A Study to Assess the Bioequivalence of R406 in Healthy Volunteers When Given 100mg and 150 mg of Fostamatinib

Study Overview
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Brief Summary
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A study in Healthy Volunteers to Compare the Amount of R406 in Blood When Given Different Formulations of Fostamatinib.

Detailed Description
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An Open-label, Single-center, Randomized, 4-way Crossover Study to Assess the Bioequivalence of R406 in Healthy Volunteers when 100 and 150mg of Fostamatinib are Administered as the 13% Drug-loaded Tablet Versus the 38% Drug-loaded Tablet. Treatment sequences will be determined using two 2-2 crossover designs in sequence, 1 for treatments A and B, and 1 for treatments C and D. The order of the designs containing AB/BA and CD/DC within the overall design, as well as the order of treatments within each design, will be randomized. This gives a total of 8 possible treatment sequences as follows: ABCD, ABDC, BACD, BADC, CDAB, CDBA, DCAB, DCBA.

Official Title
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An Open-label, Single-center, Randomized, 4-way Crossover Study to Assess the Bioequivalence of R406 in Healthy Volunteers When 100 and 150mg of Fostamatinib Are Administered as the 13% Drug-loaded Tablet Versus the 38% Drug-loaded Tablet

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: MCC-based 13% drug loaded tablets
* Drug: Mannitol-based 38% drug-loaded tablet
* Drug: MCC-based 13% drug loaded tablets
* Drug: Mannitol-based 38% drug-loaded tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and nonlactating, non childbearing potential females from 18 to 55 years, inclusive and with a weight of at least 50 kg and BMI between 18 and 30 kg/m2, inclusive Females must have a negative pregnancy test at screening and on admission to the study center of each period, must not be lactating and must be of non childbearing potential Non childbearing potential can be confirmed by being postmenopausal defined as amenorrhea for a least 12 months following cessation of all exogenous hormonal treatments and with FSH and LH levels in the laboratory-defined postmenopausal range Non childbearing potential can be confirmed by documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation. Exclusion Criteria: History of any clinically significant disease or disorder, including GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody Known or suspected history of drug abuse, as judge by the investigator Any clinically significant abnormalities on 12-lead ECG as judged by the Investigator Current smokers, or those who have smoked, used nicotine-containing products, or used smoking cessation treatments within the previous 1 month prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>100mg MCC-based 13% drug-loaded tablets | Drug: MCC-based 13% drug loaded tablets<br>* 50mg tablets, dosed as 2 tablets (100mg total)<br>|
| Experimental: Treatment B<br>100mg mannitol-based 38% drug-loaded tablets | Drug: Mannitol-based 38% drug-loaded tablet<br>* One 100mg tablet<br>|
| Experimental: Treatment C<br>150mg MCC-based 13% drug-loaded tablets | Drug: MCC-based 13% drug loaded tablets<br>* 3 tablets (150mg total)<br>|
| Experimental: Treatment D<br>150mg mannitol-based 38% drug-loaded tablets | Drug: Mannitol-based 38% drug-loaded tablet<br>* One 150 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence of R406 when fostamatinib is administered as two 50mg MCC-based 13% drug-loaded tablets versus one 100mg mannitol-based 38% drug-loaded tablet |  | Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose | 
| Bioequivalence of R406 when fostamatinib is administered as three 50mg MCC-based 13% drug-loaded tablets versus one 150mg mannitol-based 38% drug-loaded tablet |  | Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC for mannitol-based 38% drug-loaded tablets and MCC-based 13% drug-loaded tablets |  | Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose | 
| Cmax for mannitol-based 38% drug-loaded tablets and MCC-based 13% drug-loaded tablets |  | Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdoses | 
| Frequency of adverse events |  | Measured throughout the study and 3 -5 days after discharge from Period 4, approximately 45 days | 
| Severity of adverse events |  | Measured throughout the study and 3 -5 days after discharge from Period 4, approximately 45 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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R406, Fostamatinib, Phase I, Healthy Subjects, Pharmacokinetics, Bioequivalence