5.1 | 41.1 years STANDARD_DEVIATION 5.4 |
| Sex: Female, Male Female | 56 Participants | 53 Participants | 48 Participants | 157 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 | 0 / 56 | 0 / 53 | 0 / 48 |
| other Total, other adverse events | 4 / 56 | 8 / 53 | 12 / 48 |
| serious Total, serious adverse events | 1 / 56 | 1 / 53 | 2 / 48 |
Outcome results
Primary
Percentage of Participants With Absence of Bleeding During the Last 35 Consecutive Days on Treatment
Participants recorded bleeding in a daily diary. Absence of bleeding was defined as no bleeding days (i.e. no entries for bleeding or heavy bleeding; however, spotting was allowed), during the last 35 consecutive days on treatment in the 12-week Treatment Period.
Time frame: Last 35 consecutive days on treatment in the 12-week Treatment Period
Population: Intent-to-Treat (ITT) Population included all randomized participants. Data was summarized as per the treatment assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Absence of Bleeding During the Last 35 Consecutive Days on Treatment | 1.8 percentage of participants |
| UPA 5 mg | Percentage of Participants With Absence of Bleeding During the Last 35 Consecutive Days on Treatment | 47.2 percentage of participants |
| UPA 10 mg | Percentage of Participants With Absence of Bleeding During the Last 35 Consecutive Days on Treatment | 58.3 percentage of participants |
Primary
Time to Absence of Bleeding on Treatment
Time to absence of bleeding was defined as the duration in days from first dose to the first day in the time interval in which absence of bleeding occurs and persists through the last dose on treatment. The persistence of absence of bleeding occurred for a minimum of 35 consecutive days counting backward from the last dose on treatment in the 12-week Treatment Period.
Time frame: From first dose up to the end of the 12-week Treatment Period
Population: ITT Population included all randomized participants. Data was summarized as per the treatment assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Absence of Bleeding on Treatment | NA days |
| UPA 5 mg | Time to Absence of Bleeding on Treatment | NA days |
| UPA 10 mg | Time to Absence of Bleeding on Treatment | 9.5 days |
Secondary
Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period
The UFS-QOL is a uterine fibroid-specific questionnaire consisting of 37 questions developed to evaluate symptoms of uterine fibroids and their impact on health-related quality of life in women with leiomyomas. The first 8 questions comprise the Symptom Severity subscale to assess symptoms experienced by women with uterine leiomyomas, the remaining 29 questions comprise 6 subscales (Concern, Activities, Energy/mood, Control, Self-consciousness, Sexual Function) which overall deal with women's feelings and experiences regarding impact of uterine leiomyoma symptoms on her life. Each item is scored between 1 and 5, where 1=none of the time or not at all and 5=all of the time or a very great deal. A Revised Activities subscale was created to include the most relevant items pertaining to physical and social activities with a total possible score of 0 to 100. Higher Revised Activities subscale scores indicate less impact on activities. A positive change from Baseline indicates improvement.
Time frame: Baseline (Day 1-4) to the end of 12-week Treatment Period
Population: Data was summarized as per treatment assigned and included all participants with data at both Baseline and Week 12. The Baseline row shows the actual scores. The results at Week 12 are the difference in scores from Baseline to Week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period | Change from Baseline at Week 12 | 18.26 score on a scale | Standard Deviation 27.52 |
| Placebo | Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period | Baseline | 34.51 score on a scale | Standard Deviation 26.41 |
| UPA 5 mg | Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period | Change from Baseline at Week 12 | 53.00 score on a scale | Standard Deviation 34.36 |
| UPA 5 mg | Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period | Baseline | 29.60 score on a scale | Standard Deviation 23.34 |
| UPA 10 mg | Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period | Change from Baseline at Week 12 | 61.04 score on a scale | Standard Deviation 31.99 |
| UPA 10 mg | Change From Baseline in Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) Revised Activities Subscale Score at the End of Treatment Period | Baseline | 28.15 score on a scale | Standard Deviation 23.39 |
Secondary
Percentage of Participants With Absence of Bleeding From Day 11 Through the End of Treatment
Participants recorded bleeding in a daily diary. Absence of bleeding was defined as no bleeding days (i.e. no entries for bleeding or heavy bleeding; however, spotting was allowed), starting from Day 11 through the end of the 12-week Treatment Period.
Time frame: Day 11 through the end of the 12-week Treatment Period
Population: ITT Population included all randomized participants. Data was summarized as per the treatment assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Absence of Bleeding From Day 11 Through the End of Treatment | 0.0 percentage of participants |
| UPA 5 mg | Percentage of Participants With Absence of Bleeding From Day 11 Through the End of Treatment | 43.4 percentage of participants |
| UPA 10 mg | Percentage of Participants With Absence of Bleeding From Day 11 Through the End of Treatment | 58.3 percentage of participants |