Pharmacokinetics of Extended-Release Test- and Reference Formulations of AZD0837

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: AZD0837; Drug: AZD0837

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAB; AZD0837 test- (in session 1) and reference- (in session 2) formulation with heavy breakfast	Drug: AZD0837; Extended-release tablets, test formulation. 2 tablets given in the morning for 6 days; Drug: AZD0837; Extended-release tablets, reference formulation. 2 tablets given in the morning for 6 days
Experimental: HBA; AZD0837 reference- (in session 1) and test- (in session 2) formulation with heavy breakfast	Drug: AZD0837; Extended-release tablets, test formulation. 2 tablets given in the morning for 6 days; Drug: AZD0837; Extended-release tablets, reference formulation. 2 tablets given in the morning for 6 days
Experimental: LAB; AZD0837 test- (in session 1) and reference- (in session 2) formulation with light breakfast	Drug: AZD0837; Extended-release tablets, test formulation. 2 tablets given in the morning for 6 days; Drug: AZD0837; Extended-release tablets, reference formulation. 2 tablets given in the morning for 6 days
Experimental: LBA; AZD0837 reference- (in session 1) and test- (in session 2) formulation with light breakfast	Drug: AZD0837; Extended-release tablets, test formulation. 2 tablets given in the morning for 6 days; Drug: AZD0837; Extended-release tablets, reference formulation. 2 tablets given in the morning for 6 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	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 Outcome Measures

Outcome Measure	Time Frame
To evaluate the PK of the intermediate metabolite AR-H069927XX	Since the metbolite will be evaluated from the AZD0837-samples the time frame is the same as above.
Safety variables (ECG, pulse, blood pressure, safety lab, physical examination, adverse events)	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.
Measurement of plasma concentrations of 4 beta-hydroxycholesterol to investigate whether AZD0837 affects the level of CYP3A4	Once predose on day 1, session 1 and once predose on day 5, session 2

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Elisabeth Edén Eden, Quintiles AB, Uppsala, Sweden

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: March 31, 2009
• First Submitted That Met QC Criteria: April 8, 2009
• First Posted (Estimate): April 9, 2009

Study Record Updates

• Last Update Posted (Estimate): June 3, 2009
• Last Update Submitted That Met QC Criteria: June 2, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Healthy volunteers
• Other Study ID Numbers: D1250C00056