To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral Administration of AZD8329

NCT01207089 | Completed Phase 1

• 1 other identifier: D2350C00010
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8329 following multiple ascending dose administrations in in overweight to obese but otherwise healthy male subjects.

Conditions

Overweight; Healthy; Male

Keywords

Safety; tolerability; PK; healthy; overweight; obese

Outcome Measures

Primary Outcomes (20)

• Safety variables (adverse events).

  Adverse events day -1

• Safety variables (adverse events).

  Adverse events will colletected entire study

• Safety variables (clinical laboratory assessments).

  Clinical labs day 1

• Safety variables (clinical laboratory assessments).

  Day 4

• Safety variables (clinical laboratory assessments).

  Day 8

• Safety variables (clinical laboratory assessments).

  Day 12

• Safety variables (clinical laboratory assessments).

  Clinical labs at follow up

• Safety variables (adverse events)

  Adverse events will colletected entire study

• Safety variables (vital signs)

  vital signs every hour during day 1

• Safety variables (physical examination)

  performed at screening

• Safety variables (vital signs)

  Vital Signs every hr during day 12

• Safety variables (physical examination)

  Performed at follow up

• Safety variables (telemetry)

  telemetry for 24hr. post dose day 1

• Safety variables (telemetry)

  telemetry for 24hr. post dose day 12

• Safety variables (digital electrocardiograms (dECGs))

  dECG during 5min, 13 times 24 hr after dose day 1

• Safety variables (digital electrocardiograms (dECGs))

  dECG during 5min, 13 times 24 hr after dose day 12

• Safety variables (safety 12-lead paper electrocardiograms (pECG))

  pECG at screening

• Safety variables (safety 12-lead paper electrocardiograms (pECG))

  pECG at follow up

• Safety variables (clinical laboratory assessments).

  clinical labs at screening

• Safety variables (clinical laboratory assessments).

  clinical labs day -3

Secondary Outcomes (6)

• Pharmacokinetics Plasma and urine concentrations of AZD8329 and plasma and urine pharmacokinetics parameters

  Information will be collected during day -1, day 1, 2, 3 and 12

• Pharmacodynamic 11-βHSD1 enzyme activity in adipose tissue

  Information will be collected from the time of day -1 throuout the study

• Pharmacodynamic 11-βHSD1 enzyme activity in the liver by measuring prednisolone generation

  Information will be collected from day -1 to follow up

• To assess the effect on insulin after multiple doses of AZD8329

  Information will be collected from day -2 to follow up

• To assess the effect on glucose after multiple doses of AZD8329

  Information will be collected from day -2 to follow up

Study Arms (2)

1

PLACEBO COMPARATOR

Drug: Placebo

2

EXPERIMENTAL

AZD8329

Drug: AZD8329

Interventions

AZD8329 DRUG

AZD8329 Oral Solution 20mg/ml

2

Placebo DRUG

Placebo AZD8329 Oral Solution

1

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Have a body mass index (BMI) between 27 and 35 kg/m2 and a waist circumference greater than or equal to 102cm.
• Provision of signed and dated, written informed consent prior to any study specific procedures
• Healthy male subjects aged =20 to =50 years with suitable veins for cannulation or repeated venepuncture

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.
• Fasting serum (S)-glucose =7.0 mmol/L or non-fasting S-glucose =11.1 mmol/L at screening.
• Any eating disorder or actively attempting to loose weight within 3 months prior to enrolment

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Publications (1)

• Morentin Gutierrez P, Gyte A, deSchoolmeester J, Ceuppens P, Swales J, Stacey C, Eriksson JW, Sjostrand M, Nilsson C, Leighton B. Continuous inhibition of 11beta-hydroxysteroid dehydrogenase type I in adipose tissue leads to tachyphylaxis in humans and rats but not in mice. Br J Pharmacol. 2015 Oct;172(20):4806-16. doi: 10.1111/bph.13251. Epub 2015 Oct 8.

  PMID: 26218540 DERIVED

MeSH Terms

Conditions

Overweight; Obesity

Interventions

4-(4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl)benzoic acid

Condition Hierarchy (Ancestors)

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

Study Officials

• Dr. Jan Eriksson

  AstraZeneca

  STUDY CHAIR

• Dr. Mirjana Kujacic

  AstraZeneca

  STUDY DIRECTOR

• Dr. James Ritter

  Quintiles Drug Research Unit at Guy's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 14, 2010
• First Posted: September 22, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: May 10, 2011

Record last verified: 2011-05

Locations

GB (1)