Clinical trial NCT01207089: To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral Administration of AZD8329
Official title: A Phase I, Single Centre, Single-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AZD8329 After Administration of Multiple Ascending Doses in Abdominally Obese But Otherwise Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Overweight
Healthy
Male
Keywords: Safety
tolerability
PK
healthy
overweight
obese
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-09-22
Enrollment: 45
Sex: MALE
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Detailed description: A Phase I, Single Centre, Single-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of oral AZD8329 after Administration of Multiple Ascending Doses in Abdominally Obese but otherwise Healthy Male Subjects

Eligibility criteria: Inclusion Criteria:

* 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

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.
* 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

Primary outcomes:
measure: Safety variables (adverse events).
timeFrame: Adverse events day -1
measure: Safety variables (adverse events).
timeFrame: Adverse events will colletected entire study
measure: Safety variables (clinical laboratory assessments).
timeFrame: Clinical labs day 1
measure: Safety variables (clinical laboratory assessments).
timeFrame: Day 4
measure: Safety variables (clinical laboratory assessments).
timeFrame: Day 8
measure: Safety variables (clinical laboratory assessments).
timeFrame: Day 12
measure: Safety variables (clinical laboratory assessments).
timeFrame: Clinical labs at follow up
measure: Safety variables (adverse events)
timeFrame: Adverse events will colletected entire study
measure: Safety variables (vital signs)
timeFrame: vital signs every hour during day 1
measure: Safety variables (physical examination)
timeFrame: performed at screening
measure: Safety variables (vital signs)
timeFrame: Vital Signs every hr during day 12
measure: Safety variables (physical examination)
timeFrame: Performed at follow up
measure: Safety variables (telemetry)
timeFrame: telemetry for 24hr. post dose day 1
measure: Safety variables (telemetry)
timeFrame: telemetry for 24hr. post dose day 12
measure: Safety variables (digital electrocardiograms (dECGs))
timeFrame: dECG during 5min, 13 times 24 hr after dose day 1
measure: Safety variables (digital electrocardiograms (dECGs))
timeFrame: dECG during 5min, 13 times 24 hr after dose day 12
measure: Safety variables (safety 12-lead paper electrocardiograms (pECG))
timeFrame: pECG at screening
measure: Safety variables (safety 12-lead paper electrocardiograms (pECG))
timeFrame: pECG at follow up
measure: Safety variables (clinical laboratory assessments).
timeFrame: clinical labs at screening
measure: Safety variables (clinical laboratory assessments).
timeFrame: clinical labs day -3
Secondary outcomes:
measure: Pharmacokinetics Plasma and urine concentrations of AZD8329 and plasma and urine pharmacokinetics parameters
timeFrame: Information will be collected during day -1, day 1, 2, 3 and 12
measure: Pharmacodynamic 11-βHSD1 enzyme activity in adipose tissue
timeFrame: Information will be collected from the time of day -1 throuout the study
measure: Pharmacodynamic 11-βHSD1 enzyme activity in the liver by measuring prednisolone generation
timeFrame: Information will be collected from day -1 to follow up
measure: To assess the effect on insulin after multiple doses of AZD8329
timeFrame: Information will be collected from day -2 to follow up
measure: To assess the effect on glucose after multiple doses of AZD8329
timeFrame: Information will be collected from day -2 to follow up
measure: To assess the effect on lipid variables after multiple doses of AZD8329
timeFrame: Information will be collected from day -2 to follow up
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Dr. Jan Eriksson
role: STUDY_CHAIR
affiliation: AstraZeneca
name: Dr. Mirjana Kujacic
role: STUDY_DIRECTOR
affiliation: Quintiles Drug Research Unit at Guy's Hospital
name: Dr. James Ritter
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.