Assess Pharmacokinetics of Fostamatinib in Fed and Fasted State in Combination With Ranitidine to Assess Bioavailability (PK Combination)

An Open-label, Single-center, 2-Part, Randomized Study to Assess the Pharmacokinetics of R406 in Healthy Subjects When Fostamatinib 150 mg is Administered Alone in Fed and Fasted State and in Combination With Ranitidine in Fasted State, and to Assess the Relative Bioavailability of Process Variants of Tablets

Study to Assess the Pharmacokinetics of R406 in Healthy Subjects when Fostamatinib 150 mg is Administered Alone in Fed and Fasted state and in Combination with Ranitidine in Fasted State, and to Assess the Relative Bioavailability of Process Variants of Tablets

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference); Drug: Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed; Drug: Ranitidine; Drug: Fostamatinib - 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A); Drug: Fostamatinib - 1 x 150mg mannitol based 38% drug loaded tablet (batch variant B)

Detailed Description

An Open-label, Single-center, 2-Part, Randomized Study to Assess the Pharmacokinetics of R406 in Healthy Subjects when Fostamatinib 150 mg is Administered Alone in Fed and Fasted state and in Combination with Ranitidine in Fasted State, and to Assess the Relative Bioavailability of Process Variants of Tablets

• Study Type: Interventional
• Enrollment (Actual): 28
• 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: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study-specific procedures including the genetic sampling and analyses
• Volunteers will be males or females aged 18 to 55 years (inclusive) and with a weight of at least 50 kg and body mass index (BMI) between 18 and 30 kg/m2 inclusive.
• Provision of signed, written, and dated informed consent for optional genetic research. If a volunteer declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the volunteer.
• Male volunteers should be willing to use barrier contraception, ie, condoms from the day of first dosing until 2 weeks after dosing with the IP in Treatment Period 5.
• Females must have a negative pregnancy test at screening and on admission to the CPU (including check-in at each treatment period), must not be lactating and must be of non childbearing potential, confirmed at screening

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
• History or presence of GI, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IP
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the Investigator
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part A1; 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference), fed 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed	Drug: Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference); 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference); Drug: Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed; 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed
Active Comparator: Part A2; 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference) 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed 150 mg ranitidine	Drug: Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference); 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference); Drug: Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed; 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed; Drug: Ranitidine; 150 mg ranitidine
Active Comparator: Part B1; 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)	Drug: Fostamatinib - 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A); 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)
Active Comparator: Part B2; 1 x 150mg mannitol based 38% drug loaded tablet (batch variant B)	Drug: Fostamatinib - 1 x 150mg mannitol based 38% drug loaded tablet (batch variant B); 1 x 150mg mannitol based 38% drug loaded tablet(batch variant B)
Active Comparator: Part B3; 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)	Drug: Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference); 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics profile of R406 in terms of maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC).	Day 1 (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
Pharmacokinetic profile of R406 in terms of area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)], time to Cmax (tmax), terminal half-life (t1/2λz), terminal rate constant (λz).	Day 1 (predose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose
Description of the safety profile in terms of frequency of adverse events.	up to 3 - 5 days after discharge
Description of the safety profile in terms of severity of adverse events.	up to 3 - 5 days after discharge

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Eleanor Lisbon, MD, Quintiles Phase I unit 6700 w 115th st Overland Park, Ks 66211; Study Director: Christopher D O'Brien, MD PHD, AstraZeneca

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: September 6, 2012
• First Submitted That Met QC Criteria: September 6, 2012
• First Posted (Estimate): September 10, 2012

Study Record Updates

• Last Update Posted (Estimate): December 28, 2012
• Last Update Submitted That Met QC Criteria: December 27, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Pharmacokinetics,; R406,; Fostamatinib,; Phase I,; Healthy Subjects,; Fed/Fasted
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Mannitol; Ranitidine; Ranitidine bismuth citrate
• Other Study ID Numbers: D4300C00019