Phase I/II study of LF111 (drospirenone) in healthy Japanese women

JRCT ID: jRCT2071200065

Registered date:16/12/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Contraception
• Date of first enrollment: 27/01/2021
• Target sample size: 12
• Study type: Interventional

Intervention(s)

-Single dose period: Single oral dose of LF111-4 mg tablets
-Repeated dose period: LF111-4 mg tablet is orally administered once a day for 24 days at intervals of 7 days or more after a single dose. The starting day of repeated administration should be within the range of the first day to the fifth day of menstruation.

Outcome(s)

Primary Outcome

1) Pharmacokinetics (DRSP plasma concentrations):
-single dose
Cmax,SD, AUC0-tau,SD, AUC0-72,SD, AUC0-inf,SD, Tmax,SD, t1/2,SD, MRT0-72,SD, MRT0-inf,SD, lambda z,SD, CL/FSD, Vd/FSD
-repeated doses
Cmax,SS, AUC0-tau,SS, AUC0-72,SS, AUC0-inf,SS, Tmax,SS, t1/2,SS, MRT0-inf,SS, lambda z,SS, CL/FSS, Vd/FSS, Ctrough, Robs(AUC), Robs(Cmax)
2) Pharmacodynamics (hormone levels): Progesterone, estradiol, LH, FSH
3) Safety: Clinical examination, vital signs, electrocardiography (Standard 12-lead ECG), laboratory tests, gynecological tests, Adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 35age old
• Gender: Female

Include criteria

-Healthy premenopausal Japanese women aged 20 years or older and 35 years or younger at the time of informed consent.
-Non-smokers (those who have not smoked within 6 months before obtaining informed consent).
-Individuals who have a normal menstrual cycle (25 days to 38 days) including the menstrual period (bleeding from 3 days to 7 days) more than once before obtaining informed consent.
-Individuals who agree on appropriate contraceptive methods other than oral contraceptives and intrauterine luteal hormone release system, including partners throughout the study.

Exclude criteria

-Individuals who have a positive pregnancy test at the time of screening.
-Individuals who are pregnant (childbirth, miscarriage or abortion) or breastfed within 3 months before obtaining informed consent.
-A cervical smear (cytology) at screening that was determined to be positive (other than negative (NILM) by Bethesda System 2014).
-Individuals who currently have or have a history of thrombophlebitis, venous or arterial thromboembolic disease (thrombosis, pulmonary embolism, cerebral infarction, myocardial infarction).
-Individuals with severe nervous system disease, digestive system disease, liver disease, or a problem taking the study drug.
-Individuals assessed by the investigator as having clinically significant abnormalities in labolatory test at screening.
-Individuals with renal or adrenal insufficiency or hepatic impairment.
-Individuals with a history of intolerance to oral contraceptives.
-Individuals who are or suspected of alcoholism, drug addiction.
-Individuals who participated in another clinical trial within 16 weeks before administration of the investigational drug and received the investigational drug or who are currently participating in another clinical trial.
-Personnel of the study site or family members of the investigator or subinvestigator.
-Individuals who received 200 mL of blood within 4 weeks before administration of the investigational drug or 400 mL or more of blood within 16 weeks, or Individuals who donated blood components within 2 weeks before administration of the investigational drug.
-Individuals known to be allergic to any of drug.
-Individuals who regularly take the following drugs:
Hormonal preparations (GnRH agonists, GnRH antagonists, estrogens, progestins, estogens/progestins) (all use in the last 6 months excluded)
Agents known to induce hepatic drug-metabolizing enzymes (e.g. Rifampicin, dexamethasone, barbiturates, anticonvulsants, St. John's wort)
Drugs known to inhibit CYP3A4 (e.g. Ketoconazole, verapamil, cimetidine, and macrolides)
Drugs that raise serum potassium (e.g.Aldosterone antagonist,Potassium-sparing diuretics)
-Individuals who consume a lot of xanthine-containing beverages (e.g. Five or more cups of coffee per day)
-Individuals whose temperature at screening falls outside the range of 35-37.5 deg C.
-ECGs at screening that are clinically abnormal.
-Individuals with undiagnosed uterine bleeding.
-Individuals with malignancy or a history of malignancy within 5 years before obtaining informed consent.
-Individuals with a history of the following.
-Individuals undergoing hysterectomy
Gastrointestinal, hepatic, or renal disease that may affect the Pharmacokinetics of the drug
Thromboembolism
Cerebrovascular disorder
Migraine with aura
Adrenal insufficiency
Pancreatitis
Jaundice of pregnancy
Surgery with general anesthesia within 3 months
Pulmonary tuberculosis
-Individuals who the investigator judges be inappropriate.

Related Information

• Primary Sponsor: Kikuyama Ryoko