Endometriosis
Conditions
Keywords
Dysmenorrhea, Dyspareunia, Dyschezia, Non-menstrual pelvic pain
Brief summary
The primary objective of this extension study is to assess the maintenance of efficacy of linzagolix administered orally once daily for up to an additional 6 months (for up to 12 months of treatment in total) in women who have already completed 6 months of linzagolix treatment at a dose of 75 mg alone or of 200 mg in combination with ABT (E2 1 mg / NETA 0.5 mg), in the management of moderate to severe endometriosis-associated pain (EAP) in women with surgically confirmed endometriosis.
Detailed description
This is a prospective, randomized, double-blind study. Subjects who have completed the 6-month Treatment Period in 18-OBE2109-002 - Edelweiss 2 study (herein referred to as main study) will be invited to enter the present extension study. Month 6 visit of the main study is a decision point for Subjects to either end treatment and enter a post-treatment follow up (part of the main study), or to opt for a 6-month treatment extension. All subjects will receive once daily either linzagolix 75 mg alone (with ABT placebo) or 200 mg combined with ABT for 6 months. Subjects who received placebo during the main study will be randomized to either linzagolix 75 mg alone (with ABT placebo) or linzagolix 200 mg with ABT. Subjects who received active treatment during the main study will continue with the same treatment. Double-dummy design will be used in order to maintain the blinding of the study. After end of treatment in the extension study (6-month treatment period: from Month 6 to Month 12), subjects will enter a post-treatment Follow-Up Period of 6 months with no investigational medicinal product (IMP) or - for subjects willing to continue treatment - a second extension study will be proposed.
Interventions
For oral administration once daily
For oral administration once daily
For oral administration once daily
For oral administration once daily
For oral administration once daily
For oral administration once daily
Sponsors
Kissei Pharmaceutical Co., Ltd.
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
The subject must have: * completed the 6-month treatment in the main study * agreed to continue to use only the analgesic rescue medication permitted by the protocol during the Treatment and Follow-up Periods * agreed to continue to comply with the requirements of the study protocol for the duration of the extension study
Exclusion criteria
The subject will be excluded if she: * is pregnant or breast feeding or is planning a pregnancy within the duration of the of the study (including the Follow-up Period) * likely to require treatment during the study with any of the restricted medications * has any other clinically significant gynecologic condition identified during the main study on transvaginal ultrasound (TVUS), on endometrial biopsy or at the manual breast examination, which might interfere with the study efficacy and safety objectives * meets any of the main study discontinuation criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dysmenorrhea | 6 Months | Monthly Severity Data of dysmenorrhea (DYS) at Month 6 were measured on a 4-point (0: No pain, 1: Mild pain, 2: Moderate pain, 3: Severe pain) Verbal Rating Scale (VRS). The Mean±SD of Monthly Severity Data for each treatment arm were calculated and provided as the efficacy data. |
| Non-menstrual Pelvic Pain | 6 Months | Monthly Severity Data of non-menstrual pelvic pain (NMPP) at Month 6 were measured on a 4-point (0: No pain, 1: Mild pain, 2: Moderate pain, 3: Severe pain) Verbal Rating Scale (VRS). The Mean±SD of Monthly Severity Data for each treatment arm were calculated and provided as the efficacy data. |
Countries
Canada, Puerto Rico, United States
Participant flow
Recruitment details
Of the 85 subjects randomized in the Edelweiss 2 study, 37 completed the 6-month treatment. Of the 37 subjects, 30 subjects opted to participate in the current extension study (7 from Placebo, 13 from LGX 75 mg, and 10 from LGX 200 mg+ABT). At entry into the extension study, the 7 subjects in the placebo group were re-randomized to an active LGX group (PBO/LGX 75 mg: 3, PBO/LGX 200 mg+ABT: 4). Subjects receiving LGX during Edelweiss 2 study, continued treatment as randomized in the main study.
Pre-assignment details
Subjects who received placebo in the main study were randomized in a 1:1 ratio to either linzagolix 75 mg alone (with ABT-matching placebo) or linzagolix 200 mg with ABT, as per the main study randomization schedule.
Participants by arm
| Arm | Count |
|---|---|
| LGX 75 mg \[Main study: 6 months\] The IMPs mentioned below were administered once daily orally.
* 1 x Linzagolix 75 mg tab.
* 1 x Linzagolix 200 mg placebo tab.
* 1 x ABT placebo cap.
\[Extension study: 6 months\] Same treatment as the main study | 13 |
| LGX 200 mg+ABT \[Main study: 6 months\] The IMPs mentioned below were administered once daily orally.
* 1 x Linzagolix 200 mg tab.
* 1 x Linzagolix 75 mg placebo tab.
* 1 x ABT cap. (E2 1 mg / NETA 0.5 mg)
\[Extension study: 6 months\] Same treatment as the main study | 10 |
| Placebo/LGX 75 mg \[Main study: 6 months\] The IMPs mentioned below were administered once daily orally.
* 1 x Linzagolix 75 mg placebo tab.
