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

NCT01469923 | Terminated Phase 1

• 1 other identifier: D3870C00002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Keywords

Phase 1; obese; healthy male volunteers; multiple doses; dose escalation; pharmacokinetics; pharmakodynamics

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (3)

• Change in total caloric intake from baseline.

  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).

  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).

  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.

Study Arms (2)

AZD2820

ACTIVE COMPARATOR

AZD2820 multiple injections

Drug: AZD2820

Placebo for AZD2820

PLACEBO COMPARATOR

Placebo for AZD2820 multiple injections

Drug: Placebo

Interventions

AZD2820 DRUG

Ascending subcutaneous injections of AZD2820 once daily for 14 days in the abdomen

AZD2820

Placebo DRUG

Ascending subcutaneous injections of placebo for AZD2820 once daily for 14 days in the abdomen

Placebo for AZD2820

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research site

London, United Kingdom

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• James Ritter, BM BCH, MRCP, FRCP

  QLON

  PRINCIPAL INVESTIGATOR

• Mark Berner Hansen, PHD

  AstraZeneca Mölndal, Sweden

  STUDY DIRECTOR

• Mirjana Kujacic, PHD

  AstraZeneca Mölndal, Sweden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: November 10, 2011
• Study Start: March 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 24, 2012

Record last verified: 2012-07

Locations

GB (1)