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

NCT01682408 | Completed Phase 1

• 1 other identifier: D4300C00019
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Conditions

Pharmacokinetics

Keywords

R406,; Fostamatinib,; Phase I,; Healthy Subjects,; Pharmacokinetics,; Fed/Fasted

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (5)

Part A1

ACTIVE COMPARATOR

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); Drug: Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed

Part A2

ACTIVE COMPARATOR

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); Drug: Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed; Drug: Ranitidine

Part B1

ACTIVE COMPARATOR

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)

Part B2

ACTIVE COMPARATOR

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)

Part B3

ACTIVE COMPARATOR

1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)

Drug: Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)

Interventions

Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference) DRUG

1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)

Part A1; Part A2; Part B3

Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed DRUG

3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed

Part A1; Part A2

Fostamatinib - 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A) DRUG

1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)

Part B1

Fostamatinib - 1 x 150mg mannitol based 38% drug loaded tablet (batch variant B) DRUG

1 x 150mg mannitol based 38% drug loaded tablet(batch variant B)

Part B2

Ranitidine DRUG

150 mg ranitidine

Part A2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Unknown Facility

Overland Park, Kansas, United States

Location

MeSH Terms

Interventions

Ranitidine

Intervention Hierarchy (Ancestors)

Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eleanor Lisbon, MD

  Quintiles Phase I unit 6700 w 115th st Overland Park, Ks 66211

  PRINCIPAL INVESTIGATOR

• Christopher D O'Brien, MD PHD

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 10, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 28, 2012

Record last verified: 2012-12

Locations

US (1)