Clinical trial NCT01645085: A Study to Assess the Bioequivalence of R406 in Healthy Volunteers When Given 100mg and 150 mg of Fostamatinib
Official title: An Open-label, Single-center, Randomized, 4-way Crossover Study to Assess the Bioequivalence of R406 in Healthy Volunteers When 100 and 150mg of Fostamatinib Are Administered as the 13% Drug-loaded Tablet Versus the 38% Drug-loaded Tablet
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: R406
Fostamatinib
Phase I
Healthy Subjects
Pharmacokinetics
Bioequivalence
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-07-20
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: A study in Healthy Volunteers to Compare the Amount of R406 in Blood When Given Different Formulations of Fostamatinib.

Detailed description: An Open-label, Single-center, Randomized, 4-way Crossover Study to Assess the Bioequivalence of R406 in Healthy Volunteers when 100 and 150mg of Fostamatinib are Administered as the 13% Drug-loaded Tablet Versus the 38% Drug-loaded Tablet.

Treatment sequences will be determined using two 2-2 crossover designs in sequence, 1 for treatments A and B, and 1 for treatments C and D. The order of the designs containing AB/BA and CD/DC within the overall design, as well as the order of treatments within each design, will be randomized. This gives a total of 8 possible treatment sequences as follows: ABCD, ABDC, BACD, BADC, CDAB, CDBA, DCAB, DCBA.

Eligibility criteria: Inclusion Criteria:

* Males and nonlactating, non childbearing potential females from 18 to 55 years, inclusive and with a weight of at least 50 kg and BMI between 18 and 30 kg/m2, inclusive
* Females must have a negative pregnancy test at screening and on admission to the study center of each period, must not be lactating and must be of non childbearing potential
* Non childbearing potential can be confirmed by being postmenopausal defined as amenorrhea for a least 12 months following cessation of all exogenous hormonal treatments and with FSH and LH levels in the laboratory-defined postmenopausal range
* Non childbearing potential can be confirmed by documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.

Exclusion Criteria:

* History of any clinically significant disease or disorder, including GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
* Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody
* Known or suspected history of drug abuse, as judge by the investigator
* Any clinically significant abnormalities on 12-lead ECG as judged by the Investigator
* Current smokers, or those who have smoked, used nicotine-containing products, or used smoking cessation treatments within the previous 1 month prior to enrollment

Primary outcomes:
measure: Bioequivalence of R406 when fostamatinib is administered as two 50mg MCC-based 13% drug-loaded tablets versus one 100mg mannitol-based 38% drug-loaded tablet
timeFrame: Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose
measure: Bioequivalence of R406 when fostamatinib is administered as three 50mg MCC-based 13% drug-loaded tablets versus one 150mg mannitol-based 38% drug-loaded tablet
timeFrame: Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose
Secondary outcomes:
measure: AUC for mannitol-based 38% drug-loaded tablets and MCC-based 13% drug-loaded tablets
timeFrame: Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose
measure: Cmax for mannitol-based 38% drug-loaded tablets and MCC-based 13% drug-loaded tablets
timeFrame: Measured at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdoses
measure: Frequency of adverse events
timeFrame: Measured throughout the study and 3 -5 days after discharge from Period 4, approximately 45 days
measure: Severity of adverse events
timeFrame: Measured throughout the study and 3 -5 days after discharge from Period 4, approximately 45 days
Other outcomes:
Locations:
city: Overland Park
country: United States
state: Kansas
Study officials:
affiliation: AstraZeneca
name: Chris O'Brien, MEDICAL SCIENCE DIRECTOR
role: STUDY_DIRECTOR
affiliation: Quintiles, Inc.
name: David Mathews, MD
role: PRINCIPAL_INVESTIGATOR
References: