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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: MCC-based 13% drug loaded tablets; Drug: MCC-based 13% drug loaded tablets; Drug: Mannitol-based 38% drug-loaded tablet; Drug: Mannitol-based 38% drug-loaded tablet

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 Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Chris O'Brien, MEDICAL SCIENCE DIRECTOR, AstraZeneca; Principal Investigator: David Mathews, MD, Quintiles, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: July 13, 2012
• First Submitted That Met QC Criteria: July 17, 2012
• First Posted (Estimate): July 20, 2012

Study Record Updates

• Last Update Posted (Estimate): March 19, 2013
• Last Update Submitted That Met QC Criteria: March 18, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Bioequivalence; Phase I; Healthy Subjects; Fostamatinib; R406
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: D4300C00020