Clinical trial NCT01469923: To Assess the Safety, Tolerability, Pharmacokinetics and Pharmakodynamics of AZD2820 After Multiple Ascending Doses
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Obesity
Keywords: Phase 1
obese
healthy male volunteers
multiple doses
dose escalation
pharmacokinetics
pharmakodynamics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-11-10
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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 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

Primary outcomes:
measure: Description of the safety and tolerability profile of AZD2820 in terms of adverse events.
timeFrame: From baseline, defined as day 1 of dosing, up to day 29
measure: Description of the safety and tolerability profile of AZD2820 in terms of labolatory data ( clinical chemistry, haematology and urinalisys).
timeFrame: From baseline, defined as one day prior first dose, up to day 28.
measure: 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).
timeFrame: From baseline, defined as one day prior first dose, up to day 29.
measure: Description of the safety and tolerability profile of AZD2820 in terms of total immunoglobulin levels.
timeFrame: From baseline, defined as one day prior first dose, up to day 44.
measure: Description of the safety and tolerability profile of AZD2820 in terms of safety electrocardiogram (ECG).
timeFrame: From baseline, defined as last pre dose measurement, up to day 28.
measure: Description of the safety and tolerability profile of AZD2820 in terms of digital electrocardiogram (ECG).
timeFrame: From baseline, defined as assessment at screening visit and day 1 of dosing.
measure: Description of the safety and tolerability profile of AZD2820 in terms of electroencephalography (EEG).
timeFrame: From baseline, defined as mean value of the 10 minutes recording prior first dose up to 7th day of dosing.
measure: Description of the safety and tolerability profile of AZD2820 in terms of Columbia-Suicide Severity Rating Scale (C-SSRS).
timeFrame: From baseline, defined as one day prior first dose, up to day 12th of dosing.
measure: Description of the safety and tolerability profile of AZD2820 in terms of skin pigmentation.
timeFrame: From baseline, defined as one day before first dose, up to day 29.
measure: Description of the safety and tolerability profile of AZD2820 in terms of Penile erection (measured by Rigiscan).
timeFrame: From baseline, defined as one day before first dose, up 12th day of dosing.
measure: Description of the safety and tolerability profile of AZD2820 in terms of physical examination.
timeFrame: From baseline, defined as two days prior first dose, up to day 29.
Secondary outcomes:
measure: Change in total caloric intake from baseline.
timeFrame: From baseline, defined as one day prior first dose to end of treatement which is day 15.
measure: Description of the PK profile of AZD2820 in terms of Cmax, AUC(0-tau), AUC(0-t), AUC, (t1/2lz, h).
timeFrame: 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.
measure: Description of PK profile of AZD2820 in terms of (Css,max, nmol/L), AUCss,(0-tau), (t1/2lz).
timeFrame: 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.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research site
Study officials:
affiliation: QLON
name: James Ritter, BM BCH, MRCP, FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca Mölndal, Sweden
name: Mark Berner Hansen, PHD
role: STUDY_DIRECTOR
affiliation: AstraZeneca Mölndal, Sweden
name: Mirjana Kujacic, PHD
role: STUDY_CHAIR
References: