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

NCT01457807 | Completed Phase 1

• 1 other identifier: D0490C00003
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

Phase 1; Parkinson's disease; pharmacodynamic; biomarkers; pharmacokinetics; extended release formulation

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (1)

• 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

Study Arms (3)

1

EXPERIMENTAL

AZD3241 300mg extended release formulation 1

Drug: AZD3241 ER formulation 1; Drug: AZD3241 Alternative titration scheme with formulation 1 or 2

2

EXPERIMENTAL

AZD3241 300mg extended release formulation 2

Drug: AZD3241 Alternative titration scheme with formulation 1 or 2

3

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

AZD3241 ER formulation 1 DRUG

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

1

Placebo DRUG

Placebo will be administered with the same intervention scheme as intervention 1 and 2

3

AZD3241 Alternative titration scheme with formulation 1 or 2 DRUG

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

Also known as: This titration scheme will only be used if ER formulations 1 or 2 are not well tolerated

1; 2

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research site

London, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Darren Wilbraham, MBBS, DCPSA

  Quintiles drug research unit, 6 Newcomen Street, SE1 1YR

  PRINCIPAL INVESTIGATOR

• Bjorn Paulsson, MD, PHD

  Astra Zeneca, Sodertalje, Sweden

  STUDY DIRECTOR

• Bo Fransson, MD, PHD

  Astra Zeneca, Sodertalje, Sweden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2011
• First Posted: October 24, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: August 17, 2012

Record last verified: 2012-08

Locations

GB (1)