Clinical trial NCT01889160: Study to Investigate the Safety Profile of AZD4721 After Single Doses at Different Dose Levels
Official title: A Phase I Single-blind, Randomised, Placebo-controlled, Single-centre Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral AZD4721 Solution After Single Ascending Doses, and to Compare the Oral Bioavailability of Single Doses of Solution and Suspension in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety,Plasma AUC and Cmax, Plasma AUC 0-t, t1/2λz, and Tmax
Keywords: Healthy volunteers, Phase 1
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-06-28
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Study to investigate the safety profile of AZD4721 after single doses at different dose levels

Detailed description: A study to investigate safety and tolerability of single ascending doses of AZD4721 given to healthy volunteers. Including a bioequivalence part to compare a solution of AZD4721 with a suspension.

Eligibility criteria: Inclusion Criteria:

1. Healthy male and/or female Caucasian (neither Black/African American nor Japanese) volunteers aged 18-50 years. ("Healthy" is as determined by medical history and physical examination, clinical laboratory parameters, and ECG )
2. Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of nonchildbearing potential
3. Volunteers should have a BMI between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).

Exclusion Criteria:

1. History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate
2. Current smokers or those who have smoked or used nicotine products within the previous 3 months

2.Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to Visit 1, as determined by the Investigator

4. Other latent or chronic infections (eg, recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection) in previous 90 days, or history of skin abscesses within the previous

Primary outcomes:
measure: Description of the safety profile in terms of Adverse events; blood pressure, heart rate and body temperature; electrocardiograms; clinical chemistry; haematology assessments, including serial blood neutrophil count
timeFrame: From Screening to follow up ( maximum 7 weeks)
Secondary outcomes:
measure: Description of the pharmacokinetic(PK) profile for in terms of: observed maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), terminal rate constant (λz), terminal half-life (t½ z).
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
measure: Description of the pharmacokinetic(PK) profile for in terms of: area under the plasma concentration-time curve from time zero to 24 hours after dosing (AUC(0-24)), from time zero to the time of last quantifiable concentration (AUC(0 last))
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
measure: Description of the pharmacokinetic(PK) profile for in terms of from time zero extrapolated to infinity (AUC), apparent clearance for parent drug estimated as dose divided by AUC (CL/F; AZD4721 only)
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
measure: Description of the pharmacokinetic(PK) profile in terms of apparent volume of distribution during terminal phase (Vz/F; AZD4721 only), mean residence time (MRT, AZD4721 only), lag-time (T-lag, AZD4721 only), dose-normalized AUC (AUC/D) and Cmax (Cmax/D)
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
measure: Description of the pharmacokinetic(PK) profile for in terms of effective half-life (t½(eff)), time of last quantifiable concentration (tlast), predicted accumulation ratio (Rac,pred)
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
measure: Description of the pharmacokinetic(PK) profile for in terms of the time interval and number of data points included in the log-linear regression to determine terminal half-life (z,Interval and z,N)
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
measure: Description of the pharmacokinetic(PK) profile for in terms of the regression coefficient for calculation of the terminal rate constant (Rsq), and the percentage of area under the curve to infinity obtained by extrapolation (%AUCex).
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
measure: Description of the pharmacokinetic(PK) profile for in terms of the metabolic ratios (ratio of metabolite to parent) for AUC and Cmax (MRAUC and MRCmax)
timeFrame: Sample taken predose, 1, 3, 5, 7, 9, 13, 18, 24, 36, 48, 72, 96, 144, 216 hours postdose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Quintiles London UK
name: James Ritter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Astrazeneca Molndal, Sweden
name: Bengt Larsson, MD
role: STUDY_DIRECTOR
affiliation: Astrazeneca UK
name: Stuart Oliver, MD
role: STUDY_CHAIR
References: