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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Placebo Comparator |
| |
| 2 | Experimental | AZD8329 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD8329 | Drug | AZD8329 Oral Solution 20mg/ml |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26218540 | Derived | 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. |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| C000589241 | 4-(4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl)benzoic acid |
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| Drug |
Placebo AZD8329 Oral Solution |
|
| 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 |
| 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 |
| To assess the effect on lipid variables after multiple doses of AZD8329 | Information will be collected from day -2 to follow up |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |