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

• ClinicalTrials.gov Identifier: NCT01725230
• Recruitment Status: Completed
• First Posted: November 12, 2012
• Last Update Posted: February 4, 2013
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: Fostamatinib; Drug: Rosuvastatin; Drug: Simvastatin	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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 Start Date: November 2012
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: January 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics of Rosuvastatin measured by AUC and Cmax. [ Time Frame: 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. ]
2. Pharmacokinetics of Simvastatin measured by AUC and Cmax [ Time Frame: 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 :

1. Pharmacokinetics of R406 measured by AUC(0-t), Cmax, Tmax (alone and in combination with rosuvastatin or simvastatin) [ Time Frame: 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. ]
2. Pharmacokinetics of rosuvastatin measured by AUC(0-t), t1/2, Tmax, Cl/F and Vz/F (alone and in combination with fostamatinib) [ Time Frame: 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. ]
3. Pharmacokinetics of Simvastatin measured by AUC(0-t)m t1/2, and Tmax (alone and in combination with fostamatinib) [ Time Frame: 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. ]
4. Pharmacokinetics of simvastatin measured by AUC, Cmax, AUC(0-t), t1/2, Tmax, C1/F and Vz/F (alone and in combination with fostamatinib) [ Time Frame: 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. ]
5. Frequency of adverse events [ Time Frame: Measured throughout the study and 3-5 days after discharge from Period 2, approximately 72 days ]
6. Severity of adverse events [ Time Frame: Measured throughout the study and 3-5 days after discharge from Period 2, approximately 72 days ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Kansas

Research Site

Overland Park, Kansas, United States

Sponsors and Collaborators

AstraZeneca

Investigators

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

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01725230 History of Changes
• Other Study ID Numbers: D4300C00039
• First Posted: November 12, 2012
• Last Update Posted: February 4, 2013
• Last Verified: January 2013

Keywords provided by AstraZeneca:

Fostamatinib,; simvastatin,; rosuvastatin,; Phase I,; Healthy Subjects,; Pharmacokinetics

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Rosuvastatin Calcium; Simvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors