Trial Outcomes & Findings for A Phase 3 Study to Evaluate the Efficacy and Safety of Relugolix (TAK-385) 40 mg Compared With Leuprorelin in the Treatment of Uterine Fibroids (NCT NCT02655237)
NCT ID: NCT02655237
Last Updated: 2019-03-22
Results Overview
PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of \<1 cm/=1 cm/\>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to \>500.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
281 participants
Primary outcome timeframe
Week 6 to 12
Results posted on
2019-03-22
Participant Flow
Participants took part in the study at 34 investigative sites in Japan from 05 March 2016 to 25 September 2017.
Participants with a diagnosis of uterine fibroids were enrolled in 1 of 2 (Relugolix once daily and Leuprorelin once in 4 weeks) treatment groups.
Participant milestones
| Measure |
Relugolix 40 mg
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Overall Study
STARTED
|
139
|
142
|
|
Overall Study
COMPLETED
|
122
|
131
|
|
Overall Study
NOT COMPLETED
|
17
|
11
|
Reasons for withdrawal
| Measure |
Relugolix 40 mg
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Overall Study
Adverse Event
|
10
|
7
|
|
Overall Study
Protocol Deviation
|
2
|
0
|
|
Overall Study
Withdrawal by Participant
|
1
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Recovery Leading to Surgery
|
2
|
1
|
|
Overall Study
Reduction of Hemoglobin Concentration
|
1
|
0
|
|
Overall Study
Randomized but Not Treated
|
1
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Relugolix 40 mg
n=139 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
Total
n=281 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.2 years
STANDARD_DEVIATION 4.98 • n=139 Participants
|
42.6 years
STANDARD_DEVIATION 5.27 • n=142 Participants
|
42.9 years
STANDARD_DEVIATION 5.13 • n=281 Participants
|
|
Sex: Female, Male
Female
|
139 Participants
n=139 Participants
|
142 Participants
n=142 Participants
|
281 Participants
n=281 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=139 Participants
|
0 Participants
n=142 Participants
|
0 Participants
n=281 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Japan
|
139 Participants
n=139 Participants
|
142 Participants
n=142 Participants
|
281 Participants
n=281 Participants
|
|
Height
|
159.8 centimeter (cm)
STANDARD_DEVIATION 5.29 • n=139 Participants
|
159.4 centimeter (cm)
STANDARD_DEVIATION 5.23 • n=142 Participants
|
159.6 centimeter (cm)
STANDARD_DEVIATION 5.25 • n=281 Participants
|
|
Weight
|
58.16 kilogram (kg)
STANDARD_DEVIATION 9.167 • n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
59.53 kilogram (kg)
STANDARD_DEVIATION 9.907 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
58.85 kilogram (kg)
STANDARD_DEVIATION 9.557 • n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Body Mass Index (BMI)
|
22.78 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.506 • n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
23.43 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.657 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
23.11 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.592 • n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Smoking Classification
Never Smoked
|
96 Participants
n=139 Participants
|
89 Participants
n=142 Participants
|
185 Participants
n=281 Participants
|
|
Smoking Classification
Current Smoker
|
19 Participants
n=139 Participants
|
26 Participants
n=142 Participants
|
45 Participants
n=281 Participants
|
|
Smoking Classification
Ex-Smoker
|
24 Participants
n=139 Participants
|
27 Participants
n=142 Participants
|
51 Participants
n=281 Participants
|
|
Birth Experience
Had Birth Experience
|
74 Participants
n=139 Participants
|
75 Participants
n=142 Participants
|
149 Participants
n=281 Participants
|
|
Birth Experience
Had No Birth Experience
|
65 Participants
n=139 Participants
|
67 Participants
n=142 Participants
|
132 Participants
n=281 Participants
|
|
Type of Uterine Fibroid
Subserosal Fibroid
|
54 Participants
n=139 Participants
|
53 Participants
n=142 Participants
|
107 Participants
n=281 Participants
|
|
