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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01682408

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

9.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics	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: 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) Drug: Ranitidine	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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 Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Overland Park	Kansas	United States

Sponsors and Collaborators

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