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

A Single-blind, Placebo-controlled, 2-period, Fixed Sequence Study to Determine the Effects of Coadministration of Fostamatinib 100 mg Twice Daily on the Pharmacokinetics of an Oral Contraceptive in Healthy Female Subjects

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 Overview

• Status: Completed
• 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
• Intervention / Treatment: Drug: Microgynon® 30 (Oral contraceptive); Drug: Placebo; Drug: fostamatinib

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Treatment A; Monophasic oral contraceptive (Microgynon® 30) with placebo tablets	Drug: Microgynon® 30 (Oral contraceptive); Oral tablets, repeated doses; Drug: Placebo; Oral tablets BID, repeated doses for 21 days
EXPERIMENTAL: Treatment B; Monophasic oral contraceptive (Microgynon® 30) and fostamatinib	Drug: Microgynon® 30 (Oral contraceptive); Oral tablets, repeated doses; Drug: fostamatinib; Oral tablets, repeated doses for 21 days (2 x 50mg BID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	From predose until Day 22 of each Treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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		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		Screening, treatment periods 1 and 2, Follow up

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): November 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: January 12, 2011
• First Submitted That Met QC Criteria: January 12, 2011
• First Posted (ESTIMATE): January 13, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 20, 2012
• Last Update Submitted That Met QC Criteria: February 17, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Phase 1, healthy female volunteers, oral contraceptive, pharmacokinetics, Rheumatoid arthritis, RA, fostamatinib
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Contraceptives, Postcoital, Hormonal; Contraceptive Agents; Contraceptives, Oral; Ethinyl estradiol, levonorgestrel drug combination; Ethinyl Estradiol-Norgestrel Combination
• Other Study ID Numbers: D4300C00012