To Assess the Safety, Tolerability, Pharmacokinetics and Pharmakodynamics of AZD2820 After Multiple Ascending Doses

Study Overview
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Brief Summary
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This is a randomised and single-blind, placebo-controlled study to investigate the safety, tolerabilty, pharmacokinetics and pharmacodynamics of repeated and ascending doses of AZD2820 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 AZD2820 after Administration of Multiple Ascending Doses.

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 AZD2820 After Administration of Multiple Ascending Doses

Conditions
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Obesity

Intervention / Treatment
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* Drug: AZD2820
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study specific procedures including the genetic sampling and analyses Obese but otherwise healthy male subjects aged 18 - 45 years with suitable veins for cannulation or repeated venepuncture Male subjects should be willing to use barrier contraception ie, condoms, from the first day of dosing until 3 months after the last dose of investigational product Have a body mass index (BMI) between 27 and 40 kg/m2 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 in the stud A history of erectile dysfunction or anatomic abnormality of the penis (eg, cavernosal fibrosis, Peyronie's disease, or plaques) which interferes with normal erectile function Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome 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 AZD2820 Any clinically significant abnormalities in clinical chemistry, haematology (including eosinophilia) or urinalysis results as judged by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 |
| --- | --- |
| Active Comparator: AZD2820<br>AZD2820 multiple injections | Drug: AZD2820<br>* Ascending subcutaneous injections of AZD2820 once daily for 14 days in the abdomen<br>|
| Placebo Comparator: Placebo for AZD2820<br>Placebo for AZD2820 multiple injections | Drug: Placebo<br>* Ascending subcutaneous injections of placebo for AZD2820 once daily for 14 days in the abdomen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the safety and tolerability profile of AZD2820 in terms of adverse events. | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis. | From baseline, defined as day 1 of dosing, up to day 29 | 
| Description of the safety and tolerability profile of AZD2820 in terms of labolatory data ( clinical chemistry, haematology and urinalisys). | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis. | From baseline, defined as one day prior first dose, up to day 28. | 
| Description of the safety and tolerability profile of AZD2820 in terms of vital signs ( pulse, systolic and diastolic blood preassure ( SBP, DBP and 24h ambulatory BP), body temperature). | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis. | From baseline, defined as one day prior first dose, up to day 29. | 
| Description of the safety and tolerability profile of AZD2820 in terms of total immunoglobulin levels. | Number of subjects with immunoglobuline level outsite of reference range. No formal statistical tests will be performed. Abnormalities will be listed without statistical analysis. | From baseline, defined as one day prior first dose, up to day 44. | 
| Description of the safety and tolerability profile of AZD2820 in terms of safety electrocardiogram (ECG). | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis | From baseline, defined as last pre dose measurement, up to day 28. | 
| Description of the safety and tolerability profile of AZD2820 in terms of digital electrocardiogram (ECG). | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis. The QT correction factor will be based on the Fridericia's formula. | From baseline, defined as assessment at screening visit and day 1 of dosing. | 
| Description of the safety and tolerability profile of AZD2820 in terms of electroencephalography (EEG). | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis. | From baseline, defined as mean value of the 10 minutes recording prior first dose up to 7th day of dosing. | 
| Description of the safety and tolerability profile of AZD2820 in terms of Columbia-Suicide Severity Rating Scale (C-SSRS). | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis. | From baseline, defined as one day prior first dose, up to day 12th of dosing. | 
| Description of the safety and tolerability profile of AZD2820 in terms of skin pigmentation. | No formal statistical test will be performed. | From baseline, defined as one day before first dose, up to day 29. | 
| Description of the safety and tolerability profile of AZD2820 in terms of Penile erection (measured by Rigiscan). | No formal statistical test will be performed. | From baseline, defined as one day before first dose, up 12th day of dosing. | 
| Description of the safety and tolerability profile of AZD2820 in terms of physical examination. | No formal statistical test will be performed. Abnormalities will be listed without statistical analysis. | From baseline, defined as two days prior first dose, up to day 29. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total caloric intake from baseline. | Change from baseline will be measured after each meal and then grafically presented. | From baseline, defined as one day prior first dose to end of treatement which is day 15. | 
| Description of the PK profile of AZD2820 in terms of Cmax, AUC(0-tau), AUC(0-t), AUC, (t1/2lz, h). | Maximum drug plasma concentration (Cmax), Area under the drug plasma concentration-time curve from zero to the end of the dosing interval (AUC(0-tau), Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC(0-t)), Area under the plasma concentration time curve from zero to infinity (AUC), Terminal half-life (t1/2lz, h). | Day 1, PK samples collected post-dese at 20 min, 40 min, 1hr, 1.20hr, 1.40hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 18hrs and 24hrs. | 
| Description of PK profile of AZD2820 in terms of (Css,max, nmol/L), AUCss,(0-tau), (t1/2lz). | Maximum plasma concentration at steady state (Css,max, nmol/L), Area under the plasma concentration-time curve from zero to the end of the dosing interval at steady state (AUCss,(0-tau)), Terminal half-life (t1/2lz). | Day 7, PK samples collected post-dese at 20 min, 40 min, 1hr, 1.20hr, 1.40hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 18hrs and 24hrs. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, obese, healthy male volunteers, multiple doses, dose escalation, pharmacokinetics, pharmakodynamics