* 1 x Linzagolix 200 mg placebo tab.
* 1 x ABT placebo cap.
\[Extension study: 6months\] Same treatment as LGX 75 mg group in the extension study | 3 |
| Placebo/LGX 200 mg+ABT \[Main study: 6 months\] The IMPs mentioned below were administered once daily orally.
* 1 x Linzagolix 75 mg placebo tab.
* 1 x Linzagolix 200 mg placebo tab.
* 1 x ABT placebo cap
\[Extension study: 6 months\] Same treatment as LGX 200 mg+ABT group in the extension study | 4 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Hysterectomy planned | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
| Overall Study | Study termination | 6 | 5 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LGX 75 mg | LGX 200 mg+ABT | Placebo/LGX 75 mg | Placebo/LGX 200 mg+ABT | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 10 Participants | 3 Participants | 4 Participants | 30 Participants |
| Age, Continuous | 33.6 Years STANDARD_DEVIATION 6 | 30.6 Years STANDARD_DEVIATION 7.7 | 29.0 Years STANDARD_DEVIATION 7.2 | 31.5 Years STANDARD_DEVIATION 7.1 | 31.9 Years STANDARD_DEVIATION 6.7 |
| Age, Customized | 34.0 Years | 30.5 Years | 31.0 Years | 33.5 Years | 32.0 Years |
| BMI | 29.650 kg/m2 STANDARD_DEVIATION 4.27 | 28.390 kg/m2 STANDARD_DEVIATION 9.01 | 28.230 kg/m2 STANDARD_DEVIATION 9.46 | 27.300 kg/m2 STANDARD_DEVIATION 6.86 | 28.770 kg/m2 STANDARD_DEVIATION 6.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 1 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 5 Participants | 2 Participants | 3 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 9 Participants | 3 Participants | 4 Participants | 28 Participants |
| Region of Enrollment Canada | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Puerto Rico | 2 participants | 1 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 11 participants | 8 participants | 3 participants | 4 participants | 26 participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 3 Participants | 4 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 80.992 kg STANDARD_DEVIATION 14.425 | 76.446 kg STANDARD_DEVIATION 22.398 | 72.910 kg STANDARD_DEVIATION 29.701 | 76.143 kg STANDARD_DEVIATION 27.3 | 77.979 kg STANDARD_DEVIATION 18.972 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 10 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 4 / 13 | 4 / 10 | 0 / 3 | 0 / 4 |
| serious Total, serious adverse events | 1 / 13 | 0 / 10 | 0 / 3 | 0 / 4 |
Outcome results
Primary
Dysmenorrhea
Monthly Severity Data of dysmenorrhea (DYS) at Month 6 were measured on a 4-point (0: No pain, 1: Mild pain, 2: Moderate pain, 3: Severe pain) Verbal Rating Scale (VRS). The Mean±SD of Monthly Severity Data for each treatment arm were calculated and provided as the efficacy data.
Time frame: 6 Months
Population: Of the 37 subjects who completed the main study (NCT03986944), 30 subjects participated in the extension study (NCT04372121). Of these 30, there were no subjects who had the Monthly Severity Data of DYS and/or NMPP on Day 1 or Month 12 to evaluate the efficacy but there were 5 subjects that had Monthly Severity Data on Month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LGX 75 mg | Dysmenorrhea | 2.0 score on a scale | Standard Deviation 0 |
| LGX 200 mg+ABT | Dysmenorrhea | 2.0 score on a scale | Standard Deviation 0 |
| Placebo/LGX 75 mg | Dysmenorrhea | 2.5 score on a scale | Standard Deviation 0.5 |
| Placebo/LGX 200 mg+ABT | Dysmenorrhea | 2.0 score on a scale | Standard Deviation 0 |
Primary
Non-menstrual Pelvic Pain
Monthly Severity Data of non-menstrual pelvic pain (NMPP) at Month 6 were measured on a 4-point (0: No pain, 1: Mild pain, 2: Moderate pain, 3: Severe pain) Verbal Rating Scale (VRS). The Mean±SD of Monthly Severity Data for each treatment arm were calculated and provided as the efficacy data.
Time frame: 6 Months
Population: Of the 37 subjects who completed the main study (NCT03986944), 30 subjects participated in the extension study (NCT04372121). Of these 30, there were no subjects who had the Monthly Severity Data of DYS and/or NMPP on Day 1 or Month 12 to evaluate the efficacy but there were 5 subjects that had Monthly Severity Data on Month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LGX 75 mg | Non-menstrual Pelvic Pain | 1.0 score on a scale | Standard Deviation 0 |
| LGX 200 mg+ABT | Non-menstrual Pelvic Pain | 2.0 score on a scale | Standard Deviation 0 |
| Placebo/LGX 75 mg | Non-menstrual Pelvic Pain | 2.5 score on a scale | Standard Deviation 0.5 |
| Placebo/LGX 200 mg+ABT | Non-menstrual Pelvic Pain | 2.0 score on a scale | Standard Deviation 0 |