AZD8108 SAD/MAD in Healthy Volunteers
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02248818
Collaborator
(none)
258
1
2
10
25.8
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Study Type:
Interventional
Actual Enrollment
:
258 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
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 Start Date
:
Nov 1, 2014
Actual Primary Completion Date
:
Sep 1, 2015
Actual Study Completion Date
:
Sep 1, 2015
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Secondary Outcome Measures
- 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
- 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: 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)]
Other Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinilabs, Inc. | New York | New York | United States | 10019 |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Mina Pastagia, MD, MS, Clinilabs, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02248818
Other Study ID Numbers:
- D5800C00001
First Posted:
Sep 25, 2014
Last Update Posted:
Apr 7, 2017
Last Verified:
Mar 1, 2017
Study Results
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 Detail | Protocol allowed for 258 subjects to be screened, only 155 subjects were screened before all cohorts for the study were filled and recruitment ended. |
| Arm/Group Title | AZD8108 20 mg SAD | AZD8108 60 mg SAD | AZD8108 95 mg SAD | Placebo SAD | AZD8108 50 mg | AZD8108 90 mg MAD (6) | AZD8108 90 mg MAD (7) | Placebo MAD | Screen |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 | Screen - no treatment |
| Period Title: Screening | |||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 155 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 48 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 107 |
| Period Title: Screening | |||||||||
| STARTED | 6 | 6 | 6 | 6 | 6 | 8 | 6 | 4 | 0 |
| COMPLETED | 6 | 6 | 6 | 6 | 6 | 0 | 6 | 4 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 8 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8108 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 6 | 8 | 6 | 4 | 48 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [Years] |
36.0
(10.81)
|
36.3
(12.55)
|
38.7
(10.53)
|
38.0
(10.53)
|
36.7
(7.89)
|
35.4
(10.31)
|
31.2
(2.64)
|
39.3
(9.22)
|
36.0
(9.62)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
2
33.3%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
6.3%
|
| Male |
4
66.7%
|
6
100%
|
6
100%
|
5
83.3%
|
6
100%
|
8
100%
|
6
100%
|
4
100%
|
45
93.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||
| Hispanic or Latino |
2
33.3%
|
0
0%
|
1
16.7%
|
2
33.3%
|
2
33.3%
|
5
62.5%
|
0
0%
|
1
25%
|
13
27.1%
|
| Not Hispanic or Latino |
4
66.7%
|
6
100%
|
5
83.3%
|
4
66.7%
|
4
66.7%
|
3
37.5%
|
5
83.3%
|
2
50%
|
33
68.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
25%
|
2
4.2%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
12.5%
|
0
0%
|
0
0%
|
2
4.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
33.3%
|
4
66.7%
|
3
50%
|
3
50%
|
2
33.3%
|
2
25%
|
3
50%
|
2
50%
|
21
43.8%
|
| White |
2
33.3%
|
2
33.3%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
3
37.5%
|
3
50%
|
1
25%
|
15
31.3%
|
| More than one race |
2
33.3%
|
0
0%
|
1
16.7%
|
2
33.3%
|
2
33.3%
|
2
25%
|
0
0%
|
1
25%
|
10
20.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 8 | 6 | 4 |
| Number [Participants] |
2
33.3%
|
3
50%
|
0
0%
|
0
0%
|
4
66.7%
|
3
37.5%
|
0
0%
|
0
0%
|
| Title | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (those dosed with AZD8108) |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 6 | 6 | 6 | 0 | 6 | 8 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [hours*ng/mL] |
726
(22.4)
|
2651
(17.1)
|
4533
(11.3)
|
2160
(37.8)
|
4318
(13.2)
|
4597
(21.8)
|
| Title | Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hour), AZD6765 MAD Day 6 Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (those dosed with AZD8108) |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [hours*ng/mL] |
2061
(34.7)
|
4408
(26.3)
|
| Title | Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 MAD Day 12 Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (those dosed with AZD8108) |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [hours*ng/mL] |
2837
(47.6)
|
6733
(30.2)
|
| Title | Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hours), AZD6765 After DAY 12 Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (those dosed with AZD8108) |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [hours*ng/mL] |
2191
(38.1)
|
4670
(20.7)
|
| Title | Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (those dosed with AZD8108) |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 6 | 6 | 6 | 0 | 6 | 8 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
50.1
(22.4)
|
148
(19.3)
|
264
(17.8)
|
146
(27.5)
|
287
(22.7)
|
236
(10.6)
|
| Title | Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 6 Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (those dosed with AZD8108) MAD cohorts 5 & 7 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
176
(23.9)
|
330
(18.7)
|
| Title | Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 12 Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (those dosed with AZD8108) MAD cohorts 5 & 7 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
197
(30.4)
|
337
(11.3)
|
| Title | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population (subjects dosed with AZD8108) |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 6 | 6 | 6 | 0 | 6 | 8 | 6 | 0 |
| Median (Full Range) [hours] |
1.75
|
2.00
|
2.50
|
1.25
|
1.28
|
2.55
|
| Title | Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (Cohorts 1-3) AZD8108 dosed |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 6 | 6 | 6 | 0 | 0 | 0 | 0 | 0 |
| Measure Participants with urine volume data | 5 | 6 | 5 | 0 | 0 | 0 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [Percent] |
48.8
(55.2)
|
33.8
(30.1)
|
38.8
(8.24)
|
| Title | Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (MAD) After Day 12 Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population (Cohorts 1-3) AZD8108 dosed |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [Percent] |
49.4
(28.1)
|
30.2
(35.5)
|
| Title | Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Day 12 (MAD) Dose of AZD8108 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population (subjects dosed with AZD8108) |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Median (Full Range) [hours] |
1.75
|
1.80
|
| Title | Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population, MAD Cohorts 5 & 7 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 0 |
| Day 6 |
1.30
(0.181)
|
1.37
(0.224)
|
||||||
| Day 12 |
1.39
(0.254)
|
1.44
(0.165)
|
| Title | EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 8 | 6 | 4 |
| 0.5 hours after dose |
-0.069
(0.3715)
|
-0.272
(0.2422)
|
-0.166
(0.1880)
|
.0141
(0.2358)
|
-0.343
(0.3348)
|
0.087
(0.3979)
|
-0.154
(0.2555)
|
0.128
(0.5069)
|
| 1 hour after dose |
0.101
(0.2638)
|
-0.238
(0.4504)
|
-0.140
(0.2520)
|
-0.003
(0.1467)
|
-0.109
(0.5843)
|
0.092
(0.3466)
|
-0.063
(0.2291)
|
-0.121
(0.2005)
|
| 1.5 hours after dose |
-0.113
(0.2616)
|
-0.161
(0.6017)
|
-0.069
(0.2095)
|
0.097
(0.3402)
|
0.211
(0.5514)
|
-0.052
(0.3888)
|
0.016
(0.3687)
|
0.313
(0.2701)
|
| 2 hours after dose |
0.244
(0.2577)
|
-0.347
(0.3231)
|
-0.080
(0.2324)
|
-0.086
(0.2350)
|
-0.303
(0.4675)
|
-0.142
(0.2639)
|
-0.097
(0.2185)
|
0.019
(0.2661)
|
| 3 hours after dose |
0.214
(0.2120)
|
-0.254
(0.2461)
|
-0.108
(0.1569)
|
0.126
(0.1181)
|
-0.369
(0.4360)
|
0.058
(0.4186)
|
0.011
(0.3292)
|
0.247
(0.4936)
|
| 5 hours after dose |
-0.225
(0.1615)
|
-0.454
(0.2641)
|
-0.014
(0.1025)
|
0.138
(0.3071)
|
-0.514
(0.4117)
|
-0.073
(0.3506)
|
-0.25
(0.2971)
|
-0.151
(0.2954)
|
| 8 hours after dose |
0.222
(0.5150)
|
-0.263
(0.1219)
|
-0.086
(0.3075)
|
0.091
(0.4193)
|
-0.125
(0.4958)
|
-0.169
(0.3217)
|
-0.124
(0.3209)
|
0.034
(0.3623)
|
| Title | EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 4 |
| Pre-dose Day 6 dose |
-0.167
(0.3959)
|
0.080
(0.4827)
|
0.128
(0.3311)
|
|||||
| 0.5 hours after dose |
-0.514
(0.3729)
|
0.131
(0.3518)
|
0.384
(0.7434)
|
|||||
| 1 hour after dose |
-0.322
(0.6343)
|
0.063
(0.2129)
|
-0.123
(0.3713)
|
|||||
| 1.5 hours after dose |
-0.353
(0.2722)
|
0.109
(0.0729)
|
0.375
(0.5060)
|
|||||
| 2 hours after dose |
-0.460
(0.2219)
|
0.279
(0.5172)
|
0.223
(0.3813)
|
|||||
| 3 hours after dose |
-0.263
(0.4014)
|
0.016
(0.1550)
|
0.435
(0.3796)
|
|||||
| 5 hours after dose |
-0.350
(0.7782)
|
0.031
(0.2103)
|
-0.018
(0.6197)
|
|||||
| 8 hours after dose |
-0.454
(0.4568)
|
-0.028
(0.3062)
|
0.271
(0.3849)
|
| Title | EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 |
| Measure Participants | 0 | 0 | 0 | 0 | 6 | 0 | 6 | 4 |
| Pre dose Day 12 |
-0.075
(0.5040)
|
-0.065
(0.1789)
|
0.015
(0.1749)
|
|||||
| 0.5 hours post dose |
-0.309
(0.7025)
|
-0.134
(0.2459)
|
0.334
(0.3440)
|
|||||
| 1 hours post dose |
0.193
(1.4967)
|
-0.107
(0.1970)
|
0.253
(0.3448)
|
|||||
| 1.5 hours post dose |
0.073
(0.9299)
|
-0.062
(0.1783)
|
0.373
(0.3358)
|
|||||
| 2 hours post dose |
-0.207
(0.6381)
|
-0.087
(0.3025)
|
-0.046
(0.2830)
|
|||||
| 3 hours post dose |
-0.119
(0.6208)
|
-0.024
(0.2590)
|
0.234
(0.3109)
|
|||||
| 5 hours post dose |
-0.506
(0.4329)
|
0.040
(0.1775)
|
0.090
(0.4258)
|
|||||
| 8 hours post dose |
0.022
(1.0703)
|
-0.048
(0.0975)
|
0.178
(0.2510)
|
Adverse Events
| Time Frame | SAD cohorts 2 weeks, MAD cohorts up to 1 month | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | From Day -1 (entry into unit) until 14 days after last dose (15 days for SAD cohorts and up to 29 days for MAD cohorts) note Mad Cohort 6, stopped due to randomisation error in pharmacy had 15 days of follow up for adverse events. | |||||||||||||||
| Arm/Group Title | 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 | ||||||||
| Arm/Group Description | AZD8108 20 mg SAD, Cohort 1 | AZD8106 60 mg SAD, Cohort 2 | AZD8108 95 mg SAD, Cohort 3 | Placebo SAD, pooled across Cohorts 1 - 3 | AZD8108 50 mg MAD, Cohort 5 | AZD8108 90 mg MAD, Cohort 6 | AZD8108 90 mg MAD, Cohort 7 | Placebo MAD, pooled across Cohorts 5 & 7 | ||||||||
All Cause Mortality |
||||||||||||||||
| 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 | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| 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 | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | 0/6 (0%) | 0/4 (0%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| 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 | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 4/6 (66.7%) | 4/6 (66.7%) | 3/6 (50%) | 3/6 (50%) | 1/8 (12.5%) | 4/6 (66.7%) | 3/4 (75%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Leukopenia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| Palpitations | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Dyspepsia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Nausea | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| General disorders | ||||||||||||||||
| Chest Pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Infections and infestations | ||||||||||||||||
| Nasopharyngitis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Rash pustular | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Muscle Twitching | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Nervous system disorders | ||||||||||||||||
| Dysguesia | 6/6 (100%) | 6 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Nystagmus | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 1/6 (16.7%) | 1 | 2/4 (50%) | 2 |
| Dizziness | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Headache | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Sensory disturbance | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Psychiatric disorders | ||||||||||||||||
| Euphoric mood | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Halucination, visual | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Irritability | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Dysphoria | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Initial insomnia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Nightmare | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Nasal congestion | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Dermatitis acneiform | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
Limitations/Caveats
Conversion of AZD8108 to active moiety AZD6567 was rapid, concentrations of AZD8108 were almost all below the level of quantification, no PK parameters were calculable for AZD8108 concentrations.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Joel Posner MD |
|---|---|
| Organization | AstraZeneca LP |
| Phone | |
| ClinicalTrialTransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02248818
Other Study ID Numbers:
- D5800C00001
First Posted:
Sep 25, 2014
Last Update Posted:
Apr 7, 2017
Last Verified:
Mar 1, 2017