Healthy Volunteers
Conditions
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
Interventions
DRUGAZD8108
Drug: AZD8108 Single or Multiple doses administered orally as a solution.
DRUGPlacebo
Placebo to match AZD8108 Single or Multiple doses of matching placebo administered orally as a solution
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 12 Dose of AZD8108 | 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 : Maximum concentration of AZD6765 after MAD Day 12 dose of AZD8108, Cohorts 5 & 7, Cohort 6 did not reach Day 12 |
| Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | Day -1 to 7 days after last dose | Safety Laboratory - Thyroid Stimulating Hormone participants with laboratory value above the upper limit of normal |
| Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st 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 infinity), AZD6765 after single/first dose of AZD8108 |
| Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hour), AZD6765 MAD Day 6 Dose of AZD8108 | 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 24 hour), AZD6765 MAD Day 6 dose of AZD8108 Cohort 5 & 7, Cohort 6 did not reach Day 6 |
| Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 MAD Day 12 Dose of AZD8108 | 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 infinity), AZD6765 MAD Day 12 dose of AZD8108 Cohort 5 & 7, Cohort 6 did not reach Day 12 |
| Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hours), AZD6765 After DAY 12 Dose of AZD8108 | Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16, and 24 hours after dose | 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 |
| Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st 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 single/first dose of AZD8108 |
| Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 6 Dose of AZD8108 | 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 6 dose of AZD8108, Cohorts 5 & 7, Cohort 6 did not reach Day 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD | Day 12 compared to Day 1 | Pharmacokinetic: Accumulation index for Area Under Concentration Curve (0 to 24 hour) MAD Cohorts 5 & 7, cohort 6 did not reach day 12 \[accumulation index (Day 6 or 12 /Day1)\] |
| Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108 | 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 (SAD) after single dose of AZD8108 (Cohorts 1 - 3) |
| Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (MAD) After Day 12 Dose of AZD8108 | Collection 0-6, 0-12, 12-24, 24-48, 48-72 hr after Day 12 dose | 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 |
| Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Day 12 (MAD) Dose of AZD8108 | 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: Time to Maximum plasma concentration of AZD6765 after Day 12 (MAD) dose AZD8108 Cohorts 5 & 7, Cohort 6 did not reach day 12 |
| Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of 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: Time to Maximum plasma concentration of AZD6765 after single (SAD) / first (MAD) dose AZD8108 |
Other
| Measure | Time frame | Description |
|---|---|---|
| EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | 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 |
| EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 8 hours after dose | 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 |
| EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | 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 |
Countries
United States
Participant flow
Recruitment details
Healthy Adult volunteer study, Part 1: SAD: single ascending dose cohorts, followed by Part 2: MAD: multiple ascending dose cohorts. Plan was for each cohort to have 8 subjects, 2 placebo dosed and 6 AZD8108 dosed.
Pre-assignment details
Protocol allowed for 258 subjects to be screened, only 155 subjects were screened before all cohorts for the study were filled and recruitment ended.
Participants by arm
| Arm | Count |
|---|---|
| AZD8108 20 mg - SAD AZD8108 20 mg SAD, Cohort 1 | 6 |
| AZD8108 60 mg - SAD AZD8108 60 mg SAD, Cohort 2 | 6 |
| AZD8108 95 mg - SAD AZD8108 95 mg SAD, Cohort 3 | 6 |
| Placebo SAD Placebo SAD, pooled across Cohorts 1 - 3 | 6 |
| AZD8108 50 mg MAD AZD8108 50 mg MAD, Cohort 5 | 6 |
| AZD8108 90 mg MAD (6) AZD8108 90 mg MAD, Cohort 6 | 8 |
| AZD8108 90 mg MAD (7) AZD8108 90 mg MAD, Cohort 7 | 6 |
| Placebo MAD Placebo MAD, pooled across Cohorts 5 & 7 | 4 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Randomised Study | Administrative - randomization error | 0 | 0 | 0 | 0 | 0 | 8 | 0 | 0 | 0 |
| Screening | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 |
| Screening | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 73 |
| Screening | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 |
| Screening | Study fully enrolled | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 |
| Screening | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
Baseline characteristics
| Characteristic | AZD8108 20 mg - SAD | AZD8108 60 mg - SAD | AZD8108 95 mg - SAD | Placebo SAD | AZD8108 50 mg MAD | AZD8108 90 mg MAD (6) | AZD8108 90 mg MAD (7) | Placebo MAD | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 36.0 Years STANDARD_DEVIATION 10.81 | 36.3 Years STANDARD_DEVIATION 12.55 | 38.7 Years STANDARD_DEVIATION 10.53 | 38.0 Years STANDARD_DEVIATION 10.53 | 36.7 Years STANDARD_DEVIATION 7.89 | 35.4 Years STANDARD_DEVIATION 10.31 | 31.2 Years STANDARD_DEVIATION 2.64 | 39.3 Years STANDARD_DEVIATION 9.22 | 36.0 Years STANDARD_DEVIATION 9.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants | 0 Participants | 1 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 5 Participants | 2 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 15 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 8 Participants | 6 Participants | 4 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 4 / 6 | 4 / 6 | 3 / 6 | 3 / 6 | 1 / 8 | 4 / 6 | 3 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 4 |
Outcome results
Primary
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
Population: Pharmacokinetic Population (those dosed with AZD8108)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hour), AZD6765 MAD Day 6 Dose of AZD8108 | 2061 hours*ng/mL | Geometric Coefficient of Variation 34.7 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hour), AZD6765 MAD Day 6 Dose of AZD8108 | 4408 hours*ng/mL | Geometric Coefficient of Variation 26.3 |
Primary
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
Population: Pharmacokinetic Population (those dosed with AZD8108)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hours), AZD6765 After DAY 12 Dose of AZD8108 | 2191 hours*ng/mL | Geometric Coefficient of Variation 38.1 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hours), AZD6765 After DAY 12 Dose of AZD8108 | 4670 hours*ng/mL | Geometric Coefficient of Variation 20.7 |
Primary
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
Population: Pharmacokinetic Population (those dosed with AZD8108)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 20 mg SAD | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108 | 726 hours*ng/mL | Geometric Coefficient of Variation 22.4 |
| AZD8108 60 mg SAD | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108 | 2651 hours*ng/mL | Geometric Coefficient of Variation 17.1 |
| AZD8108 95 mg SAD | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108 | 4533 hours*ng/mL | Geometric Coefficient of Variation 11.3 |
| AZD8108 50 mg MAD | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108 | 2160 hours*ng/mL | Geometric Coefficient of Variation 37.8 |
| AZD8108 90 mg MAD (6) | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108 | 4318 hours*ng/mL | Geometric Coefficient of Variation 13.2 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108 | 4597 hours*ng/mL | Geometric Coefficient of Variation 21.8 |
Primary
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
Population: Pharmacokinetic Population (those dosed with AZD8108)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 MAD Day 12 Dose of AZD8108 | 2837 hours*ng/mL | Geometric Coefficient of Variation 47.6 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 MAD Day 12 Dose of AZD8108 | 6733 hours*ng/mL | Geometric Coefficient of Variation 30.2 |
Primary
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
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
Population: Pharmacokinetic Population (those dosed with AZD8108) MAD cohorts 5 \& 7
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 12 Dose of AZD8108 | 197 ng/mL | Geometric Coefficient of Variation 30.4 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 12 Dose of AZD8108 | 337 ng/mL | Geometric Coefficient of Variation 11.3 |
Primary
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
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
Population: Pharmacokinetic Population (those dosed with AZD8108) MAD cohorts 5 \& 7
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 6 Dose of AZD8108 | 176 ng/mL | Geometric Coefficient of Variation 23.9 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 6 Dose of AZD8108 | 330 ng/mL | Geometric Coefficient of Variation 18.7 |
Primary
Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108
Pharmacokinetic : Maximum concentration of AZD6765 after single/first dose of AZD8108
Time frame: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,25,48,972 SAD only)hr after Day 1 dose
Population: Pharmacokinetic Population (those dosed with AZD8108)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 20 mg SAD | Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108 | 50.1 ng/mL | Geometric Coefficient of Variation 22.4 |
| AZD8108 60 mg SAD | Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108 | 148 ng/mL | Geometric Coefficient of Variation 19.3 |
| AZD8108 95 mg SAD | Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108 | 264 ng/mL | Geometric Coefficient of Variation 17.8 |
| AZD8108 50 mg MAD | Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108 | 146 ng/mL | Geometric Coefficient of Variation 27.5 |
| AZD8108 90 mg MAD (6) | Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108 | 287 ng/mL | Geometric Coefficient of Variation 22.7 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108 | 236 ng/mL | Geometric Coefficient of Variation 10.6 |
Primary
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
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD8108 20 mg SAD | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 2 Participants |
| AZD8108 60 mg SAD | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 3 Participants |
| AZD8108 95 mg SAD | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 0 Participants |
| Placebo SAD | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 0 Participants |
| AZD8108 50 mg MAD | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 4 Participants |
| AZD8108 90 mg MAD (6) | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 3 Participants |
| AZD8108 90 mg MAD (7) | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 0 Participants |
| Placebo MAD | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal | 0 Participants |
Secondary
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
Population: Pharmacokinetic population, MAD Cohorts 5 \& 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD | Day 6 | 1.30 ratio | Standard Deviation 0.181 |
| AZD8108 50 mg MAD | Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD | Day 12 | 1.39 ratio | Standard Deviation 0.254 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD | Day 6 | 1.37 ratio | Standard Deviation 0.224 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD | Day 12 | 1.44 ratio | Standard Deviation 0.165 |
Secondary
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
Population: Pharmacokinetic Population (Cohorts 1-3) AZD8108 dosed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (MAD) After Day 12 Dose of AZD8108 | 49.4 Percent | Geometric Coefficient of Variation 28.1 |
| AZD8108 90 mg MAD (7) | Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (MAD) After Day 12 Dose of AZD8108 | 30.2 Percent | Geometric Coefficient of Variation 35.5 |
Secondary
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
Population: Pharmacokinetic Population (Cohorts 1-3) AZD8108 dosed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8108 20 mg SAD | Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108 | 48.8 Percent | Geometric Coefficient of Variation 55.2 |
| AZD8108 60 mg SAD | Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108 | 33.8 Percent | Geometric Coefficient of Variation 30.1 |
| AZD8108 95 mg SAD | Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108 | 38.8 Percent | Geometric Coefficient of Variation 8.24 |
Secondary
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
Population: Pharmacokinetic population (subjects dosed with AZD8108)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD8108 50 mg MAD | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Day 12 (MAD) Dose of AZD8108 | 1.75 hours |
| AZD8108 90 mg MAD (7) | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Day 12 (MAD) Dose of AZD8108 | 1.80 hours |
Secondary
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
Population: Pharmacokinetic population (subjects dosed with AZD8108)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD8108 20 mg SAD | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108 | 1.75 hours |
| AZD8108 60 mg SAD | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108 | 2.00 hours |
| AZD8108 95 mg SAD | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108 | 2.50 hours |
| AZD8108 50 mg MAD | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108 | 1.25 hours |
| AZD8108 90 mg MAD (6) | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108 | 1.28 hours |
| AZD8108 90 mg MAD (7) | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108 | 2.55 hours |
Other Pre-specified
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
Time frame: 8 hours after dose
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | Pre dose Day 12 | -0.075 uV2 | Standard Deviation 0.504 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 0.5 hours post dose | -0.309 uV2 | Standard Deviation 0.7025 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 1 hours post dose | 0.193 uV2 | Standard Deviation 1.4967 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 1.5 hours post dose | 0.073 uV2 | Standard Deviation 0.9299 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 2 hours post dose | -0.207 uV2 | Standard Deviation 0.6381 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 3 hours post dose | -0.119 uV2 | Standard Deviation 0.6208 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 5 hours post dose | -0.506 uV2 | Standard Deviation 0.4329 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 8 hours post dose | 0.022 uV2 | Standard Deviation 1.0703 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 1 hours post dose | -0.107 uV2 | Standard Deviation 0.197 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 5 hours post dose | 0.040 uV2 | Standard Deviation 0.1775 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 1.5 hours post dose | -0.062 uV2 | Standard Deviation 0.1783 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 2 hours post dose | -0.087 uV2 | Standard Deviation 0.3025 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 3 hours post dose | -0.024 uV2 | Standard Deviation 0.259 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | Pre dose Day 12 | -0.065 uV2 | Standard Deviation 0.1789 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 0.5 hours post dose | -0.134 uV2 | Standard Deviation 0.2459 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 8 hours post dose | -0.048 uV2 | Standard Deviation 0.0975 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 1 hours post dose | 0.253 uV2 | Standard Deviation 0.3448 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 0.5 hours post dose | 0.334 uV2 | Standard Deviation 0.344 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | Pre dose Day 12 | 0.015 uV2 | Standard Deviation 0.1749 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 1.5 hours post dose | 0.373 uV2 | Standard Deviation 0.3358 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 5 hours post dose | 0.090 uV2 | Standard Deviation 0.4258 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 3 hours post dose | 0.234 uV2 | Standard Deviation 0.3109 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 2 hours post dose | -0.046 uV2 | Standard Deviation 0.283 |
| Placebo MAD | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction | 8 hours post dose | 0.178 uV2 | Standard Deviation 0.251 |
Other Pre-specified
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
Time frame: 8 hours after dose
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD8108 20 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | 0.214 uV2 | Standard Deviation 0.212 |
| AZD8108 20 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.225 uV2 | Standard Deviation 0.1615 |
| AZD8108 20 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | -0.113 uV2 | Standard Deviation 0.2616 |
| AZD8108 20 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | -0.069 uV2 | Standard Deviation 0.3715 |
| AZD8108 20 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | 0.101 uV2 | Standard Deviation 0.2638 |
| AZD8108 20 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | 0.244 uV2 | Standard Deviation 0.2577 |
| AZD8108 20 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | 0.222 uV2 | Standard Deviation 0.515 |
| AZD8108 60 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | -0.263 uV2 | Standard Deviation 0.1219 |
| AZD8108 60 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | -0.254 uV2 | Standard Deviation 0.2461 |
| AZD8108 60 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.238 uV2 | Standard Deviation 0.4504 |
| AZD8108 60 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | -0.161 uV2 | Standard Deviation 0.6017 |
| AZD8108 60 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | -0.347 uV2 | Standard Deviation 0.3231 |
| AZD8108 60 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | -0.272 uV2 | Standard Deviation 0.2422 |
| AZD8108 60 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.454 uV2 | Standard Deviation 0.2641 |
| AZD8108 95 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | -0.108 uV2 | Standard Deviation 0.1569 |
| AZD8108 95 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | -0.086 uV2 | Standard Deviation 0.3075 |
| AZD8108 95 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | -0.080 uV2 | Standard Deviation 0.2324 |
| AZD8108 95 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.140 uV2 | Standard Deviation 0.252 |
| AZD8108 95 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | -0.166 uV2 | Standard Deviation 0.188 |
| AZD8108 95 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.014 uV2 | Standard Deviation 0.1025 |
| AZD8108 95 mg SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | -0.069 uV2 | Standard Deviation 0.2095 |
| Placebo SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | -0.086 uV2 | Standard Deviation 0.235 |
| Placebo SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | 0.091 uV2 | Standard Deviation 0.4193 |
| Placebo SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.003 uV2 | Standard Deviation 0.1467 |
| Placebo SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | 0.138 uV2 | Standard Deviation 0.3071 |
| Placebo SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | 0.097 uV2 | Standard Deviation 0.3402 |
| Placebo SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | .0141 uV2 | Standard Deviation 0.2358 |
| Placebo SAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | 0.126 uV2 | Standard Deviation 0.1181 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | -0.303 uV2 | Standard Deviation 0.4675 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | -0.343 uV2 | Standard Deviation 0.3348 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.109 uV2 | Standard Deviation 0.5843 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | 0.211 uV2 | Standard Deviation 0.5514 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | -0.369 uV2 | Standard Deviation 0.436 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.514 uV2 | Standard Deviation 0.4117 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | -0.125 uV2 | Standard Deviation 0.4958 |
| AZD8108 90 mg MAD (6) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | -0.142 uV2 | Standard Deviation 0.2639 |
| AZD8108 90 mg MAD (6) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | -0.169 uV2 | Standard Deviation 0.3217 |
| AZD8108 90 mg MAD (6) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | 0.058 uV2 | Standard Deviation 0.4186 |
| AZD8108 90 mg MAD (6) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | -0.052 uV2 | Standard Deviation 0.3888 |
| AZD8108 90 mg MAD (6) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.073 uV2 | Standard Deviation 0.3506 |
| AZD8108 90 mg MAD (6) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | 0.092 uV2 | Standard Deviation 0.3466 |
| AZD8108 90 mg MAD (6) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | 0.087 uV2 | Standard Deviation 0.3979 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.063 uV2 | Standard Deviation 0.2291 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | -0.154 uV2 | Standard Deviation 0.2555 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.25 uV2 | Standard Deviation 0.2971 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | 0.011 uV2 | Standard Deviation 0.3292 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | -0.124 uV2 | Standard Deviation 0.3209 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | 0.016 uV2 | Standard Deviation 0.3687 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | -0.097 uV2 | Standard Deviation 0.2185 |
| Placebo MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | 0.034 uV2 | Standard Deviation 0.3623 |
| Placebo MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | 0.019 uV2 | Standard Deviation 0.2661 |
| Placebo MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.151 uV2 | Standard Deviation 0.2954 |
| Placebo MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | 0.128 uV2 | Standard Deviation 0.5069 |
| Placebo MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | 0.313 uV2 | Standard Deviation 0.2701 |
| Placebo MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | 0.247 uV2 | Standard Deviation 0.4936 |
| Placebo MAD | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.121 uV2 | Standard Deviation 0.2005 |
Other Pre-specified
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
Time frame: 8 hours after dose
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | Pre-dose Day 6 dose | -0.167 uV2 | Standard Deviation 0.3959 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | -0.514 uV2 | Standard Deviation 0.3729 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.322 uV2 | Standard Deviation 0.6343 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | -0.353 uV2 | Standard Deviation 0.2722 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | -0.460 uV2 | Standard Deviation 0.2219 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | -0.263 uV2 | Standard Deviation 0.4014 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.350 uV2 | Standard Deviation 0.7782 |
| AZD8108 50 mg MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | -0.454 uV2 | Standard Deviation 0.4568 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | 0.063 uV2 | Standard Deviation 0.2129 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | 0.031 uV2 | Standard Deviation 0.2103 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | 0.109 uV2 | Standard Deviation 0.0729 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | 0.279 uV2 | Standard Deviation 0.5172 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | 0.016 uV2 | Standard Deviation 0.155 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | Pre-dose Day 6 dose | 0.080 uV2 | Standard Deviation 0.4827 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | 0.131 uV2 | Standard Deviation 0.3518 |
| AZD8108 90 mg MAD (7) | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | -0.028 uV2 | Standard Deviation 0.3062 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1 hour after dose | -0.123 uV2 | Standard Deviation 0.3713 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 0.5 hours after dose | 0.384 uV2 | Standard Deviation 0.7434 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | Pre-dose Day 6 dose | 0.128 uV2 | Standard Deviation 0.3311 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 1.5 hours after dose | 0.375 uV2 | Standard Deviation 0.506 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 5 hours after dose | -0.018 uV2 | Standard Deviation 0.6197 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 3 hours after dose | 0.435 uV2 | Standard Deviation 0.3796 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 2 hours after dose | 0.223 uV2 | Standard Deviation 0.3813 |
| Placebo MAD | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction | 8 hours after dose | 0.271 uV2 | Standard Deviation 0.3849 |