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A Phase III clinical study to evaluate the efficacy and safety of LF111 4 mg in Japanese women desiring contraception

A Phase III clinical study of LF111 in Japanese women desiring contraception

276

Among the 276 subjects in the FAS, the age of subjects (mean +- SD; the same applies hereinafter) was 31.2 +- 6.7 years, 187 subjects (67.75%) were 35 years of age or younger, and 89 subjects (32.25%) were over 35 years of age.

A total of 276 subjects received the investigational product; 241 subjects completed the 13-cycle treatment, and 185 subjects completed the follow-up period of the 13-cycle treatment, excluding 52 subjects who entered extension period and 4 subjects who discontinued the follow-up period of the 13- cycle treatment. No deaths occurred.

A total of 273 subjects (98.9%) experienced TEAEs across 13 cycles, of which 264 subjects (95.7%) experienced adverse drug reactions. A total of mild TEAEs were reported in 116 subjects (42.0%), moderate TEAEs were reported in 157 subjects (56.9%), and no severe TEAEs were reported. A total of significant TEAEs were reported in 6 subjects (2.2%), and 5 TEAEs led to discontinuation in 5 subjects (1.8%). A low incidence of serious TEAEs was observed in 4 subjects (1.5%), and adverse drug reaction was reported in 1 subject (0.4%). Among serious TEAEs, event was reported in 1 subject (0.4%) as a significant TEAE or TEAE leading to discontinuation. Other than adverse events, no notable abnormalities were observed in laboratory tests, tests for sexually transmitted diseases, physical findings, vital signs, gynecological examinations, and standard 12-lead ECG.

The total number of exposure cycles in the FAS was 3319 treatment cycles. One subject became pregnant during these treatment cycles, the pregnancy ratio was 0.36%, the overall Pearl Index was 0.39 (95% confidence interval: 0.01 to 2.18), and the upper limit of the two-sided 95% confidence interval for the overall Pearl Index, which is the evaluation criterion of the primary endpoint, was less than 4, by which efficacy was verified. In subject of pregnancy, the principal investigator determined that the estimated date of conception was within the treatment-free period. A total of 3001 treatment cycles were evaluable in the FAS, with 1 pregnancy occurring during these cycles, resulting in a pregnancy ratio of 0.36% and a Pearl Index of 0.43 (95% confidence interval: 0.01 to 2.41). A total of 2989 perfect cycles were observed in the FAS, and there were no pregnancies during these cycles, with a pregnancy ratio of 0.00% and a Pearl Index of 0.00 (95% confidence interval: - to 1.60). The Kaplan-Meier estimate of the cumulative pregnancy ratio up to 13 cycles was 0.40% (95% confidence interval: 0.06% to 2.81%).

One subject became pregnant during treatment cycles, the pregnancy ratio was 0.36%, the overall Pearl Index was 0.39 (95% confidence interval: 0.01 to 2.18), and the upper limit of the two-sided 95% confidence interval for the overall Pearl Index, which is the evaluation criterion of the primary endpoint, was less than 4, by which efficacy was verified. All TEAEs were mild or moderate, and none were severe. There were no problems of safety, and the tolerability was also good.

https://obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.16340

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210556

Kikuyama Ryoko

ASKA Pharmaceutical Co., Ltd.

2-5-1, Shibaura, Minato-ku, Tokyo, Japan

aska-clinical@aska-pharma.co.jp

Kikuyama Ryoko

ASKA Pharmaceutical Co., Ltd.

2-5-1, Shibaura, Minato-ku, Tokyo, Japan

+81-3-5484-8333

aska-clinical@aska-pharma.co.jp

Complete

Feb. 01, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

other

-Premenopausal Japanese women of childbearing potential aged >=20 years at the time of informed consent
-Desire to use oral contraception continuously for 13 cycles
-Meet one of the following:
a. If the subject is not using a combined oral contraceptive (COC), intrauterine device (IUD), or intrauterine system (IUS) at the time of informed consent, she must be confirmed to have had at least 4 normal menstrual cycles with normal duration of menstruation during 6 months before informed consent.
b. If the subject is using a COC, IUD, or IUS at the time of informed consent, she must be confirmed to have had normal menstrual cycles with normal duration of menstruation before starting the use of COC, IUD, or IUS.
c. If the subject had delivery, abortion, or stillbirth within the past 6 months before informed consent, she must be confirmed to have had at least one normal menstrual cycle with normal duration of menstruation after the delivery, abortion, or stillbirth.

-Pregnant women or women desiring to become pregnant during the study period
-Having a history or current condition of the following:
a. Ovulation disorder such as polycystic ovary syndrome
b. Infertility
c. Unexplained abnormal uterine bleeding
d. Active venous thromboembolism
e. History of severe liver disease or unresolved laboratory abnormalities
f. Severe or acute renal failure
g. Malignant tumor within 5 years before informed consent
h. Lactose intolerance
i. Allergy to any ingredients of the investigational product
j. Alcohol dependence or drug dependence within 6 months before informed consent
k. Disease being treated (or under consideration of treatment) that precludes participation in this study in the opinion of the investigator
-Having screening test results meeting any of the following:
a. Pregnancy confirmed by a positive pregnancy test
b. Resting systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg
c. AST or ALT level >3 times the upper limit of normal (ULN)
d. Obvious abnormalities in laboratory tests (except for those judged to be physiological variations and placed under follow-up)
e. Positive cervical cytology result
f. Abnormalities on transvaginal ultrasonography or breast examination precluding study participation
g. Positive test result for sexually transmitted disease

Female

Contraception

One LF111-4mg tablet will be taken (oral administration) daily for the first 24 days, followed by one LF111-placebo tablet daily for the next 4 days. Administration period will have 13 consecutive cycles, with one cycle defined as 28 days. Extended period will be continued up to Cycle 24.

Overall Pearl Index

+81-3-5213-0028

Jan. 07, 2022

+81-3-6868-7022

Jan. 07, 2022

+81-3-5543-0196

Jan. 07, 2022

none