Trial Outcomes & Findings for Phase 2 Trial of a Nicotinic Agonist in Schizophrenia (NCT NCT00100165)

Last Updated: 2020-01-29

Results Overview

The measurement of neurocognitive performance on 6 domains, speed of processing, attention/vigilance, working memory, verbal learning, visual learning and reasoning/problem solving. Each domain is compared to a normative sample of schizophrenia subjects and the performance is determined and compared by a T-Test to the subjects baseline performance to determine the effect of drug or placebo. The scale is the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia Neurocognitive Consensus Combined Battery, range 0-100. A higher score indicates better performance.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

1 month

Results posted on

2020-01-29

Participant Flow

Thirty-four subjects were screened. Two were excluded because of abnormal laboratory values and one was excluded for a recent hospitalization. Thirty-one subjects were enrolled at two sites: The University of Colorado, Denver/Denver VA Medical Center (25 subjects) and The Maryland Psychiatric Research Center 6 subjects.

Subjects were administered 1 week of placebo to assess their ability to comply with BID dosing prior to administration of drug or placebo. There was a 1 week washout period between arms.

Participant milestones

Participant milestones
Measure	Placebo, Then DMXB-A 75, Then DMXB-A 150 Placebo then 3-(2,4-dimethoxybenzylidene) anabaseine 75 mg then 3-(2,4-dimethoxybenzylidene) anabaseine 150 mg	DMXB-A 75, Then DMXB-A 150, Then Placebo 3-(2,4-dimethoxybenzylidene) anabaseine 75 mg,then 3-(2,4-dimethoxybenzylidene) anabaseine 150 mg, then placebo	DMXB-A 150 mg, Then Placebo, Then DMXB-A 75 3-(2,4-dimethoxybenzylidene) anabaseine 150 mg, then placebo, then 3-(2,4-dimethoxybenzylidene) anabaseine 75 mg
Baseline STARTED	10	10	9
Baseline COMPLETED	10	10	9
Baseline NOT COMPLETED	0	0	0
First Intervention (4 Weeks) STARTED	10	10	9
First Intervention (4 Weeks) COMPLETED	10	10	9
First Intervention (4 Weeks) NOT COMPLETED	0	0	0
Washout (1 Week) STARTED	10	10	9
Washout (1 Week) COMPLETED	10	10	9
Washout (1 Week) NOT COMPLETED	0	0	0
Second Intervention (4 Weeks) STARTED	10	10	9
Second Intervention (4 Weeks) COMPLETED	10	10	9
Second Intervention (4 Weeks) NOT COMPLETED	0	0	0
Third Intervention (4 Weeks) STARTED	10	10	9
Third Intervention (4 Weeks) COMPLETED	10	10	9
Third Intervention (4 Weeks) NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 2 Trial of a Nicotinic Agonist in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DMXB-A 75, Then DMXB- 150, Then Placebo n=10 Participants Overall number of baseline participants 10 Age, continuous	Placebo, Then DMXB-A 75, Then DMXB-A 150 n=10 Participants Overall number of baseline participants 10 Age , continuous	DMXB-A 150, Then Placebo, Then DMXB-A 75 n=9 Participants Overall number of baseline participants 9 Age, continuous	Total n=29 Participants Total of all reporting groups
Age, Continuous	42.1 years STANDARD_DEVIATION 10.3 • n=5 Participants	40.5 years STANDARD_DEVIATION 9.8 • n=7 Participants	43.2 years STANDARD_DEVIATION 10.4 • n=5 Participants	41.6 years STANDARD_DEVIATION 10.1 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	9 participants n=5 Participants	29 participants n=4 Participants

PRIMARY outcome

Timeframe: 1 month

Population: change from baseline in cognitive performance as measured by a t-test at 4 weeks after taking the drug or placebo

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Change in t-score from baseline performance on neurocognitive measures when taking placebo for 4 weeks	3-(2,4-dimethoxybenzylidene) Anabaseine 75 mg n=29 Participants Change in t-scores from baseline neurocognitive performance when taking 3-(2,4-dimethoxybenzylidene) anabaseine 75 mg p.o. BID for 4 weeks	3-(2,4-dimethoxybenzylidene) Anabaseine 150 mg n=29 Participants Change in t-scores from baseline neurocognitive performance when taking3-(2,4-dimethoxybenzylidene) anabaseine 150 mg p.o BID for 4 weeks
Neurocognitive Performance	4.5 t-score change from baseline Standard Deviation 7.3	6.1 t-score change from baseline Standard Deviation 9.4	7.6 t-score change from baseline Standard Deviation 10.6

SECONDARY outcome

Timeframe: 1 month

Population: change in the total scale score from baseline measure with administration of either drug or placebo

The Scale for the Assessment of Negative Symptoms measures the measure negative symptoms in schizophrenia by measuring the domains of anhedonia, alogia, avolition and anhedonia in schizophrenia on a scale from 1 to 20 that sums the global scores of all 4 domains, each of which are rated on a scale of 1-5. Higher scores indicate greater severity of negative symptoms

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Change in t-score from baseline performance on neurocognitive measures when taking placebo for 4 weeks	3-(2,4-dimethoxybenzylidene) Anabaseine 75 mg n=29 Participants Change in t-scores from baseline neurocognitive performance when taking 3-(2,4-dimethoxybenzylidene) anabaseine 75 mg p.o. BID for 4 weeks	3-(2,4-dimethoxybenzylidene) Anabaseine 150 mg n=29 Participants Change in t-scores from baseline neurocognitive performance when taking3-(2,4-dimethoxybenzylidene) anabaseine 150 mg p.o BID for 4 weeks
Scale for the Assessment of Negative Symptoms (SANS)	6.1 units on a scale change from baseline Standard Deviation 9.4	7.6 units on a scale change from baseline Standard Deviation 10.6	4.6 units on a scale change from baseline Standard Deviation 6.5

Adverse Events

DMXB-A 75 mg

Serious events: 29 serious events

Other events: 0 other events

Deaths: 0 deaths

DMXBA 150 mg

Serious events: 29 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 29 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Dr. Robert Freedman

University of Colorado, Denver

Phone: 303 724-4940

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	DMXB-A 75 mg n=29 participants at risk 3-(2,4 dimethoxybenzylidene) 75 mg p.o. BID for 4 weeks	DMXBA 150 mg n=29 participants at risk 3-(2,4 dimethoxybenzylidene) 150 mg p.o. BID for 4 weeks	Placebo n=29 participants at risk Placebo p.o. BID for 4 weeks
Skin and subcutaneous tissue disorders rash	20.0% 2/10 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Psychiatric disorders insomnia	17.2% 5/29 • Number of events 5 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Nervous system disorders sedation	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
General disorders malaise	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Nervous system disorders headache	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Nervous system disorders dizziness	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Nervous system disorders restlessness	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Psychiatric disorders nervousness	31.0% 9/29 • Number of events 9 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	17.2% 5/29 • Number of events 5 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Eye disorders visual changes	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Ear and labyrinth disorders tinnitus	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
General disorders dry mouth	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
General disorders drooling	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
General disorders change in taste	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
General disorders diaphoresis	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Musculoskeletal and connective tissue disorders back pain	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	17.2% 5/29 • Number of events 5 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Gastrointestinal disorders nausea	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Gastrointestinal disorders diarrhea	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Gastrointestinal disorders flatulence	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Gastrointestinal disorders abdominal pain	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Gastrointestinal disorders constipation	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Renal and urinary disorders enuresis	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	0.00% 0/29 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Musculoskeletal and connective tissue disorders limb pain	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	13.8% 4/29 • Number of events 4 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Nervous system disorders stiffness	17.2% 5/29 • Number of events 5 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Nervous system disorders tremor	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	17.2% 5/29 • Number of events 5 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Nervous system disorders parasthesias	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	10.3% 3/29 • Number of events 3 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	6.9% 2/29 • Number of events 2 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Psychiatric disorders hallucinations	31.0% 9/29 • Number of events 9 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	31.0% 9/29 • Number of events 9 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	27.6% 8/29 • Number of events 8 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention
Psychiatric disorders delusions	31.0% 9/29 • Number of events 9 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	17.2% 5/29 • Number of events 5 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention	20.7% 6/29 • Number of events 6 • Four weeks for each intervention Safety population included all participants who received at least one dose of intervention