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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Butyrylcholinesterase Deficiency

Intervention / Treatment
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* Drug: AZD8848


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Butyrylcholinesterase deficiency, tolerability, safety, AZD8848, pharmacokinetics, pharmacodynamics, BChE deficient subjects and matched control subject