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

• Description of the safety and tolerability profile of AZD2820 in terms of adverse events. [ Time Frame: From baseline, defined as day 1 of dosing, up to day 29 ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed. Abnormalities will be listed without statistical analysis.
• Description of the safety and tolerability profile of AZD2820 in terms of labolatory data ( clinical chemistry, haematology and urinalisys). [ Time Frame: From baseline, defined as one day prior first dose, up to day 28. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed. Abnormalities will be listed without statistical analysis.
• 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). [ Time Frame: From baseline, defined as one day prior first dose, up to day 29. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed. Abnormalities will be listed without statistical analysis.
• Description of the safety and tolerability profile of AZD2820 in terms of total immunoglobulin levels. [ Time Frame: From baseline, defined as one day prior first dose, up to day 44. ] [ Designated as safety issue: Yes ]
  Number of subjects with immunoglobuline level outsite of reference range. No formal statistical tests will be performed. Abnormalities will be listed without statistical analysis.
• Description of the safety and tolerability profile of AZD2820 in terms of safety electrocardiogram (ECG). [ Time Frame: From baseline, defined as last pre dose measurement, up to day 28. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed. Abnormalities will be listed without statistical analysis
• Description of the safety and tolerability profile of AZD2820 in terms of digital electrocardiogram (ECG). [ Time Frame: From baseline, defined as assessment at screening visit and day 1 of dosing. ] [ Designated as safety issue: Yes ]
  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.
• Description of the safety and tolerability profile of AZD2820 in terms of electroencephalography (EEG). [ Time Frame: From baseline, defined as mean value of the 10 minutes recording prior first dose up to 7th day of dosing. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed. Abnormalities will be listed without statistical analysis.
• Description of the safety and tolerability profile of AZD2820 in terms of Columbia-Suicide Severity Rating Scale (C-SSRS). [ Time Frame: From baseline, defined as one day prior first dose, up to day 12th of dosing. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed. Abnormalities will be listed without statistical analysis.
• Description of the safety and tolerability profile of AZD2820 in terms of skin pigmentation. [ Time Frame: From baseline, defined as one day before first dose, up to day 29. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed.
• Description of the safety and tolerability profile of AZD2820 in terms of Penile erection (measured by Rigiscan). [ Time Frame: From baseline, defined as one day before first dose, up 12th day of dosing. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed.
• Description of the safety and tolerability profile of AZD2820 in terms of physical examination. [ Time Frame: From baseline, defined as two days prior first dose, up to day 29. ] [ Designated as safety issue: Yes ]
  No formal statistical test will be performed. Abnormalities will be listed without statistical analysis.

• Change in total caloric intake from baseline. [ Time Frame: From baseline, defined as one day prior first dose to end of treatement which is day 15. ] [ Designated as safety issue: No ]
  Change from baseline will be measured after each meal and then grafically presented.
• Description of the PK profile of AZD2820 in terms of Cmax, AUC(0-tau), AUC(0-t), AUC, (t1/2lz, h). [ Time Frame: 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. ] [ Designated as safety issue: No ]
  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).
• Description of PK profile of AZD2820 in terms of (Css,max, nmol/L), AUCss,(0-tau), (t1/2lz). [ Time Frame: 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. ] [ Designated as safety issue: No ]
  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).

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.

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.

• Drug: AZD2820
  Ascending subcutaneous injections of AZD2820 once daily for 14 days in the abdomen
• Drug: Placebo
  Ascending subcutaneous injections of placebo for AZD2820 once daily for 14 days in the abdomen

• Active Comparator: AZD2820
  AZD2820 multiple injections
  Intervention: Drug: AZD2820
• Placebo Comparator: Placebo for AZD2820
  Placebo for AZD2820 multiple injections
  Intervention: Drug: Placebo

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