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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Mannitol-based 38% drug-loaded tablet; Drug: MCC-based 13% drug loaded tablets

• Registration Number: NCT01645085
• Lead Sponsor: AstraZeneca

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-07-13
• Study First Submitted QC: 2012-07-17
• Study First Posted: 2012-07-20
• Status Verified: 2013-03
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Last Update Submitted: 2013-03-18
• Last Update Posted: 2013-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment D	Mannitol-based 38% drug-loaded tablet	150mg mannitol-based 38% drug-loaded tablets
Treatment A	MCC-based 13% drug loaded tablets	100mg MCC-based 13% drug-loaded tablets
Treatment B	Mannitol-based 38% drug-loaded tablet	100mg mannitol-based 38% drug-loaded tablets
Treatment C	MCC-based 13% drug loaded tablets	150mg MCC-based 13% drug-loaded tablets

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
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