Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4451 (AZD4451 SAD)

A Phase I, Randomized, Double- Blind, Placebo- Controlled, Single-center Study, to Assess the Safety, Tolerability and Pharmacokinetics of AZD4451 Following Single Ascending Oral Dose Administration in Healthy Subjects

This is a single ascending dose study to assess the safety, tolerability and pharmacokinetics of AZD4451.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: AZD4451; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provide a signed and dated, written informed consent prior to any study specific procedures being performed. including the genetic sampling and analyses. If a volunteer declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the volunteer. The volunteer will not be excluded from other aspects of the study described in this protocol.
• Healthy male and female (of non-childbearing potential) volunteers 18 to 55 years old inclusive with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at screening and on admission to the unit, must not be nursing and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
• Post-menopausal defined as amenorrhoea for at least 12 months following cessation of all exogenous hormonal treatments and with FSH levels in the laboratory defined post-menopausal range
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation Male volunteers should be willing to use barrier contraception for example, condoms and spermicide, from the day of dosing until at least 3 months after dosing with the investigational product.
• Have a body mass index (BMI) between 19 and 30 kg/m2 (BMI <30.5 =30) and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria:

• History of gastrointestinal surgery (other than cholecystectomy or appendectomy) or unintentional rapid weight loss.
• A positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV).
• History of any of the following as judged by the Investigator: History of psychiatric disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders text revision; Medically diagnosed depression in the 6 months prior to dosing; Bipolar disorder; Use of psychoactive medication (including mood stabilizers) in the 6 months prior to dosing; Electroconvulsive therapy in the 6 months prior to dosing; History of seizures 1 year prior to dosing; History of severe dystonic reaction to other drugs.
• History of syncope, fainting or of vasovagal reactions; history of arrhythmias, and/or postural hypotension. The inclusion of volunteers meeting the above criteria may be decided on a case-by-case basis after consultation between the Investigator and AZ CPA physician.
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Drug: Placebo; 1 mg capsules, 5 mg capsules, and 25 mg capsules
Experimental: 1; AZD4451	Drug: AZD4451; 1 mg capsules, 5 mg capsules, and 25 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the safety and tolerability of single ascending oral doses of AZD4451 by assessing AEs, vital signs, physical examinations, neurological examinations clinical laboratory parameters, Columbia Suicide Severity Rating Scale(CSSRS), EEGs and ECGs	Screening to end of study.

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the pharmacokinetics of single ascending oral doses of AZD4451 by maximum plasma concentration (Cmax).	Predose, 30 min, 1 hr, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 18, 24, 30, 48, and 72 hours postdose.
To evaluate and characterize the PK of AZD4451 and its metabolites AZ13263197 and AZ13263195 when given orally in single ascending doses by assessment of drug concentration in urine.	Urine will be collectioned for 72 hours post-dose. Pre-dose to 12 hours, 12-24, 24- 48 and 48-72 hours post-dose.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Mark Smith, AstraZeneca, LP, 1800 Concord Pike, Wilmington, DE; Principal Investigator: Ralph Schutz, Quintiles Phase I Services, 6700 West 115th Street, Overland Park, Kansas 66211

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: August 20, 2010
• First Submitted That Met QC Criteria: September 6, 2010
• First Posted (Estimate): September 8, 2010

Study Record Updates

• Last Update Posted (Estimate): August 1, 2011
• Last Update Submitted That Met QC Criteria: July 29, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: depression; Bipolar; AZD4451
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: D3600C00001