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

NCT01725230 | Completed Phase 1

• 1 other identifier: D4300C00039
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Rheumatoid Arthritis

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

Study Arms (2)

Rosuvastatin

EXPERIMENTAL

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; Drug: Rosuvastatin

Simvastatin

EXPERIMENTAL

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; Drug: Simvastatin

Interventions

Fostamatinib DRUG

100-mg tablet

Rosuvastatin; Simvastatin

Rosuvastatin DRUG

20-mg tablet

Rosuvastatin

Simvastatin DRUG

40-mg tablet

Simvastatin

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
• 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 .

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 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Overland Park, Kansas, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

fostamatinib; Rosuvastatin Calcium; Simvastatin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds

Study Officials

• David Mathews, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2012
• First Posted: November 12, 2012
• Study Start: November 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: February 4, 2013

Record last verified: 2013-01

Locations

US (1)