Type of Uterine Fibroid
Intramural Fibroid
|
117 Participants
n=139 Participants
|
112 Participants
n=142 Participants
|
229 Participants
n=281 Participants
|
|
Type of Uterine Fibroid
Submucosal Fibroid
|
13 Participants
n=139 Participants
|
20 Participants
n=142 Participants
|
33 Participants
n=281 Participants
|
|
Stopped Any Medications for Uterine Fibroids
Had Stopped Any Medications
|
30 Participants
n=139 Participants
|
37 Participants
n=142 Participants
|
67 Participants
n=281 Participants
|
|
Stopped Any Medications for Uterine Fibroids
Had Not Stopped Any Medications
|
109 Participants
n=139 Participants
|
105 Participants
n=142 Participants
|
214 Participants
n=281 Participants
|
|
Any Surgery for Uterine Fibroids
Had Any Surgery for Uterine Fibroids
|
18 Participants
n=139 Participants
|
11 Participants
n=142 Participants
|
29 Participants
n=281 Participants
|
|
Any Surgery for Uterine Fibroids
Had Not Any Surgery for Uterine Fibroids
|
121 Participants
n=139 Participants
|
131 Participants
n=142 Participants
|
252 Participants
n=281 Participants
|
|
Volume of Myoma
|
117.41 cm^3
STANDARD_DEVIATION 126.533 • n=137 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
122.25 cm^3
STANDARD_DEVIATION 124.270 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
119.87 cm^3
STANDARD_DEVIATION 125.184 • n=279 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Volume of Uterus
|
406.25 cm^3
STANDARD_DEVIATION 392.354 • n=136 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
379.07 cm^3
STANDARD_DEVIATION 331.568 • n=139 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
392.51 cm^3
STANDARD_DEVIATION 362.495 • n=275 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Pictorial Blood Loss Assessment Chart (PBAC) Score
|
254.3 score on a scale
STANDARD_DEVIATION 155.28 • n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
263.7 score on a scale
STANDARD_DEVIATION 171.33 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
259.1 score on a scale
STANDARD_DEVIATION 163.39 • n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Numerical Rating Scale (NRS) Score
|
0.63 score on a scale
STANDARD_DEVIATION 0.790 • n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
0.56 score on a scale
STANDARD_DEVIATION 0.559 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
0.59 score on a scale
STANDARD_DEVIATION 0.682 • n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Uterine Fibroid Symptom and Quality of Life (UFS-QOL) Score: Symptom Severity
|
28.4 score on scale
STANDARD_DEVIATION 14.38 • n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
29.7 score on scale
STANDARD_DEVIATION 15.18 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
29.1 score on scale
STANDARD_DEVIATION 14.78 • n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
UFS-QOL Score: Health Related Quality of Life (HRQL) Total
|
80.2 score on a scale
STANDARD_DEVIATION 16.73 • n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
76.8 score on a scale
STANDARD_DEVIATION 19.57 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
78.5 score on a scale
STANDARD_DEVIATION 18.27 • n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Hemoglobin
|
11.49 Gram per deciliter (g/dL)
STANDARD_DEVIATION 1.368 • n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
11.62 Gram per deciliter (g/dL)
STANDARD_DEVIATION 1.377 • n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
11.56 Gram per deciliter (g/dL)
STANDARD_DEVIATION 1.372 • n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Dosage of Leuprorelin Vial
1.88 mg
|
121 Participants
n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
124 Participants
n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
245 Participants
n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
|
Dosage of Leuprorelin Vial
3.75 mg
|
17 Participants
n=138 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
18 Participants
n=142 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
35 Participants
n=280 Participants • Here, number analyzed indicates participants who were evaluated for this baseline characteristic.
|
PRIMARY outcome
Timeframe: Week 6 to 12Population: Full analysis set (FAS) included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of \<1 cm/=1 cm/\>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to \>500.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Percentage of Participants With Total PBAC Score of <10 From Week 6 to 12
|
82.2 percentage of participants
Interval 75.773 to 88.672
|
83.1 percentage of participants
Interval 76.935 to 89.263
|
SECONDARY outcome
Timeframe: Week 2 to 6Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of \<1 cm/=1 cm/\>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to \>500.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Percentage of Participants With Total PBAC Score of <10 From Week 2 to 6
|
64.2 percentage of participants
|
31.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 18 to 24Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of \<1 cm/=1 cm/\>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to \>500.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Percentage of Participants With Total PBAC Score of <10 From Week 18 to 24
|
84.1 percentage of participants
|
94.7 percentage of participants
|
SECONDARY outcome
Timeframe: For 6 weeks before the final dose of study drug (up to Week 24)Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
PBAC score was used to measure volume of menstrual blood loss. Participants used sanitary products designated by sponsor and recorded the numbers of tampons or towels used, clots and flooding in patient diary. Three diagrams used which represented a lightly, moderately stained or completely saturated pad/tampon. Following scores assigned: 1) 1, 5, or 20 points for each pad; 2) 1, 5, or 10 points for each tampon; 3) 1 or 5 points for each blood clot of \<1 cm/=1 cm/\>1 in longest diameter; 4) 5 points for each episode of flooding. The total PBAC score (sum of points) ranges from 0 to \>500.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Percentage of Participants With Total PBAC Score of <10 for 6 Weeks Before the Final Dose of Study Drug
|
79.0 percentage of participants
|
92.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 2, 4, 8, 12 and 24Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
A transvaginal ultrasound was performed to determine myoma volumes. Only the largest myoma among those measurable at visit 1 was measured throughout the study. On the assumption that the myoma was spheroids, the myoma volumes were calculated using 3 diameters (D1, D2, and D3). D1: the longest diameter of the myoma; D2: the longest diameter of the myoma which was perpendicular to D1; D3: the diameter of the myoma which crossed the intersection of D1 and D2 (intersection "Z") and was perpendicular to D1/D2 plane. The formula used for calculation is Myoma volume= D1\*D2\*D3\*π/6.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Percent Change From Baseline in Myoma Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 2
|
-18.74 cm^3
Standard Deviation 31.849
|
-6.68 cm^3
Standard Deviation 33.377
|
|
Percent Change From Baseline in Myoma Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 4
|
-24.99 cm^3
Standard Deviation 46.374
|
-22.44 cm^3
Standard Deviation 31.935
|
|
Percent Change From Baseline in Myoma Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 8
|
-35.92 cm^3
Standard Deviation 39.546
|
-40.62 cm^3
Standard Deviation 25.036
|
|
Percent Change From Baseline in Myoma Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 12
|
-43.28 cm^3
Standard Deviation 33.849
|
-46.87 cm^3
Standard Deviation 24.067
|
|
Percent Change From Baseline in Myoma Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 24
|
-49.75 cm^3
Standard Deviation 34.331
|
-53.71 cm^3
Standard Deviation 24.257
|
SECONDARY outcome
Timeframe: Baseline, Weeks 2, 4, 8, 12 and 24Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
A transvaginal ultrasound was performed for determination of uterine volumes. On the assumption that the uterus was spheroids, the uterine volumes were calculated using 3 diameters (D1, D2, and D3) measured as shown below: D1: the longest diameter of the uterus (unit of length: cm); D2: the longest diameter of the uterus which was perpendicular to D1 (unit of length: cm); D3: the diameter of the uterus which crossed the intersection of D1 and D2 (intersection "Z") and was perpendicular to D1/D2 plane (unit of length: cm). The formula used for calculation is Uterine volume=D1\*D2\*D3\*π/6.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Percent Change From Baseline in Uterine Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 2
|
-22.05 cm^3
Standard Deviation 17.870
|
-6.90 cm^3
Standard Deviation 27.984
|
|
Percent Change From Baseline in Uterine Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 4
|
-28.07 cm^3
Standard Deviation 23.965
|
-17.80 cm^3
Standard Deviation 34.058
|
|
