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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01682408
First received: September 6, 2012
Last updated: December 27, 2012
Last verified: December 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Masking: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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). [ Time Frame: 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 ] [ Designated as safety issue: No ]

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). [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Description of the safety profile in terms of frequency of adverse events. [ Time Frame: up to 3 - 5 days after discharge ] [ Designated as safety issue: Yes ]
  • Description of the safety profile in terms of severity of adverse events. [ Time Frame: up to 3 - 5 days after discharge ] [ Designated as safety issue: Yes ]

Enrollment: 28
Study Start Date: September 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682408

Locations
United States, Kansas
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
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01682408     History of Changes
Other Study ID Numbers: D4300C00019
Study First Received: September 6, 2012
Last Updated: December 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
R406,
Fostamatinib,
Phase I,
Healthy Subjects,
Pharmacokinetics,
Fed/Fasted

Additional relevant MeSH terms:
Mannitol
Ranitidine
Ranitidine bismuth citrate
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Anti-Ulcer Agents
Gastrointestinal Agents
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014