Phase I/II clinical study of AKP-022 in healthy Japanese premenopausal female subjects

JRCT ID: jRCT2071230042

Registered date:14/07/2023

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Healthy Japanese premenopausal females
• Date of first enrollment: 17/08/2023
• Target sample size: 48
• Study type: Interventional
• Intervention(s): Two tablets of the study product (1 AKP-022 tablet and 1 Relugolix placebo tablet, or 1 Relugolix tablet and 1 AKP-022 placebo tablet) will be administered orally once daily for 6 weeks. The first dose will be administered between 1 and 5 days after the start of menstruation.

Outcome(s)

Primary Outcome

- Pharmacokinetics (PK) :
Relugolix, NET, E2 and E1 concentrations and PK parameters
- Pharmacodynamics :
Endocrine testing and Bone turnover markers
- Safety

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 45age old
• Gender: Female

Include criteria

- Individuals who are capable of understanding the nature of the study and can provide written voluntary consent to participate in the study.
- Japanese premenopausal females who are aged 18 years or older and 45 years or younger at the time of informed consent.
- Individuals who had a normal menstrual cycle (>= 25 days and <= 38 days) and at least 2 menstrual cycles (>= 3 and <= 7 consecutive days of bleeding) during the 3 months before enrollment.
- Individuals who weigh at least 40 kg with body mass index (BMI) >= 17.6 kg/m2 and < 25.0 kg/m2 at screening.
- Individuals who are in good health when evaluated medically by the investigator or subinvestigator based on the medical history, medical examination, laboratory tests, electrocardiography, etc.
- Individuals who agree to use an appropriate barrier method of contraception at each sexual intercourse from the screening period to the end of the follow-up period or who are not of childbearing potential due to bilateral tubal ligation or hysteroscopic sterilization.

Exclude criteria

- Individuals who are pregnant or lactating, wish to become pregnant between informed consent and the follow-up period, or intend to donate eggs during this period; Individuals with a positive pregnancy test at screening or on the day before the start of treatment.
- Individuals with undiagnosed uterine bleeding.
- Individuals with gynecological abnormality at screening that would interfere with participation in the study; Individuals with positive cervical cytology (other than negative for intraepithelial lesion or malignancy [NILM] according to the Bethesda System).
- Individuals with current or previous osteoporosis, osteopenia, or other metabolic bone disease.
- Individuals with current or previous disease considered inappropriate for participation in the study, such as gynecological diseases, psychiatric/neurological diseases, cerebrovascular/cardiovascular diseases, thrombosis, blood diseases, pulmonary diseases, or endocrine diseases.
- Individuals with current or previous cholelithiasis or cholecystitis.
- Individuals with current or previous malignancy within 5 years before informed consent.
- Individuals with AST, ALT, and/or total bilirubin > 1.5 times the upper limit of normal at screening.
- Individuals with current or previous dyslipidemia or any of the following test results at screening:
a. Fasting LDL cholesterol >= 140 mg/dL
b. Fasting triglycerides >= 150 mg/dL
- Individuals with current or previous diabetes mellitus or the following test result at screening:
a. Fasting plasma glucose >= 126 mg/dL
- Individuals with clinically significant ECG abnormality at screening.
- Individuals whose systolic blood pressure is outside the range of 90 to 140 mmHg, diastolic blood pressure is above 90 mmHg, or heart rate is outside the range of 45 to 100 bpm at screening.
- Individuals with impaired gastrointestinal, hepatic, or renal function that may affect the absorption, metabolism, or excretion of study drugs, or with previous cholecystectomy.
- Individuals who have smoked or used nicotine-containing products within 1 month before screening.
- Individuals with current or previous alcoholism.
- Individuals who test positive for drug abuse at screening.
- Individuals with a positive immunological test result at screening.
- Individuals who have used any of the following medications before screening:
a. Within 3 months: Oral contraceptives, sex hormone drugs, or danazol
b. Within 6 months: Injectable hormonal contraceptives, GnRH analogs, aromatase inhibitors, intrauterine device (IUD), or intrauterine system (IUS) (even if these devices have been removed within 6 months before screening)
- Individuals who are considered by the investigator or subinvestigator to be unsuitable for study treatment based on the medication status (including vitamins, herbs, and supplements) within 2 weeks before the start of study treatment.
- Individuals who have consumed Seville orange or grapefruit (including juice) within 7 days before the start of study treatment.
- Individuals with current or previous hypersensitivity to drug treatments in this study or any of their components or with current or previous severe hypersensitivity to any other drug (including heparin).
- Individuals in whom treatment with E2 or NETA is contraindicated.
a. Individuals with undiagnosed unexpected vaginal bleeding
b. Individuals with current, suspected, or previous breast cancer
c. Individuals with current, suspected, or previous estrogen-dependent malignancy (e.g., endometrial cancer)
d. Individuals with untreated endometrial hyperplasia
e. Individuals with current or previous thrombophlebitis, deep vein thrombosis, or pulmonary embolism
f. Individuals with current or previous arterial thromboembolic disease (e.g., stroke, coronary heart disease)
g. Individuals with protein C, protein S, or antithrombin deficiency or other thrombophilia
h. Individuals with previous hypersensitivity to E2 or NETA
i. Individuals with serious liver disorder
j. Individuals with porphyria
- Individuals from whom at least 200 mL or 400 mL of blood has been collected within 4 or 16 weeks before the start of study treatment, respectively, or who have donated blood components within 2 weeks before the start of study treatment.
- Individuals who have participated in another clinical trial and received an investigational product within 16 weeks before the start of study treatment (within 12 weeks if an approved drug is being studied) or who are currently participating.
- Individuals who, in the opinion of the investigator or subinvestigator, are not eligible for the study.

Related Information

• Primary Sponsor: Hozumi Hiroyasu