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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01714661




Registration number
NCT01714661
Ethics application status
Date submitted
19/10/2012
Date registered
26/10/2012
Date last updated
3/05/2016

Titles & IDs
Public title
Study of EVP-6124 (Alpha-7 nAChR) as an Adjunctive Pro-Cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy
Scientific title
A Randomized, Double-blind, Placebo-controlled, Parallel, 26-Week, Phase 3 Study of 2 Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist (EVP-6124) or Placebo as an Adjunctive Pro-cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy
Secondary ID [1] 0 0
2012-003208-10
Secondary ID [2] 0 0
EVP-6124-015
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 0 0
Impaired Cognition 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Schizophrenia
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EVP-6124
Treatment: Drugs - Placebo

Experimental: EVP-6124, low dose - low dose, Tablet, Once Daily, Day 1 through Day 182

Experimental: EVP-6124, high dose - high dose, Tablet, Once Daily, Day 1 through Day 182

Placebo Comparator: EVP-6124, Placebo - Placebo, Tablet, Once Daily, Day -14 through Day 182


Treatment: Drugs: EVP-6124
Arms 1, 2

Treatment: Drugs: Placebo
Arm 3
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) to Day 182
Timepoint [1] 0 0
Baseline to Day 182 or Early Termination
Primary outcome [2] 0 0
Change from Baseline in the Schizophrenia Cognition Rating Scale (SCoRs) to Day 182
Timepoint [2] 0 0
Baseline to Day 182 or Early Terminiation
Primary outcome [3] 0 0
Safety and Tolerability of EVP-6124 or Placebo in Subjects with Schizophrenia
Timepoint [3] 0 0
Screening (Day -42 to Day -15) to Day 182 or Early Terminiation
Secondary outcome [1] 0 0
Change from Baseline in the Positive and Negative Symptom Scale (PANSS) to Day 182
Timepoint [1] 0 0
Baseline to Day 182 or Early Termination
Secondary outcome [2] 0 0
Change from Baseline in the Clinical Global Impression-Severity (CGI-S) to Day 182
Timepoint [2] 0 0
Baseline to Day 182 or Early Termination
Secondary outcome [3] 0 0
Change from Baseline in the Clinical Global Impression Change Scale (CGI-C) to Day 182
Timepoint [3] 0 0
Baseline to Day 182 or Early Termination
Secondary outcome [4] 0 0
Change from Baseline in the EuroQOL-5D (EQ-5D) to Day 182
Timepoint [4] 0 0
Baseline to Day 182 or Early Termination

Eligibility
Key inclusion criteria
- Age 18 to 50 years of age, inclusive

- Signed informed consent, indicating that the subject understands the purpose of and
procedures required for the study, before the initiation of any study specific
procedures. Subjects who are unable to provide informed consent will not be included
in the study.

- Resides in a stable living situation, according to the investigator's judgment, and
must have an identified informant who should be consistent throughout the study. If
possible, the informant should accompany the subject or be available for in person
ratings at the screening, baseline (Day 1), and final study visits. In person
informant ratings on all relevant study visits are preferred whenever possible.
However, if the informant is not available for in person ratings, telephone interview
is acceptable. The informant must be available for a telephone interview throughout
the study at all visits. As long as both the informant visit and subject visit are
within the study visit windows, it is not necessary that they occur on the same day.
The informant must interact with the subject at least 2 times a week.

- Diagnosis of Schizophrenia of at least 3 years duration. This diagnosis can be
established utilizing the SCID-I, direct clinical assessments, family, informants, and
confirmation of diagnosis from clinical sources. These may include medical records,
confirmation of diagnosis by treating clinician through telephone contact, or written
confirmation from treating clinic. If the listed sources are not available, other
sources of diagnostic confirmation may also be acceptable after discussion with the
medical monitor.

- Treated with atypical antipsychotic drug (in any approved dosage form) other than
Clozapine at a stable dose for at least 8 weeks prior to screening and be clinically
stable; the subject must remain clinically stable (in the opinion of the principal
investigator) through randomization. The use of up to 2 atypical antipsychotic drugs
is permitted, as long as in the opinion of the investigator, the second medication is
not required to control treatment-resistant or intractable psychotic symptoms. No
subject will be washed off antipsychotic therapy to become eligible for this study.

