To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral Administration of AZD8329

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8329 following multiple ascending dose administrations in in overweight to obese but otherwise healthy male subjects.

Detailed Description
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A Phase I, Single Centre, Single-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of oral AZD8329 after Administration of Multiple Ascending Doses in Abdominally Obese but otherwise Healthy Male Subjects

Official Title
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A Phase I, Single Centre, Single-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AZD8329 After Administration of Multiple Ascending Doses in Abdominally Obese But Otherwise Healthy Male Subjects

Conditions
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Overweight, Healthy, Male

Intervention / Treatment
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* Drug: AZD8329
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index (BMI) between 27 and 35 kg/m2 and a waist circumference greater than or equal to 102cm. Provision of signed and dated, written informed consent prior to any study specific procedures Healthy male subjects aged =20 to =50 years with suitable veins for cannulation or repeated venepuncture Exclusion Criteria: History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate. Fasting serum (S)-glucose =7.0 mmol/L or non-fasting S-glucose =11.1 mmol/L at screening. Any eating disorder or actively attempting to loose weight within 3 months prior to enrolment

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Placebo<br>* Placebo AZD8329 Oral Solution<br>|
| Experimental: 2<br>AZD8329 | Drug: AZD8329<br>* AZD8329 Oral Solution 20mg/ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety variables (adverse events). |  | Adverse events day -1 | 
| Safety variables (adverse events). |  | Adverse events will colletected entire study | 
| Safety variables (clinical laboratory assessments). |  | Clinical labs day 1 | 
| Safety variables (clinical laboratory assessments). |  | Day 4 | 
| Safety variables (clinical laboratory assessments). |  | Day 8 | 
| Safety variables (clinical laboratory assessments). |  | Day 12 | 
| Safety variables (clinical laboratory assessments). |  | Clinical labs at follow up | 
| Safety variables (adverse events) |  | Adverse events will colletected entire study | 
| Safety variables (vital signs) |  | vital signs every hour during day 1 | 
| Safety variables (physical examination) |  | performed at screening | 
| Safety variables (vital signs) |  | Vital Signs every hr during day 12 | 
| Safety variables (physical examination) |  | Performed at follow up | 
| Safety variables (telemetry) |  | telemetry for 24hr. post dose day 1 | 
| Safety variables (telemetry) |  | telemetry for 24hr. post dose day 12 | 
| Safety variables (digital electrocardiograms (dECGs)) |  | dECG during 5min, 13 times 24 hr after dose day 1 | 
| Safety variables (digital electrocardiograms (dECGs)) |  | dECG during 5min, 13 times 24 hr after dose day 12 | 
| Safety variables (safety 12-lead paper electrocardiograms (pECG)) |  | pECG at screening | 
| Safety variables (safety 12-lead paper electrocardiograms (pECG)) |  | pECG at follow up | 
| Safety variables (clinical laboratory assessments). |  | clinical labs at screening | 
| Safety variables (clinical laboratory assessments). |  | clinical labs day -3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Plasma and urine concentrations of AZD8329 and plasma and urine pharmacokinetics parameters |  | Information will be collected during day -1, day 1, 2, 3 and 12 | 
| Pharmacodynamic 11-βHSD1 enzyme activity in adipose tissue |  | Information will be collected from the time of day -1 throuout the study | 
| Pharmacodynamic 11-βHSD1 enzyme activity in the liver by measuring prednisolone generation |  | Information will be collected from day -1 to follow up | 
| To assess the effect on insulin after multiple doses of AZD8329 |  | Information will be collected from day -2 to follow up | 
| To assess the effect on glucose after multiple doses of AZD8329 |  | Information will be collected from day -2 to follow up | 
| To assess the effect on lipid variables after multiple doses of AZD8329 |  | Information will be collected from day -2 to follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, tolerability, PK, healthy, overweight, obese