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Open label study of FSN-011-01 in Japanese women with menopausal disorder with uterus

Open label study of FSN-011-01 in Japanese women with menopausal disorder with uterus

350

Japanese women with a uterus who are suffering from menopausal disorder or ovarian deficiency symptoms and are undergoing or will undergo hormone replacement therapy (HRT) (Aged 40 years or older but younger than 65 years)

Number of subjects treated: 349 (Continuous dosing regimen: 170, Periodic dosing regimen: 179) Number of subjects completed in treatment period: 311 (Continuous dosing regimen: 155, Periodic dosing regimen: 156) Number of subjects discontinued in treatment period: 38 (Continuous dosing regimen: 15, Periodic dosing regimen: 23)

Adverse events occurred in 84.7% (144/170 subjects), 87.7% (157/179 subjects) and 86.2% (301/349 subjects) of the subjects in continuous dosing regimen, periodic dosing regimen and the entire study, respectively. Adverse drug reactions occurred in 49.4% (84/170 subjects), 58.7% (105/179 subjects) and 54.2% (189/349 subjects) of the subjects in continuous dosing regimen, periodic dosing regimen and the entire study, respectively. Serious adverse events occurred in 15 subjects in the entire study (5 and 10 subjects in continuous and periodic dosing regimens, respectively), among which 2 (invasive lobular carcinoma of the breast and intraductal proliferative lesion, both of which occurred in the continuous dosing regimen) were adverse drug reactions. Severe adverse events occurred in 7 subjects in the entire study (3 and 4 subjects in continuous and periodic dosing regimens, respectively), among which 2 (both occurred in the continuous dosing regimen) were adverse drug reactions. Adverse events leading to withdrawal occurred in 12 subjects in the entire study (7 and 5 subjects in continuous and periodic dosing regimens, respectively), among which 7 (5 and 2 subjects in continuous and periodic dosing regimens, respectively) were adverse drug reactions. No adverse events resulting in deaths were observed.

In the FAS, no endometrial hyperplasia was observed. The two-sided 95% confidence interval for its incidence was 0.00 to 1.15%, so it was confirmed that the upper boundary of the 95% confidence interval was below the predetermined level of 2.0%. Similar results were also obtained in the PPS. By dosing regimen, the incidences of endometrial hyperplasia in the FAS were 0.00% (0/156 subjects) and 0.00% (0/162 subjects) for continuous and periodic regimens, respectively. Similar results were also obtained in the PPS.

In the FAS, the changes (mean +- standard deviation) of endometrial thickness at Week 52 or at withdrawal from the baseline values did not substantially differ between the two dosing regimens, being 0.43 (+- 1.363) mm and 0.32 (+- 1.248) mm for the continuous and periodic dosing regimens, respectively. The incidences of endometrial abnormalities at Week 52 or at withdrawal were 0.6% (1/166 subjects) and 2.3% (4/172 subjects) for the continuous and periodic dosing regimens, respectively. Similar tendencies were also observed in the PPS.

After co-administration of FSN-011-01 with estrogen preparation for 52 weeks, no endometrial hypertrophy was observed. It was confirmed that the upper boundary of the two-sided 95% confidence interval for the incidence was below the predetermined level of 2.0%. Regarding safety, the majority of subjects completed the trial, so there were no major tolerability concerns.

No

Fuji Pha, Ltdrma Co

Fuji Pha, Ltdrma Co

+81-3-6862-5566

completed

Mar. 01, 2018

Interventional

Non-randomized multicenter open trial

prevention purpose

3

Japanese menopausal women with uterus to undergo hormone replacement therapy

-Subjects who are positive or indeterminable with 5 mm or more of endometrial thickness in endometrial biopsy
-Subjects who are not able to undergo endometrial biopsy procedurally due to cervical stenosis, etc. at screening (Visit 1).
-Subjects who have serious liver injury at screening (Visit 1)
-Subjects who have or are suspected to have malignant tumor at screening (Visit 1)
-Subjects who have past medical history of breast cancer

Female

Assistance of hormone replacement therapy (HRT) in menopausal non-hysterectomized women

investigational material(s)
Generic name etc : FSN-011-01
INN of investigational material : Progesterone
Therapeutic category code : 247 Estrogen and gestagen preparations
Dosage and Administration for Investigational material : Oral

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
Incidence of endometrial hyperplasia

efficacy
Endometrial thickness

-

Jan. 26, 2018