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Assess the Pharmacokinetics of Rosuvastatin and Simvastatin When Administered Alone or in Combination With Fostamatinib

Phase 1
Completed
Conditions
Rheumatoid Arthritis
Interventions
Registration Number
NCT01725230
Lead Sponsor
AstraZeneca
Brief Summary

A study to Assess the Pharmacokinetics of Rosuvastatin and Simvastatin when administered alone or in combination with Fostamatinib.

Detailed Description

An Open-label, Non-randomized, 2-Period, Fixed Sequence, Single-center Study to Assess the Pharmacokinetics of Rosuvastatin and Simvastatin in Healthy Subjects when Administered Alone and in Combination with Fostamatinib 100 mg Twice Daily.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
Inclusion Criteria
  • Provision of signed and dated, written informed consent, prior to any study-specific procedures
  • Volunteers will be males or females aged 18 to 55 years and with a weight of at least 50 kg and body mass index (BMI) between 18 and 30 kg/m2, inclusive.
  • Male volunteers should be willing to use barrier contraception, ie, condoms, from the day of first dosing until 2 weeks after the last dosing with IP.
  • Females must have a negative pregnancy test at screening and on admission to the unit, 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 as judged by the Investigator.
  • Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the Investigator.
  • Any clinically significant abnormal findings in vital signs as judged by the Investigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
RosuvastatinFostamatinibSingle, oral dose of rosuvastatin 20mg in first period and in second period (after wash out) fostamatinib 100 mg twice daily, then single oral dose of rosuvastatin 20 mg plus continued oral dosing of fostamatinib 100 mg twice daily, then continue fostamatinib 100 mg twice daily
SimvastatinSimvastatinSingle, oral dose of simvastatin 40 mg in first period and in second period (after wash out) fostamatinib 100 mg twice daily, then single oral dose of simvastatin 40 mg plus continued oral dosing of fostamatinib 100 mg twice daily, then continue fostamatinib 100 mg twice daily
RosuvastatinRosuvastatinSingle, oral dose of rosuvastatin 20mg in first period and in second period (after wash out) fostamatinib 100 mg twice daily, then single oral dose of rosuvastatin 20 mg plus continued oral dosing of fostamatinib 100 mg twice daily, then continue fostamatinib 100 mg twice daily
SimvastatinFostamatinibSingle, oral dose of simvastatin 40 mg in first period and in second period (after wash out) fostamatinib 100 mg twice daily, then single oral dose of simvastatin 40 mg plus continued oral dosing of fostamatinib 100 mg twice daily, then continue fostamatinib 100 mg twice daily
Primary Outcome Measures
NameTimeMethod
Pharmacokinetics of Rosuvastatin measured by AUC and Cmax.Day 1 and Day 6 at predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours postdose.
Pharmacokinetics of Simvastatin measured by AUC and CmaxDay 1 and Day 6 at predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours postdose.
Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics of R406 measured by AUC(0-t), Cmax, Tmax (alone and in combination with rosuvastatin or simvastatin)Day 1 to day 4 at predose, Day 5 and Day 6 at predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours postdose.
Pharmacokinetics of rosuvastatin measured by AUC(0-t), t1/2, Tmax, Cl/F and Vz/F (alone and in combination with fostamatinib)Day 1 and Day 6 at predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours postdose.
Pharmacokinetics of simvastatin measured by AUC, Cmax, AUC(0-t), t1/2, Tmax, C1/F and Vz/F (alone and in combination with fostamatinib)Day 1 and Day 6 at predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours postdose.
Pharmacokinetics of Simvastatin measured by AUC(0-t)m t1/2, and Tmax (alone and in combination with fostamatinib)Day 1 and Day 6 at predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours postdose.
Frequency of adverse eventsMeasured throughout the study and 3-5 days after discharge from Period 2, approximately 72 days
Severity of adverse eventsMeasured throughout the study and 3-5 days after discharge from Period 2, approximately 72 days

Trial Locations

Locations (1)

Research Site

🇺🇸

Overland Park, Kansas, United States

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