AZD6423 SAD/MAD Study in Healthy Volunteers (AZD6423)

A Randomized, Double-Blind, Third-Party-Unblinded, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AZD6423 in Healthy Volunteers

This is a randomized, double-blind, placebo-controlled study of single and multiple ascending dosage levels of AZD6423 in healthy volunteers. The study includes an up to 28-day screening period, an in-house period during which AZD6423 or placebo will be administered IV, and a 4- to 10-day follow-up period after discharge.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers.
• Intervention / Treatment: Drug: AZD6423; Drug: Placebo

Detailed Description

In Part 1 of the study (single ascending dose portion), approximately 40 subjects will be randomly assigned. Eight (8) subjects will be randomized in each of 5 dosage-level cohorts (AZD6423 or placebo). Within each cohort, 6 subjects will be randomized to receive AZD6423 and 2 subjects will be randomized to receive placebo. Each subject will receive only one dose of either AZD6423 or placebo on Day 1. In Part 2 of the study (multiple ascending dose portion), approximately 24 subjects will be randomly assigned. Eight (8) subjects will be randomized in each of 3 dosage-level cohorts. Within each cohort, 6 subjects will be randomized to receive AZD6423 and 2 subjects will be randomized to receive placebo. Each subject will receive three doses of either AZD6423 or placebo.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must understand the nature of the study and must provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-specific procedures.
2. All male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 15 days after dose administration. A male subject is considered biologically capable of having children even if his sexual partner is sterile or using contraceptives.
3. Subjects must have a body mass index (BMI) between 19 and 30, inclusive and weigh between 50kg and 100kg inclusive.
4. Subjects must be fluent in English.

Exclusion Criteria:

1. A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, respiratory, immunologic, hematologic, dermatologic, or neurologic abnormality.
2. A clinically significant abnormality on physical examination, neurological examination, EEG, ECG, vital signs or laboratory evaluations at screen or between screen and dose administration.
3. A history of seizure.
4. A history of head trauma, including closed head injury with loss of consciousness.
5. Any history of suicide attempt or suicidal behavior, or, in the opinion of the investigator, clinically significant risk of suicide or violent behavior.
6. Urine drug screen positive for a drug of abuse
7. A family history of schizophrenia, schizoaffective disorder, or psychosis in first degree relatives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: AZD6423; Subjects will participate in 1 of 8 groups and receive single or multiple doses of AZD6423 or matching placebo. In each group 6 subjects will receive AZD6423 and 2 subjects will receive matching placebo.	Drug: AZD6423; Drug: AZD6423 Single or Multiple doses via infusion.
Placebo Comparator: Placebo to match AZD6423; Subjects will participate in 1 of 8 groups and receive single or multiple doses of AZD6423 or matching placebo. In each group 6 subjects will receive AZD6423 and 2 subjects will receive matching placebo.	Drug: Placebo; Placebo to match AZD6423 Single or Multiple doses of matching placebo delivered via infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the safety and tolerability of AZD6423 in healthy subjects via adverse events	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 18 days
Assessment of the safety and tolerability of AZD6423 in healthy subjects via EEG	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 6 days
Assessment of the safety and tolerability of AZD6423 in healthy subjects via ECG.	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 18 days
Assessment of the safety and tolerability of AZD6423 in healthy subjects via vital signs (blood pressure and pulse). as well as body temperature and weight	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 18 days
Assessment of the safety and tolerability of AZD6423 in healthy subjects via clinical laboratory tests (chemistry, hematology and urinalysis).	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 18 days
Assessment of the safety and tolerability of AZD6423 in healthy subjects via psychiatric assessments.	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 18 days
Assessment of the safety and tolerability of AZD6423 in healthy subjects via neurological exams.	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 18 days
Assessment of the safety and tolerability of AZD6423 in healthy subjects via physical exams.	The primary objectives of this study are to assess the safety and tolerability of single and multiple ascending dosage levels of AZD6423 versus placebo in healthy volunteers.	From Baseline up to 18 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the PK profile for AZD6423 in terms of: observed maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), terminal rate constant (λz), terminal half-life (t½ z), and area under the curve (AUC).	Secondary objectives are to assess the pharmacokinetics and pharmacodynamics of AZD6423 in healthy volunteers.	From Baseline up to 7 days
Assessment of the pharmacodynamics of AZD6423 in terms of the relationship between plasma concentration of AZD6423 and EEG	Secondary objectives are to assess the pharmacokinetics and pharmacodynamics of AZD6423 in healthy volunteers.	From Baseline up to 7 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: David Han, M.D., California Clinical Trials

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: August 12, 2013
• First Submitted That Met QC Criteria: August 19, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Estimate): April 4, 2014
• Last Update Submitted That Met QC Criteria: April 3, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: D3521C00001