Percent Change From Baseline in Uterine Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 8
|
-34.73 cm^3
Standard Deviation 22.507
|
-33.83 cm^3
Standard Deviation 27.882
|
|
Percent Change From Baseline in Uterine Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 12
|
-39.79 cm^3
Standard Deviation 24.454
|
-38.85 cm^3
Standard Deviation 25.157
|
|
Percent Change From Baseline in Uterine Volumes at Weeks 2, 4, 8, 12 and 24
Change at Week 24
|
-44.87 cm^3
Standard Deviation 29.214
|
-45.73 cm^3
Standard Deviation 27.778
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow up (up to Week 28)Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
Anemia-related measurements consisted of hemoglobin, which were determined at the central laboratory.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up
Change at Week 4
|
0.79 g/dL
Standard Deviation 0.763
|
0.60 g/dL
Standard Deviation 0.789
|
|
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up
Change at Week 8
|
1.20 g/dL
Standard Deviation 1.043
|
1.10 g/dL
Standard Deviation 0.925
|
|
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up
Change at Week 12
|
1.38 g/dL
Standard Deviation 1.134
|
1.31 g/dL
Standard Deviation 1.000
|
|
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up
Change at Week 16
|
1.40 g/dL
Standard Deviation 1.190
|
1.42 g/dL
Standard Deviation 0.978
|
|
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up
Change at Week 20
|
1.47 g/dL
Standard Deviation 1.264
|
1.58 g/dL
Standard Deviation 1.033
|
|
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up
Change at Week 24
|
1.56 g/dL
Standard Deviation 1.281
|
1.65 g/dL
Standard Deviation 1.116
|
|
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, 16, 20, 24 and Follow up
Change at Follow-Up (up to Week 28)
|
1.25 g/dL
Standard Deviation 1.301
|
1.75 g/dL
Standard Deviation 1.182
|
SECONDARY outcome
Timeframe: From Week 6 to 12, from Week 2 to 6, from Week 18 to 24, and for 6 weeks before the final dose (up to Week 24)Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
Pain symptoms were evaluated using the NRS score. NRS score is a self-reported instrument assessing pain from 0 to 10. Higher scores reflect greater level of pain.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Numerical Rating Scale (NRS) Score
Week 6 to 12
|
0.21 score on a scale
Standard Deviation 0.500
|
0.14 score on a scale
Standard Deviation 0.363
|
|
Numerical Rating Scale (NRS) Score
Week 2 to 6
|
0.32 score on a scale
Standard Deviation 0.707
|
0.27 score on a scale
Standard Deviation 0.489
|
|
Numerical Rating Scale (NRS) Score
Week 18 to 24
|
0.12 score on a scale
Standard Deviation 0.308
|
0.11 score on a scale
Standard Deviation 0.289
|
|
Numerical Rating Scale (NRS) Score
For 6 weeks before the final dose (up to Week 24)
|
0.14 score on a scale
Standard Deviation 0.359
|
0.12 score on a scale
Standard Deviation 0.327
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow-up (up to Week 28)Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
UFS-QOL was a 37-item self-reporting tool for evaluating QOL in participants with uterine fibroid. It includes eight symptom-related questions and 29 HRQL questions across six subscales (concern, activities, energy/mood, control, self-consciousness, sexual function). The total symptom severity score is ranging from 0 to 100. The higher scores indicate greater severity.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 4
|
-5.5 score on a scale
Standard Deviation 14.11
|
-4.5 score on a scale
Standard Deviation 16.09
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 8
|
-19.5 score on a scale
Standard Deviation 14.47
|
-17.2 score on a scale
Standard Deviation 16.91
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 12
|
-21.0 score on a scale
Standard Deviation 14.93
|
-23.0 score on a scale
Standard Deviation 14.66
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 16
|
-21.4 score on a scale
Standard Deviation 14.76
|
-24.4 score on a scale
Standard Deviation 14.04
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 20
|
-21.9 score on a scale
Standard Deviation 14.97
|
-24.3 score on a scale
Standard Deviation 14.87
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 24
|
-22.5 score on a scale
Standard Deviation 15.17
|
-25.3 score on a scale
Standard Deviation 14.52
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- Symptom Severity Score at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Follow-Up (up to Week 28)
|
-20.6 score on a scale
Standard Deviation 16.83
|
-25.4 score on a scale
Standard Deviation 14.04
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24 and Follow-up (up to Week 28)Population: FAS included all participants who were randomized and received at least 1 dose of the study drug for the treatment period. The number analyzed is the number of participants with data available for analysis at the given time-point.
UFS-QOL was a 37-item self-reporting tool for evaluating QOL in participants with uterine fibroid. It includes eight symptom-related questions and 29 HRQL questions across six subscales (concern, activities, energy/mood, control, self-consciousness, sexual function). The total HRQL score is ranging from 0 to 100. The higher scores indicate better QOL.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 4
|
2.4 score on a scale
Standard Deviation 12.42
|
3.5 score on a scale
Standard Deviation 12.89
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 8
|
8.1 score on a scale
Standard Deviation 14.48
|
9.5 score on a scale
Standard Deviation 16.78
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 12
|
10.4 score on a scale
Standard Deviation 15.01
|
13.3 score on a scale
Standard Deviation 17.99
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 16
|
10.9 score on a scale
Standard Deviation 14.43
|
14.3 score on a scale
Standard Deviation 18.31
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 20
|
11.5 score on a scale
Standard Deviation 14.65
|
14.5 score on a scale
Standard Deviation 17.59
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Week 24
|
12.0 score on a scale
Standard Deviation 14.91
|
15.8 score on a scale
Standard Deviation 18.13
|
|
Change From Baseline in Uterine Fibroid Symptom and Quality of Life (UFS-QOL)- HRQL Total Scores at Weeks 4, 8, 12, 16, 20, 24 and Follow-up
Change at Follow-Up (up to Week 28)
|
10.9 score on a scale
Standard Deviation 16.53
|
15.7 score on a scale
Standard Deviation 18.08
|
SECONDARY outcome
Timeframe: Up to Week 28Population: Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE)
|
131 Participants
|
139 Participants
|
SECONDARY outcome
Timeframe: Up to Week 28Population: Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.
Vital signs included sitting blood pressure (after the participant has rested for at least 5 minutes), body temperature (oral or tympanic measurement) (degree Celsius \[°C\]) and pulse (beats per minute \[bpm\]) is reported.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Number of Participants With Markedly Abnormal Values of Vital Signs
Diastolic Blood Pressure Upper (>110 mmHg)
|
2 Participants
|
3 Participants
|
|
Number of Participants With Markedly Abnormal Values of Vital Signs
Systolic Blood Pressure Lower (<85 mmHg)
|
3 Participants
|
2 Participants
|
|
Number of Participants With Markedly Abnormal Values of Vital Signs
Systolic Blood Pressure Upper (>180 mmHg)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Markedly Abnormal Values of Vital Signs
Diastolic Blood Pressure Lower (<50 mmHg)
|
5 Participants
|
5 Participants
|
|
Number of Participants With Markedly Abnormal Values of Vital Signs
Pulse Rate Lower (<50 bpm)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Markedly Abnormal Values of Vital Signs
Body temperature Lower (<35.6 °C)
|
23 Participants
|
23 Participants
|
|
Number of Participants With Markedly Abnormal Values of Vital Signs
Body temperature Upper (>37.7 °C)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 28Population: Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.
Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to weight was reported.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Number of Participants With TEAE Related to Weight
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 28Population: Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.
Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to ECG was reported.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Number of Participants With TEAE Related to Standard 12-Lead ECGs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 28Population: Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.
Number of participants with any markedly abnormal values in laboratory tests collected throughout study is reported. WBC = White blood cells, AST = Aspartate Aminotransferase, ALT = Alanine Aminotransferase, GGT = gamma-glutamyl transferase, ULN = upper limit of normal or upper reference limit.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
WBC Upper (>1.5×ULN×10^3 cells/μL)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
Eosinophils Upper (>2×ULN×10^3 cells/μL)
|
3 Participants
|
4 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
Total cholesterol Upper (>300 mg/dL)
|
6 Participants
|
4 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
Triglycerides Upper (>2.5×ULN mg/dL)
|
4 Participants
|
12 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
Creatine kinase Upper (>5×ULN U/L)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
AST Upper (>3×ULN U/L)
|
2 Participants
|
0 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
ALT Upper (>3×ULN U/L)
|
3 Participants
|
2 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
GGT Upper (>3×ULN U/L)
|
10 Participants
|
6 Participants
|
|
Number of Participants With Markedly Abnormal Values of Laboratory Test
Hemoglobin A1c Upper (>7%)
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Up to Week 28Population: Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.
Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to bone mineral density was reported.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Number of Participants With TEAE (Bone Density Decreased) Related to Bone Mineral Density
|
6 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Up to Week 28Population: Safety analysis set included all participants who received at least 1 dose of the study drug for the treatment period.
Number of participants with TEAEs of which threshold was 5% or above in either treatment group related to biochemical bone metabolism markers was reported.
Outcome measures
| Measure |
Relugolix 40 mg
n=138 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 Participants
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Number of Participants With TEAE Related to Biochemical Bone Metabolism Markers
Bone Resorption Test Abnormal
|
7 Participants
|
7 Participants
|
|
Number of Participants With TEAE Related to Biochemical Bone Metabolism Markers
Resorption Bone Increased
|
7 Participants
|
8 Participants
|
Adverse Events
Relugolix 40 mg
Serious events: 0 serious events
Other events: 123 other events
Deaths: 0 deaths
Leuprorelin 1.88 mg or 3.75 mg
Serious events: 2 serious events
Other events: 134 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Relugolix 40 mg
n=138 participants at risk
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 participants at risk
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
Gastrointestinal disorders
Large intestine polyp
|
0.00%
0/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.70%
1/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.70%
1/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Other adverse events
| Measure |
Relugolix 40 mg
n=138 participants at risk
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by relugolix 40 mg, tablets, orally, once daily and leuprorelin acetate placebo matching injection, SC, once in 4 weeks for 24 weeks in treatment period.
|
Leuprorelin 1.88 mg or 3.75 mg
n=142 participants at risk
Relugolix placebo matching tablets, orally, once daily along with leuprorelin acetate placebo matching injection, subcutaneously (SC), once in 4 weeks for 3 to 6 weeks in run-in period followed by leuprorelin acetate 1.88 mg or 3.75 mg, injection, SC, once in 4 weeks and relugolix placebo matching tablets, orally, once daily for 24 weeks in treatment period.
|
|---|---|---|
|
General disorders
Malaise
|
5.8%
8/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.5%
5/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
28.3%
39/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
32.4%
46/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.1%
7/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.3%
9/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Bone density decreased
|
4.3%
6/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
8/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Bone resorption test abnormal
|
5.1%
7/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
4.9%
7/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.8%
8/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.3%
9/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Resorption bone increased
|
5.1%
7/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
8/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Headache
|
15.2%
21/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
9.9%
14/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Dizziness
|
6.5%
9/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
4.9%
7/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Somnolence
|
5.1%
7/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
4.2%
6/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Reproductive system and breast disorders
Metrorrhagia
|
49.3%
68/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
65.5%
93/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Reproductive system and breast disorders
Menorrhagia
|
24.6%
34/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
15.5%
22/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Reproductive system and breast disorders
Genital haemorrhage
|
5.1%
7/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
4.9%
7/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
9.4%
13/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
10.6%
15/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Vascular disorders
Hot flush
|
42.8%
59/138 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
52.8%
75/142 • Up to Week 28
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER