Clinical trial NCT00878618: Pharmacokinetics of Extended-Release Test- and Reference Formulations of AZD0837
Official title: A Phase I, Single-Centre, Open, Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of the Extended-Release Test Formulation of AZD0837 Compared to the Extended-Release AZD0837 Reference Formulation After Repeated Dosing in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteers
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-04-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aims of this study are to evaluate the pharmacokinetics, safety and tolerability of the oral doses of the extended-release test- and reference formulations of AZD0837 in healthy volunteers both in fasting and fed conditions.


Eligibility criteria: Inclusion Criteria:

* Healthy subject aged between 18 to 45 years inclusive
* Body mass index (BMI) between 19 to 30 kg/m2 inclusive
* Body weight between 50 to 100 kg inclusive
* Women must be either post-menopausal, permanently sterilised or, if of childbearing potential, must have a negative pregnancy test before intake of study medication and use a reliable form of contraception before and during participation in the study.

Exclusion Criteria:

* Significant illness (including ongoing or history of liver disease), trauma or surgical procedures from 2 weeks before the pre-entry visit until the first administration of Investigational Product
* Clinical significant abnormalities in clinical chemistry, haematology or urinalysis result including positive result on screening tests for serum hepatitis B surface antigen, hepatitis C antibody or HIV or positive F-Hb result pre-entry
* History of bleeding disturbance (including extensive menstrual bleedings) or thrombotic disorder
* Clinically significant medical history, as judged by the investigator, including psychiatric disorders or severe allergies.

Primary outcomes:
measure: To evaluate the pharmacokinetics of AZD0837 and the active metabolite AR-H067637XX for the extended-release test formulation of AZD0837 compared to the ER reference formulation.
timeFrame: Intense PK-sampling during 5 pre- defined study days for PK profiling. In 2 of the study days the subjects will have a breakfast before intake of the Investigational Product.
Secondary outcomes:
measure: To evaluate the PK of the intermediate metabolite AR-H069927XX
timeFrame: Since the metbolite will be evaluated from the AZD0837-samples the time frame is the same as above.
measure: Safety variables (ECG, pulse, blood pressure, safety lab, physical examination, adverse events)
timeFrame: ECG & physical examination at start and end of study. Pulse and blood pressure predose day 1 and every day 2 h post dose. Adverse events collected during the whole study. Safety lab at a few timepoints but APTT will be checked on 4 h post dose on day 1.
measure: Measurement of plasma concentrations of 4 beta-hydroxycholesterol to investigate whether AZD0837 affects the level of CYP3A4
timeFrame: Once predose on day 1, session 1 and once predose on day 5, session 2
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Research Site
Study officials:
affiliation: Quintiles AB, Uppsala, Sweden
name: Elisabeth Edén Eden
role: PRINCIPAL_INVESTIGATOR
References: