AZD8108 SAD/MAD in Healthy Volunteers

AstraZeneca258 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

258

Conditions

Healthy Volunteers

Interventions

AZD8108DRUG

Drug: AZD8108 Single or Multiple doses administered orally as a solution.

PlaceboDRUG

Placebo to match AZD8108 Single or Multiple doses of matching placebo administered orally as a solution

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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. \- 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.

Locations (1)

Clinilabs, Inc.

New York, New York, United States

Outcomes

Primary Outcomes

Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal

Safety Laboratory - Thyroid Stimulating Hormone participants with laboratory value above the upper limit of normal

Time frame: Day -1 to 7 days after last dose

Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108

Pharmacokinetic : Area under the concentration curve (0 to infinity), AZD6765 after single/first dose of AZD8108

Time frame: 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

Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hour), AZD6765 MAD Day 6 Dose of AZD8108

Pharmacokinetic : Area under the concentration curve (0 to 24 hour), AZD6765 MAD Day 6 dose of AZD8108 Cohort 5 \& 7, Cohort 6 did not reach Day 6

Time frame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose

Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 MAD Day 12 Dose of AZD8108

Pharmacokinetic : Area under the concentration curve (0 to infinity), AZD6765 MAD Day 12 dose of AZD8108 Cohort 5 \& 7, Cohort 6 did not reach Day 12

Time frame: 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

Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hours), AZD6765 After DAY 12 Dose of AZD8108

Pharmacokinetic : Area under the concentration curve (0 to 24 hours), AZD6765 after Day 12 dose of AZD8108 cohort 5 \& 7, Cohort 6 dod not reach Day 12

Time frame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16, and 24 hours after dose

Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108

Pharmacokinetic : Maximum concentration of AZD6765 after single/first dose of AZD8108

Data from ClinicalTrials.gov

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Secondary Outcomes

Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108

Pharmacokinetic: Time to Maximum plasma concentration of AZD6765 after single (SAD) / first (MAD) dose AZD8108

Time frame: 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

Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108

Pharmacokinetic: Fraction of equivalent dose of AZD6765 excreted in urine (SAD) after single dose of AZD8108 (Cohorts 1 - 3)

Time frame: Collection 0-6, 6-12,12-24, 24-48, (48-72 SAD only) hy after Day 1 dose

Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (MAD) After Day 12 Dose of AZD8108

Pharmacokinetic: Fraction of equivalent dose of AZD6765 excreted in urine (MAD) after Day 12 dose of AZD8108 Cohorts 5 \& 7, Cohort 6 did not reach day 12

Time frame: Collection 0-6, 0-12, 12-24, 24-48, 48-72 hr after Day 12 dose

Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Day 12 (MAD) Dose of AZD8108

Pharmacokinetic: Time to Maximum plasma concentration of AZD6765 after Day 12 (MAD) dose AZD8108 Cohorts 5 \& 7, Cohort 6 did not reach day 12

Time frame: 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

Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD

Pharmacokinetic: Accumulation index for Area Under Concentration Curve (0 to 24 hour) MAD Cohorts 5 \& 7, cohort 6 did not reach day 12 \[accumulation index (Day 6 or 12 /Day1)\]

Time frame: Day 12 compared to Day 1