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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01457807
• Date of registration: 10/10/2011
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: To Assess the Effect of Administration of 2 Formulation of AZD3241 on Blood Concentration in Healthy Volunteers
• Scientific title: 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
• Date of first enrolment: November 2011
• Target sample size: 24
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01457807
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: Bo Fransson, MD, PHD
• Affiliation: Astra Zeneca, Sodertalje, Sweden

• Name: Bjorn Paulsson, MD, PHD
• Affiliation: Astra Zeneca, Sodertalje, Sweden

• Name: Darren Wilbraham, MBBS, DCPSA
• Affiliation: Quintiles drug research unit, 6 Newcomen Street, SE1 1YR

Key inclusion & exclusion criteria

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.



Age minimum: 30 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Drug: AZD3241 ER formulation 1

Drug: Placebo

Drug: AZD3241 Alternative titration scheme with formulation 1 or 2

Primary Outcome(s)

t½?z,ss: Half-life of terminal elimination phase at steady state. [Time Frame: 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 [Time Frame: Day 1 until 24 hours post last dose (administered on the morning of Day 8)]

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. [Time Frame: 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] [Time Frame: 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. [Time Frame: Day 1 until 24 hours post last dose (administered on the morning of Day 8)]

?z,ss: Terminal elimination rate constant at steady state. [Time Frame: 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. [Time Frame: 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. [Time Frame: 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. [Time Frame: Day 1 until 24 hours post last dose (administered on the morning of Day 8)]

Secondary Outcome(s)

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. [Time Frame: Day 1 to Day 8]

Secondary ID(s)

D0490C00003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors