Clinical trial NCT02248818: AZD8108 SAD/MAD in Healthy Volunteers
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AZD8108 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-09-25
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: 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 AZD8108 in healthy volunteers. The study includes an up to 28-day screening period, an in-house period during which AZD8108 or placebo will be administered orally as a solution, and a 4- to 10-day follow-up period after discharge.

Detailed description: In Part 1 of the study (single ascending dose portion), approximately 32 subjects will be randomly assigned. Eight (8) subjects will be randomized in each of 4 dosage-level cohorts (AZD8108 or placebo). Within each cohort, 6 subjects will be randomized to receive AZD8108 and 2 subjects will be randomized to receive placebo. Each subject will receive only one dose of either AZD8108 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 AZD8108 and 2 subjects will be randomized to receive placebo. Each subject will receive twelve doses of either AZD8108 or placebo

Eligibility criteria: Inclusion 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. Men and postmenopausal or surgically sterile women age 18-55 years inclusive. 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.

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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: Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal
timeFrame: Day -1 to 7 days after last dose
measure: Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108
timeFrame: Pre-dose,5,15,30 min, 1,1.5,2,3,4,6,8,10,12,14,16,24,48,(72 SAD only) hr after day 1 dose
measure: Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hour), AZD6765 MAD Day 6 Dose of AZD8108
timeFrame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose
measure: Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 MAD Day 12 Dose of AZD8108
timeFrame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48, 72 hr after Day 12 dose
measure: Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hours), AZD6765 After DAY 12 Dose of AZD8108
timeFrame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16, and 24 hours after dose
measure: Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108
timeFrame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,25,48,972 SAD only)hr after Day 1 dose
measure: Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 6 Dose of AZD8108
timeFrame: Pre-dose, 5,15.30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose
measure: Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 12 Dose of AZD8108
timeFrame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,72 hr after Day 12 dose
Secondary outcomes:
measure: Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108
timeFrame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,(72 SAD only) hr after day 1 dose
measure: Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108
timeFrame: Collection 0-6, 6-12,12-24, 24-48, (48-72 SAD only) hy after Day 1 dose
measure: Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (MAD) After Day 12 Dose of AZD8108
timeFrame: Collection 0-6, 0-12, 12-24, 24-48, 48-72 hr after Day 12 dose
measure: Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Day 12 (MAD) Dose of AZD8108
timeFrame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,72 hours after Day 12 dose
measure: Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD
timeFrame: Day 12 compared to Day 1
Other outcomes:
measure: EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction
timeFrame: 8 hours after dose
measure: EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction
timeFrame: 8 hours after dose
measure: EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction
timeFrame: 8 hours after dose
Locations:
city: New York
country: United States
facility: Clinilabs, Inc.
state: New York
Study officials:
affiliation: Clinilabs, Inc.
name: Mina Pastagia, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: