FindTrial
Sign In

Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain.

A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled, Clinical Study to Assess the Efficacy and Safety of Linzagolix in Subjects With Moderate to Severe Endometriosis-associated Pain.

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03992846
Enrollment
486
Registered
2019-06-20
Start date
2019-06-13
Completion date
2022-04-01
Last updated
2025-04-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Endometriosis

Keywords

Dysmenorrhea, Dyspareunia, Dyschezia, Non-menstrual pelvic pain

Brief summary

The primary objective of this study is to demonstrate the efficacy and safety of linzagolix administered orally once daily for 3 months at a dose of 75 mg alone or of 200 mg in combination with add-back hormone replacement therapy (ABT: estradiol (E2) 1 mg / norethisterone acetate (NETA) 0.5 mg) versus placebo, in the management of moderate to severe endometriosis-associated pain (EAP).

Detailed description

This is a prospective, randomized, double-blind, placebo-controlled study to demonstrate the efficacy and safety of linzagolix administered orally once daily at doses of 75 mg alone and 200 mg in combination with low dose ABT (E2 1 mg/NETA 0.5 mg) versus placebo in the management of moderate to severe EAP in 450 women. Eligible subjects who have completed the 6-month treatment period may enter a separate extension study for 6 additional months of active treatment (no placebo control). Subjects who do not continue in the extension study will enter a 6 month treatment-free follow-up phase.

Interventions

DRUG75 mg linzagolix tablet

For oral administration once daily

DRUG200 mg linzagolix tablet

For oral administration once daily

DRUGAdd-back capsule (E2 1 mg / NETA 0.5 mg)

For oral administration once daily

DRUGPlacebo tablet to match 75 mg linzagolix tablet

For oral administration once daily

DRUGPlacebo tablet to match 200 mg linzagolix tablet

For oral administration once daily

DRUGPlacebo capsule to match Add-back capsule

For oral administration once daily

Sponsors

Kissei Pharmaceutical Co., Ltd.
Lead SponsorINDUSTRY

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 49 Years
Healthy volunteers
No

Inclusion criteria

The subject must have: * Her most recent surgical and - if available - histological diagnosis of pelvic endometriosis up to 10 years before screening. * Moderate to severe endometriosis-associated pain during the screening period. * Regular menstrual cycles. * BMI ≥ 18 kg/m2 at the screening visit. -

Exclusion criteria

The subject will be excluded if she: * Is pregnant or breast feeding or is planning a pregnancy within the duration of the treatment period of the study. * Is less than 6 months postpartum or 3 months postabortion/ miscarriage at the time of entry into the screening period. * Has had a surgical history of any major abdominal surgery within 6 months or any interventional surgery for endometriosis performed within a period of 2 months before screening. * Did not respond to prior treatment with GnRH agonists or GnRH antagonists for endometriosis. * Has a history of, or known, osteoporosis or other metabolic bone disease. * Has chronic pelvic pain that is not caused by endometriosis and requires chronic analgesic or other chronic therapy which would interfere with the assessment of endometriosis-associated pain.

Design outcomes

Primary

MeasureTime frameDescription
Reduction of Dysmenorrhea (DYS) at Month 3 - Proportion of RespondersBaseline to Month 3Percentage of subjects with reduction of 1.1 for DYS in mean pelvic pain score within last 28 days prior to Month 3 or discontinuation, and stable or decreased use of analgesics for Endometriosis-associated pain (=EAP) within the same calendar days.
Reduction of Non-menstrual Pelvic Pain (NMPP) at Month 3 - Proportion of RespondersBaseline to Month 3Percentage of subjects with reduction of 0.8 for NMPP in mean pelvic pain score within last 28 days prior to Month 3 or discontinuation, and stable or decreased use of analgesics for Endometriosis-associated pain (=EAP) within the same calendar days.

Countries

Austria, Bulgaria, Czechia, France, Hungary, Poland, Romania, Spain, Ukraine, United States

Participant flow

Recruitment details

Of the 854 subjects screened, 486 were randomized. Between randomization and Day 1 (i.e., first day of dosing), 2 subjects in the LGX 75 mg group discontinued due to protocol deviation. Thus, 484 randomized subjects were treated and comprised the FAS and SAF.

Pre-assignment details

Participants with a diagnosis of endometriosis were enrolled in a 1:1:1 ratio in one of three treatment groups: Linzagolix (=LGX) 75 mg, LGX 200 mg+Add-back (=ABT) or Placebo.

Participants by arm

ArmCount
LGX 75 mg
One Linzagolix 75 mg tablet, One Linzagolix 200 mg matching placebo tablet and one Add-back matching placebo capsule were administered once daily orally for 6 months.
160
LGX 200 mg+ABT
One Linzagolix 200 mg tablet, One Linzagolix 75 mg matching placebo tablet and one Add-back capsule (E2 1 mg / NETA 0.5 mg) were administered once daily orally for 6 months.
162
Placebo
One Linzagolix 75 mg matching placebo tablet, one Linzagolix 200 mg matching placebo tablet and one Add-back matching placebo capsule were administered once daily orally for 6 months.
162
Total484

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyAdverse Event863
Overall StudyLost to Follow-up011
Overall StudyPregnancy201
Overall StudyProtocol Violation120
Overall StudySponsor decided to exclude the patient100
Overall StudyWithdrawal by Subject81020

Baseline characteristics

CharacteristicTotalPlaceboLGX 75 mgLGX 200 mg+ABT
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
484 Participants162 Participants160 Participants162 Participants
Age, Continuous34.9 Years
STANDARD_DEVIATION 6.6
34.9 Years
STANDARD_DEVIATION 6.8
35.1 Years
STANDARD_DEVIATION 6.4
34.6 Years
STANDARD_DEVIATION 6.8
Age, Customized35.0 Years35.0 Years35.5 Years35.0 Years
BMI24.27 kg/m^2
STANDARD_DEVIATION 4.95
24.14 kg/m^2
STANDARD_DEVIATION 4.44
24.60 kg/m^2
STANDARD_DEVIATION 5.23
24.09 kg/m^2
STANDARD_DEVIATION 5.17
Ethnicity (NIH/OMB)
Hispanic or Latino
13 Participants1 Participants5 Participants7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
471 Participants161 Participants155 Participants155 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Asian
1 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
Black or African American
4 Participants2 Participants1 Participants1 Participants
Race (NIH/OMB)
More than one race
1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
477 Participants160 Participants158 Participants159 Participants
Region of Enrollment
Austria
1 Participants1 Participants0 Participants0 Participants
Region of Enrollment
Bulgaria
13 Participants4 Participants4 Participants5 Participants
Region of Enrollment
Czechia
6 Participants1 Participants2 Participants3 Participants
Region of Enrollment
France
1 Participants0 Participants0 Participants1 Participants
Region of Enrollment
Hungary
2 Participants2 Participants0 Participants0 Participants
Region of Enrollment
Poland
179 Participants57 Participants58 Participants64 Participants
Region of Enrollment
Romania
49 Participants19 Participants18 Participants12 Participants
Region of Enrollment
Spain
4 Participants1 Participants1 Participants2 Participants
Region of Enrollment
Ukraine
203 Participants70 Participants70 Participants63 Participants
Region of Enrollment
United States
26 Participants7 Participants7 Participants12 Participants
Sex: Female, Male
Female
484 Participants162 Participants160 Participants162 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants0 Participants
Weight66.42 kg
STANDARD_DEVIATION 13.77
65.81 kg
STANDARD_DEVIATION 11.96
67.73 kg
STANDARD_DEVIATION 14.45
65.75 kg
STANDARD_DEVIATION 14.75

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 1600 / 1620 / 162
other
Total, other adverse events
83 / 16094 / 16269 / 162
serious
Total, serious adverse events
1 / 1602 / 1620 / 162

Outcome results

Primary

Reduction of Dysmenorrhea (DYS) at Month 3 - Proportion of Responders

Percentage of subjects with reduction of 1.1 for DYS in mean pelvic pain score within last 28 days prior to Month 3 or discontinuation, and stable or decreased use of analgesics for Endometriosis-associated pain (=EAP) within the same calendar days.

Time frame: Baseline to Month 3

ArmMeasureValue (NUMBER)
LGX 75 mgReduction of Dysmenorrhea (DYS) at Month 3 - Proportion of Responders44.0 Percentage of responders
LGX 200 mg+ABTReduction of Dysmenorrhea (DYS) at Month 3 - Proportion of Responders72.9 Percentage of responders
PlaceboReduction of Dysmenorrhea (DYS) at Month 3 - Proportion of Responders23.5 Percentage of responders
p-value: <0.00197.5% CI: [1.46, 4.49]Bonferroni-corrected p-value
p-value: <0.00197.5% CI: [4.86, 15.91]Bonferroni-corrected p-value
Primary

Reduction of Non-menstrual Pelvic Pain (NMPP) at Month 3 - Proportion of Responders

Percentage of subjects with reduction of 0.8 for NMPP in mean pelvic pain score within last 28 days prior to Month 3 or discontinuation, and stable or decreased use of analgesics for Endometriosis-associated pain (=EAP) within the same calendar days.

Time frame: Baseline to Month 3

ArmMeasureValue (NUMBER)
LGX 75 mgReduction of Non-menstrual Pelvic Pain (NMPP) at Month 3 - Proportion of Responders38.9 Percentage of responders
LGX 200 mg+ABTReduction of Non-menstrual Pelvic Pain (NMPP) at Month 3 - Proportion of Responders47.3 Percentage of responders
PlaceboReduction of Non-menstrual Pelvic Pain (NMPP) at Month 3 - Proportion of Responders30.9 Percentage of responders
p-value: 0.27997.5% CI: [0.83, 2.45]Bonferroni-corrected p-value
p-value: 0.00797.5% CI: [1.18, 3.42]Bonferroni-corrected p-value

Source: ClinicalTrials.gov · Data processed: Feb 9, 2026