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

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01196676
First received: August 20, 2010
Last updated: July 29, 2011
Last verified: July 2011
  Purpose

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


Condition Intervention Phase
Bipolar Disorder
Drug: AZD4451
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 [ Time Frame: Screening to end of study. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the pharmacokinetics of single ascending oral doses of AZD4451 by maximum plasma concentration (Cmax). [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Urine will be collectioned for 72 hours post-dose. Pre-dose to 12 hours, 12-24, 24- 48 and 48-72 hours post-dose. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 63
Study Start Date: August 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
AZD4451
Drug: AZD4451
1 mg capsules, 5 mg capsules, and 25 mg capsules
Placebo Comparator: 2
Placebo
Drug: Placebo
1 mg capsules, 5 mg capsules, and 25 mg capsules

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01196676

Locations
United States, Kansas
Research Site
Overland Park, Kansas, United States
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Medical Science Director, AstraZeneca
ClinicalTrials.gov Identifier: NCT01196676     History of Changes
Other Study ID Numbers: D3600C00001
Study First Received: August 20, 2010
Last Updated: July 29, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
AZD4451
Bipolar
depression

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 22, 2014