Assess the Pharmacokinetics of Rosuvastatin and Simvastatin When Administered Alone or in Combination With Fostamatinib (Statin DDI)

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Fostamatinib; Drug: Rosuvastatin; Drug: Simvastatin

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin; Single, 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	Drug: Fostamatinib; 100-mg tablet; Drug: Rosuvastatin; 20-mg tablet
Experimental: Simvastatin; Single, 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	Drug: Fostamatinib; 100-mg tablet; Drug: Simvastatin; 40-mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 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.

Secondary Outcome Measures

Outcome Measure	Time Frame
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(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.
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.
Frequency of adverse events	Measured throughout the study and 3-5 days after discharge from Period 2, approximately 72 days
Severity of adverse events	Measured throughout the study and 3-5 days after discharge from Period 2, approximately 72 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: November 7, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (Estimate): November 12, 2012

Study Record Updates

• Last Update Posted (Estimate): February 4, 2013
• Last Update Submitted That Met QC Criteria: February 1, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Fostamatinib,; Phase I,; Healthy Subjects,; simvastatin,; rosuvastatin,
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Simvastatin
• Other Study ID Numbers: D4300C00039