Clinical trial NCT01926366: AZD6423 SAD/MAD Study in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers.
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-08-20
Enrollment: 175
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of the safety and tolerability of AZD6423 in healthy subjects via adverse events
timeFrame: From Baseline up to 18 days
measure: Assessment of the safety and tolerability of AZD6423 in healthy subjects via EEG
timeFrame: From Baseline up to 6 days
measure: Assessment of the safety and tolerability of AZD6423 in healthy subjects via ECG.
timeFrame: From Baseline up to 18 days
measure: 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
timeFrame: From Baseline up to 18 days
measure: Assessment of the safety and tolerability of AZD6423 in healthy subjects via clinical laboratory tests (chemistry, hematology and urinalysis).
timeFrame: From Baseline up to 18 days
measure: Assessment of the safety and tolerability of AZD6423 in healthy subjects via psychiatric assessments.
timeFrame: From Baseline up to 18 days
measure: Assessment of the safety and tolerability of AZD6423 in healthy subjects via neurological exams.
timeFrame: From Baseline up to 18 days
measure: Assessment of the safety and tolerability of AZD6423 in healthy subjects via physical exams.
timeFrame: From Baseline up to 18 days
Secondary outcomes:
measure: 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).
timeFrame: From Baseline up to 7 days
measure: Assessment of the pharmacodynamics of AZD6423 in terms of the relationship between plasma concentration of AZD6423 and EEG
timeFrame: From Baseline up to 7 days
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
affiliation: California Clinical Trials
name: David Han, M.D.
role: PRINCIPAL_INVESTIGATOR
References: