AZD8108 SAD/MAD in Healthy Volunteers (AZD8108)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: AZD8108; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10019
      • Clinilabs, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD8108; 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; Drug: AZD8108 Single or Multiple doses administered orally as a solution.
Placebo Comparator: Placebo to match AZD8108; 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; Placebo to match AZD8108 Single or Multiple doses of matching placebo administered orally as a solution

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction	EEG parameter (DAY 1) - Gamma - Change from baseline in Total Area of the Brain (eyes closed) - to identify a dose related change in EEG gamma bands to assess target engagement, a consistent change in either direction relative to placebo would be of interest	8 hours after dose
EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction	EEG parameter (DAY 6) - Gamma - Change from baseline in Total Area of the Brain (eyes closed) Cohort 5 & 7, Cohort 6 did not reach Day 6; to identify a dose related change in EEG gamma bands to assess target engagement, a consistent change in either direction compared to placebo was of interest	8 hours after dose
EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction	EEG parameter (DAY 12) - Gamma - Change from baseline in Total Area of the Brain (eyes closed) Cohort 5 & 7 , Cohort 6 did not reach Day 12; to identify a dose related change in EEG gamma bands to assess target engagement, a consistent change in either direction compared to placebo would be of interest	8 hours after dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Mina Pastagia, MD, MS, Clinilabs, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 24, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: D5800C00001