To Assess the Effect of Administration of 2 Formulation of AZD3241 on Blood Concentration in Healthy Volunteers

A Phase I, Single-centre, Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of Two Different Extended Release Formulations of Tablets of AZD3241 (300 mg) After Administration of Multiple Doses in Healthy Male and Female Volunteers

To evaluate the pharmacokinetics of AZD3241 following multiple administration of 2 new, different extended release formulations of tablets of AZD3241 (300 mg), in relation to the 100 mg extended release tablet used in a previous study and potential food interaction. The safety and tolerability of AZD 3241 will also be investigated as a secondary objective. In addition to these a number of exploratory objectives will be investigated with blood sampling.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: AZD3241 ER formulation 1; Drug: AZD3241 Alternative titration scheme with formulation 1 or 2; Drug: Placebo

Detailed Description

A Phase I, Single-centre, Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of Two Different Extended Release Formulations of Tablets of AZD3241 (300 mg) after Administration of Multiple Doses in Healthy Male and Female Volunteers

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures
• Healthy male or female volunteers aged 30 to 65 years, inclusive, with suitable veins for cannulation or repeated venepuncture
• Female volunteers must have a negative pregnancy test at Screening and on admission to the CPU, must not be lactating and must be of non childbearing potential, confirmed at Screening
• Male volunteers must be willing to use barrier contraception ie, condoms, from the first day of dose administration until 3 months after the last dose of the IP
• Volunteers must have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg

Exclusion Criteria:

• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD3241
• Orthostatic hypotension defined as 25 mmHg decrease in systolic and/or 15 mmHg decrease in diastolic BP as measured at enrolment and/or randomisation
• History of intolerance or hypersensitivity to mannitol
• Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF)>450 ms or shortened QTcF<340 ms or a family history of long QT syndrome
• Abnormal vital signs, after 10 minutes of rest in supine position, defined as any of the following:Systolic BP>140 mmHg., Diastolic BP>90 mmHg., Heart rate<40 or >85 beats per minute.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 3; Placebo	Drug: Placebo; Placebo will be administered with the same intervention scheme as intervention 1 and 2
Experimental: 1; AZD3241 300mg extended release formulation 1	Drug: AZD3241 ER formulation 1; Oral tablets, 100mg bd on Day 1 to Day 2, 200mg bd on Day3, 300mg bd on Day 4 to Day7 and 300mg Once daily on Day 8 with High Fat Breakfast; Drug: AZD3241 Alternative titration scheme with formulation 1 or 2; 50 mg oral dose bd on Day 1, 100 mg oral dose bd on Day 2 and 3, 200 mg oral dose bd on Day 4, 300 mg oral dose bd on Day 5 to 7 and 300 mg once in the morning on Day 8; Other Names: This titration scheme will only be used if ER formulations 1 or 2 are not well tolerated
Experimental: 2; AZD3241 300mg extended release formulation 2	Drug: AZD3241 Alternative titration scheme with formulation 1 or 2; 50 mg oral dose bd on Day 1, 100 mg oral dose bd on Day 2 and 3, 200 mg oral dose bd on Day 4, 300 mg oral dose bd on Day 5 to 7 and 300 mg once in the morning on Day 8; Other Names: This titration scheme will only be used if ER formulations 1 or 2 are not well tolerated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC(0-12),ss: Area under the plasma concentration-time curve from time zero to the end of the 12-hour dosing interval at steady state.	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
AUC(0-12),ss/DN: Area under the plasma concentration-time curve from time zero to the end of the 12-hour dosing interval at steady state observed with the 300 mg ER formulations normalised to a 100 mg dose of AZD3241	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Css,max: Observed maximum plasma concentration at steady state.Css,max/DN Observed maximum plasma concentration at steady state observed with the 300 mg ER formulations normalised to a 100 mg dose of AZD3241.	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Css,min: Observed minimum plasma concentration at steady state.Css,min/DN Observed minimum plasma concentration at steady state observed with the 300 mg ER formulations normalised to a 100 mg dose of AZD3241.	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Css,av: Average plasma concentration during the 12-hour dosing interval at steady state calculated as follows: AUC(0-12),ss/12 h.	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Description of fluctuation at steady-state [(Css,max-Css,min)/Css,av]	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
AUC(0-t),ss: Area under the plasma concentration-time curve from time zero to the last quantifiable time point.	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
λz,ss: Terminal elimination rate constant at steady state.	Day 1 until 24 hours post last dose (administered on the morning of Day 8)
t½λz,ss: Half-life of terminal elimination phase at steady state.	Day 1 until 24 hours post last dose (administered on the morning of Day 8)

Secondary Outcome Measures

Outcome Measure	Time Frame
Description of the safety and tolerability profile in terms of Adverse Events of 8 days of administration of AZD3241, up to steady state (300 mg twice daily), of 2 new, different extended release tablets of AZD3241 (300 mg), including initial titration.	Day 1 to Day 8

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Darren Wilbraham, MBBS, DCPSA, Quintiles drug research unit, 6 Newcomen Street, SE1 1YR; Study Director: Bjorn Paulsson, MD, PHD, Astra Zeneca, Sodertalje, Sweden; Study Chair: Bo Fransson, MD, PHD, Astra Zeneca, Sodertalje, Sweden

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: October 10, 2011
• First Submitted That Met QC Criteria: October 20, 2011
• First Posted (Estimate): October 24, 2011

Study Record Updates

• Last Update Posted (Estimate): August 17, 2012
• Last Update Submitted That Met QC Criteria: August 16, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: biomarkers; pharmacokinetics; Phase 1; Parkinson's disease; pharmacodynamic; extended release formulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: D0490C00003