A Single Dose Study to Assess the Safety, Effects, and Blood and Urine Drug Levels of AZD3293 in Healthy Subjects
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|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|
|Actual Primary Completion Date :||May 2013|
|Actual 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. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|