Effects of Administration of Fostamatinib on Blood Concentrations of an Oral Contraceptive in Healthy Female Subjects

AstraZeneca22 enrolled

Overview

A crossover study to assess the effect of repeated doses of fostamatinib on the levels of oral contraceptive (Microgynon® 30) in the blood of healthy female subjects. The study will consist of a screening period of up to 35 days, followed by 2 treatment periods (28 days each) of an oral contraceptive (Microgynon® 30) in the absence and presence of fostamatinib. The study will also evaluate the safety and tolerability of fostamatinib in combination with an oral contraceptive

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Scientific Terminology Rheumatoid Arthritis, Healthy Female Volunteers, Pharmacokinetics, Oral Contraceptive, Drug-drug Interaction Laymen Terminology Level of Oral Contraceptive in Blood, Oral Contraceptive, Rheumatoid Arthritis, Drug -Drug Interaction

Interventions

fostamatinibDRUG

Oral tablets, repeated doses for 21 days (2 x 50mg BID)

Microgynon® 30 (Oral contraceptive)DRUG

Oral tablets, repeated doses

PlaceboDRUG

Oral tablets BID, repeated doses for 21 days

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Female subjects of age 18 to 45 years, inclusive, who are healthy, non-pregnant, not planning pregnancy within the study period * Willing to use a highly effective method of birth control, ie, double barrier method contraception (condom and diaphragm with spermicide) from the first day of Period 1 until 28 days after the last dose * Body weight of at least 50 kg and body mass index (BMI) between 18 and 30 kg/m2 inclusive * Two negative pregnancy tests at least 7 days apart Exclusion Criteria: * History of any clinically significant disease or disorder * History or presence of Gastrointestinal, hepatic, or renal disease * Any condition listed as a contraindication in the Microgynon® 30 labelling * Absolute neutrophil count less than 2.5 x 109/L.

Outcomes

Primary Outcomes

To assess the effects of repeated doses of Fostamatinib on the pharmacokinetics of Microgynon ®30 by assessment of Cssmax and AUCss of ethinyl estradiol (EE), levonorgestrel on Day 21

Time frame: From predose until Day 22 of each Treatment period

Secondary Outcomes

To characterise the PD of progesterone, LH, FSH, and SHBG, following dosing with monophasic oral contraceptive (Microgynon® 30) alone and following coadministration with fostamatinib

PD = pharmacodynamics, LH = luteinising hormone, FSH = follicle stimulating, SHBG = Sex hormone binding globulin

Time frame: From predose until Day 22 of each Treatment period

To determine R-406 plasma concentration-time profile and resulting PK parameters including AUCss, Cssmax, and tmaxss

Time frame: From pre-dose until 12 hours following final dose on Day 21

To determine the safety and tolerability of fostamatinib in combination with an oral contraceptive (Microgynon ®30): adverse event monitoring, vital signs, physical examinations, clinical laboratory tests, ECGs

Time frame: Screening, treatment periods 1 and 2, Follow up