Study to Asses Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of AZD0328 in Patients With Schizophrenia

A Phase IIa, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Oral Multiple Ascending Doses of AZD0328 in Patients With Schizophrenia

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00669903

Enrollment

100

Registered

2008-05-01

Start date

2008-04-30

Completion date

2008-11-30

Last updated

2010-08-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia

Brief summary

This study is to assess the pharmacodynamics, pharmacokinetics, safety and tolerability of multiple ascending doses of AZD0328 in patients with schizophrenia

Interventions

DRUGAZD0328

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of schizophrenia according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) * Low level of Extra-pyramidal symptoms * No clinically significant findings on physical examination

Exclusion criteria

* Diagnosis of schizoaffective or schizophreniform disorders * Any significant psychiatric or neurological disease other than schizophrenia

Design outcomes

Primary

Measure	Time frame	Description
CogState Groton Maze Learning Task (GMLT) and One Card Learning Task (OCLT) Standardized Composite Score at Day 14	Baseline and Day 14	The GMLT and OCLT standardized change composite score will be calculated as the mean of the GMLT and OCLT standardized change from baseline scores. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate. Scale range from negative infinity (worst value) to positive infinity (best value).

Secondary

Measure	Time frame	Description
CogState Groton Maze Learning Task (GMLT) Standardized Change Score at Day 14	Baseline and Day 14	GMLT score is defined as the -log10 transform of the sum of the number of errors made during GMLT trials. Mean GMLT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The GMLT standardized change score was calculated as the change from baseline in the mean GMLT score divided by the within subject standard deviation. Scale range from negative infinity (worst value) to positive infinity (best value).
CogState One Card Learning Task (OCLT) Standardized Change Score at Day 14	Baseline and Day 14	OCLT score is defined as the arcsine transform of the proportion of correct responses during OCLT trials. Mean OCLT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The OCLT standardized change score was calculated as the change from baseline in the mean OCLT score divided by the within-subject standard deviation. Scale range from negative infinity (worst value) to positive infinity (best value).
CogState Detection Task (DT) Standardized Change Score at Day 14	Baseline and Day 14	DT score is defined as -1 times the mean of log10 transformed reaction times for all correct responses. Mean DT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The DT standardized change score will be calculated as the change from baseline in the mean DT score divided by the within-subject standard deviation. Score range from negative infinity (worst value) to positive infinity (best value).
CogState Identification Task (IT) Standardized Change Score at Day 14	Baseline and Day 14	IT score defined as 1 times the mean of log10 transformed reaction times for all correct responses. Mean IT score calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The IT standardized change score will be calculated as the change from baseline in the mean IT score divided by the within-subject standard dev. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate
CogState Groton Maze Recall Task (GMRT) Standardized Change Score at Day 14	Baseline and Day 14	GMRT score defined as the -log10 transform of the sum of the number of errors made during GMRT trials. Mean GMRT score calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The GMRT standardized change score was calculated as change from baseline in mean GMRT score divided by the within subject standard deviation. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, assessment day-by-treatment interaction as fixed factors, center as random factor, and baseline score as a covariate

Countries

United States

Participant flow

Recruitment details

A total of two US centers were inititated with first patient enrolled on 2 April 2008 and last patient completed on 4 November 2008. A total of 158 patients were enrolled with 100 patients allocated to randomized treatment.

Pre-assignment details

Patients were to receive a stable dose of an antipsychotic for the 4 weeks prior to randomization, have stable psychotic symptoms without a hospitalization for the 8 weeks prior to randomization, and were to be smoking an average of \>=10 cigarettes per day. Enrolled patients who no longer met entry criteria at randomization were not randomized.

Participants by arm

Arm	Count
AZD0328 Low Dose Group AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)	23
AZD0328 Optimal Dose Group AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)	37
AZD0328 High Dose Group AZD0328 High dose group (0.075 to 0.675 mg oral solution)	18
Placebo Placebo	22
Total	100

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	1	3	1
Overall Study	Lost to Follow-up	1	1	0	1
Overall Study	Protocol Violation	0	1	0	0
Overall Study	Withdrawal by Subject	0	2	2	2

Baseline characteristics

Characteristic	AZD0328 Low Dose Group	AZD0328 Optimal Dose Group	AZD0328 High Dose Group	Placebo	Total
Age Continuous	38.5 Years STANDARD_DEVIATION 11.2	41.7 Years STANDARD_DEVIATION 9.2	38.3 Years STANDARD_DEVIATION 9.8	40.0 Years STANDARD_DEVIATION 9.8	40.0 Years STANDARD_DEVIATION 9.9
Baseline Positive and Negative Syndrome Scale (PANSS) total score	67.9 Points of PANSS score STANDARD_DEVIATION 10.3	71.8 Points of PANSS score STANDARD_DEVIATION 12	72.1 Points of PANSS score STANDARD_DEVIATION 12.2	69.5 Points of PANSS score STANDARD_DEVIATION 13.2	70.4 Points of PANSS score STANDARD_DEVIATION 11.9
Race/Ethnicity, Customized Black	18 Participants	33 Participants	17 Participants	18 Participants	86 Participants
Race/Ethnicity, Customized Caucasian	4 Participants	3 Participants	1 Participants	2 Participants	10 Participants
Race/Ethnicity, Customized Other	1 Participants	1 Participants	0 Participants	2 Participants	4 Participants
Sex: Female, Male Female	1 Participants	4 Participants	3 Participants	2 Participants	10 Participants
Sex: Female, Male Male	22 Participants	33 Participants	15 Participants	20 Participants	90 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	17 / 23	22 / 37	11 / 18	11 / 22
serious Total, serious adverse events	0 / 23	0 / 37	0 / 18	1 / 22

Outcome results

Primary

CogState Groton Maze Learning Task (GMLT) and One Card Learning Task (OCLT) Standardized Composite Score at Day 14

The GMLT and OCLT standardized change composite score will be calculated as the mean of the GMLT and OCLT standardized change from baseline scores. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate. Scale range from negative infinity (worst value) to positive infinity (best value).