A Single Dose Study to Assess the Safety, Effects, and Blood and Urine Drug Levels of AZD3293 in Healthy Subjects
|ClinicalTrials.gov Identifier: NCT01739647|
Recruitment Status : Completed
First Posted : December 3, 2012
Last Update Posted : August 27, 2013
|Condition or disease||Intervention/treatment||Phase|
|Healthy Young Volunteers Healthy Elderly Volunteers||Drug: AZD3293 Drug: Placebo||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||72 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Effect on Biomarkers of AZD3293 Including an Open-Label Food Effect Group in Healthy Male and Non-Fertile Female Volunteers|
|Study Start Date :||December 2012|
|Primary Completion Date :||May 2013|
|Study Completion Date :||May 2013|
Up to 11 sequential cohorts of healthy young and healthy elderly subjects are planned, with single ascending doses ranging from 1mg to a maximum of 1000mg
Placebo Comparator: Placebo
Placebo given (2 subjects in each cohort)
- Adverse event monitoring. [ Time Frame: From baseline up to 10 days. ]
- Assessment of vital signs and physical examination. [ Time Frame: From baseline up to 10 days. ]The vital signs of body temperature, blood pressure and pulse are going to be measured.
- Clinical laboratory tests: hematology. [ Time Frame: From baseline up to 10 days. ]
- Clinical laboratory tests: urine analysis. [ Time Frame: From baseline up to 10 days. ]
- Evaluation of 12-lead digital electrocardiogram (ECG). [ Time Frame: From baseline up to 10 days. ]QT/QTc interval, rhythm, rate, morphology is going to be measured.
- Assessment of telemetry. [ Time Frame: From baseline up to 10 days. ]As reported by investigator.
- Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: From baseline up to 10 days. ]Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.
- Pharmacokinetics (PK) in the terms of AUC, AUC(0-t), AUC(0-24). [ Time Frame: Up 4 days ]Where (AUC(0-t)) is area under the plasma concentration-time curve from zero to the last measurable concentration and (AUC(0-24)) area under the plasma concentration-time curve from zero to 24 hours post-dose.
- Investigation on the effect of AZD3293 on biomarkers relevant for Pharmacodynamics in plasma. [ Time Frame: Up to 4 days. ]
Biomarker PD Aβ (1-40, 1-42) parameters are:
- Maximum observed plasma concentration (Cmax)
- Time to Cmax (tmax)
- Minimum observed plasma concentration (Cmin)
- Minimum observed plasma concentration below the individual healthy volunteer baseline (pre-dose biomarker concentration prior to dosing) (ΔCmin)
- Time to Cmin (tmin)
- Duration (T) of concentration below individual healthy volunteer baseline (BBL), if appropriate for the data (tBBL)
- Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC(0-t))
- Area under the plasma concentration-time curve from zero to 24 hours post dose (AUC(0-24))
- Area under the plasma biomarker concentration curve from time zero to 24 hour that is below individual healthy volunteer baseline (ΔAUC(0-24)).
- Investigation of the potential influence of food on Pharmacokinetics (PK) following a single dose of AZD3293. [ Time Frame: Up to 4 days. ]Pharmacokinetics (PK) in the terms of plasma Cmax and AUC.
- Investigation of the relationship between Pharmacokinetics (PK) and Pharmacodynamics (PD) of AZD3293. [ Time Frame: Up to 4 days. ]The Pharmacokinetics (PK) variables may be plasma concentrations or summary measurements such as Cmax or AUC. The Pharmacodynamics (PD) variables may include biomarkers in plasma such as Aβ (1-40, 1-42) or exploratory PD biomarkers, or safety variables.
- Pharmacokinetics assessment in the terms of fu (%) (fraction of unbound AZD3293 and AZ13569724 in plasma). [ Time Frame: Up to 4 days. ]
- Pharmacokinetics in the terms of Cmax (Maximum observed plasma concentration) and tmax (Time to Cmax ). [ Time Frame: Up to 4 days. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01739647
|United States, Maryland|
|Baltimore, Maryland, United States|
|Study Director:||Robert C Alexander, MD||AstraZeneca|
|Principal Investigator:||Ronald Goldwater, MD||Parexel|