AZD8108 SAD/MAD in Healthy Volunteers

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AZD8108
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD8108<br>Subjects will participate in 1 of 7 groups and receive single or multiple doses of AZD8108 or matching placebo. In each group 6 subjects will receive AZD8108 | Drug: AZD8108<br>* Drug: AZD8108 Single or Multiple doses administered orally as a solution.<br>|
| Placebo Comparator: Placebo to match AZD8108<br>Subjects will participate in 1 of 7 groups and receive single or multiple doses of AZD8108 or matching placebo. In each group 2 subjects will receive matching placebo | Drug: Placebo<br>* Placebo to match AZD8108 Single or Multiple doses of matching placebo administered orally as a solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 
| Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 6 Dose of AZD8108 | Pharmacokinetic : Maximum concentration of AZD6765 after MAD Day 6 dose of AZD8108, Cohorts 5 & 7, Cohort 6 did not reach Day 6 | Pre-dose, 5,15.30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose | 
| Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 12 Dose of AZD8108 | Pharmacokinetic : Maximum concentration of AZD6765 after MAD Day 12 dose of AZD8108, Cohorts 5 & 7, Cohort 6 did not reach Day 12 | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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) | 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 | 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 | 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)] | Day 12 compared to Day 1 |