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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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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
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* Drug: fostamatinib
* Drug: Microgynon® 30 (Oral contraceptive)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment A<br>Monophasic oral contraceptive (Microgynon® 30) with placebo tablets | Drug: Microgynon® 30 (Oral contraceptive)<br>* Oral tablets, repeated doses<br>Drug: Placebo<br>* Oral tablets BID, repeated doses for 21 days<br>|
| Experimental: Treatment B<br>Monophasic oral contraceptive (Microgynon® 30) and fostamatinib | Drug: fostamatinib<br>* Oral tablets, repeated doses for 21 days (2 x 50mg BID)<br>Drug: Microgynon® 30 (Oral contraceptive)<br>* Oral tablets, repeated doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, healthy female volunteers, oral contraceptive, pharmacokinetics, Rheumatoid arthritis, RA, fostamatinib