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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01469923
First received: September 30, 2011
Last updated: July 23, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Obesity
Drug: AZD2820
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Enrollment: 18
Study Start Date: March 2012
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469923

Locations
United Kingdom
Research site
London, United Kingdom
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01469923     History of Changes
Other Study ID Numbers: D3870C00002
Study First Received: September 30, 2011
Last Updated: July 23, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Phase 1
obese
healthy male volunteers
multiple doses
dose escalation
pharmacokinetics
pharmakodynamics

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on August 21, 2014