Study to Investigate the Safety and Tolerability of AZD8848 in Butyrylcholinesterase Deficient Subjects

An Open, Non-controlled, Non-randomised, Parallel-group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of AZD 8848 Administered Intranasally to Male and Female Butyrylcholinesterase Deficient Subjects and to Sex and Age Matched Controls

The purpose of this study is to investigate the safety and tolerability of AZD8848 in Butyrylcholinesterase deficient subjects in comparison with sex and age matched control subjects.

Study Overview

• Status: Completed
• Conditions: Butyrylcholinesterase Deficiency
• Intervention / Treatment: Drug: AZD8848

Detailed Description

An Open, Non-controlled, Non-randomised, Parallel-group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of AZD 8848 Administered Intranasally to Male and Female Butyrylcholinesterase deficient Subjects and to Sex and Age matched Controls

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BChE deficient subjects: The half-live of AZD8848 in plasma should be more than 20 minutes in an in vitro screening test
• Matched control subject: The half-live of AZD8848 in plasma should be less than 2 minutes in an in vitro screening test

Exclusion Criteria:

• Any clinically relevant abnormal findings in physical examination, laboratory assessments, vital signs or ECG
• Present or medical history of cardiovascular disease which, in the opinion of the investigator, may either put subject at risk because of participation in the study or influence the result of the study or the subject's ability to participate in the study
• Family history of autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AZD8848 given to BChE deficient subjects and age & gender matched control subjects	Drug: AZD8848; Nasal spray solution, intranasal, single ascending doses, 1.4 - 60 μg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability will be assessed by a panel of measurements including adverse events (AEs), vital signs, ECG, laboratory variables, physical examination, and clinical inspection of the nose	Immediately prior to administration of the IP (Day 0)
Safety and tolerability will be assessed by a panel of measurements including adverse events (AEs), vital signs, ECG, laboratory variables, physical examination, and clinical inspection of the nose	Repeated assessments during Day 1.
Safety and tolerability will be assessed by a panel of measurements including adverse events (AEs), vital signs, ECG, laboratory variables, physical examination, and clinical inspection of the nose	Repeated assessments during Day 2.

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (concentration of AZD8848 and metabolite in plasma and urine)	Prior to administration of the IP (Day 0) and repeated assessments during the first 48h.
Pharmacodynamics (IL-1Ra in plasma)	Prior to administration of the IP (Day 0) and repeated assessments during the first 48h.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Jesper Sonne, MD, DanTrials ApS, Copenhagen, Denmark; Study Director: Sam Lindgren, MD, PhD, AstraZeneca R&D, Lund, Sweden

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: September 20, 2010
• First Submitted That Met QC Criteria: September 20, 2010
• First Posted (Estimate): September 21, 2010

Study Record Updates

• Last Update Posted (Estimate): August 14, 2015
• Last Update Submitted That Met QC Criteria: August 13, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; pharmacodynamics; Butyrylcholinesterase deficiency; AZD8848; BChE deficient subjects and matched control subject
• Other Study ID Numbers: D0540C00009; EUDract No: 2010-019434-27