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

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

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.

Study Overview

• Status: Terminated
• Conditions: Obesity
• Intervention / Treatment: Drug: AZD2820; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AZD2820; AZD2820 multiple injections	Drug: AZD2820; Ascending subcutaneous injections of AZD2820 once daily for 14 days in the abdomen
Placebo Comparator: Placebo for AZD2820; Placebo for AZD2820 multiple injections	Drug: Placebo; Ascending subcutaneous injections of placebo for AZD2820 once daily for 14 days in the abdomen

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: James Ritter, BM BCH, MRCP, FRCP, QLON; Study Director: Mark Berner Hansen, PHD, AstraZeneca Mölndal, Sweden; Study Chair: Mirjana Kujacic, PHD, AstraZeneca Mölndal, Sweden

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: November 8, 2011
• First Posted (Estimate): November 10, 2011

Study Record Updates

• Last Update Posted (Estimate): July 24, 2012
• Last Update Submitted That Met QC Criteria: July 23, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; Phase 1; obese; dose escalation; multiple doses; healthy male volunteers; pharmakodynamics
• Other Study ID Numbers: D3870C00002