- Schizophrenia clinical symptom burden severity defined by the following: a Brief
Psychiatric Rating Scale (BPRS) Conceptual Disorganization item score = 4; and a BPRS
Hallucinatory Behavior item score = 5, or an Unusual Thought Content item score = 5.
Either Hallucinatory Behavior or Unusual Thought Content, but not both, may have a
score of 6 (but not > 6).

- Simpson-Angus Scale (SAS) total score = 6

- Calgary Depression Scale for Schizophrenia (CDSS) total score = 10

- General health status acceptable for participation in a 26-week clinical study

- Fertile, sexually active subjects (men and women) must use an effective method of
contraception during the study

- Fluency (oral and written) in the language in which the standardized tests will be
administered

- The ability to refrain from using any tobacco or other nicotine-containing products
for at least 30 minutes before any cognitive testing
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Hospitalization within 12 weeks before screening or during the screening period, or
change of antipsychotic medication or dose within 8 weeks before screening or during
the screening period.

- Participation in another therapeutic (medication administration) clinical study within
the past 2 months.

- Psychiatric hospitalization or incarcerations due to breakthrough symptoms or acute
exacerbations for a period of 3 months before screening. Subjects with a recent
"social" hospitalization or incarceration may be entered into screening after
consultation with the medical monitor

- Likelihood, in the opinion of the investigator, that either the subject or informant
will be unable to complete a 26-week study

- Treatment with prohibited antipsychotic drug, and/or treatment with more than 2
permitted antipsychotic drugs. Treatment with a first-generation antipsychotic drug
(typical antipsychotic) is prohibited unless it is administered at a low dose after
discussion with the medical monitor

- Current treatment with any anticholinergic agent

- Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)
criteria met for alcohol abuse within the past 3 months or substance abuse (other than
nicotine) within the last 6 months before screening

- Significant suicide risk as defined by 1) suicidal ideation as endorsed on items 4 or
5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past year; 2)
suicidal behavior detected by the C-SSRS during the past 2 years, or 3) psychiatric
interview and examination

- Stroke within 6 months before screening, history of brain tumor, subdural hematoma, or
other clinically significant neurological condition, head trauma with loss of
consciousness within 12 months before screening

- Monoamine oxidase inhibitor antidepressants or tricyclic medications used in
antidepressant doses are excluded. Other antidepressant medications are allowed if the
subject has been treated with a stable dose for at least 3 months before screening

- Immunosuppressants, mood stabilizers, chronic use of a sedative hypnotic drug, chronic
intake of clinically significant doses of opioid containing analgesics or any current
methadone treatment all in the judgment of the investigator may be permitted depending
on the circumstance

- Use of Central Nervous System(CNS) stimulants

- Nicotine therapy (including patches), varenicline (Chantix), or similar therapeutic
agent within the last six months before screening

- Use of a benzodiazepine medication is allowed if the subject has not had a change in
medication or dose for at least 3 months. For subjects prescribed benzodiazepines,
short-acting benzodiazepines are to be used whenever possible. Use of longer-acting
benzodiazepines may be acceptable if prior authorization is obtained from the medical
monitor. When possible, benzodiazepines should not be administered within 3 hours
before cognitive testing. The use of more than one sedative-hypnotic medication is not
allowed.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2015
Sample size
Target
Accrual to date
Final
753
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
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United States of America
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Arizona
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California
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Florida
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Georgia
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Illinois
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Kansas
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Louisiana
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Minnesota
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Mississippi
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Missouri
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Nebraska
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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Texas
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Argentina
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Buenos Aires
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Argentina
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Caba
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Argentina
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Cordoba
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Argentina
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Mendoza
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Brazil
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SP
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Brazil
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Rio de Janeiro
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Brazil
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Sao Paulo
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Germany
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Achim
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Germany
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Berlin
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Germany
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Dusseldorf
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Germany
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Freiburg
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Germany
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Leipzig
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Germany
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Munchen
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Regebsburg
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Regensburg
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Germany
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Stralsund
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Germany
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Wiesbaden
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D.F
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Jalisco
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Neuvo Leon
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Bialystok
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Gdansk
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Lodz
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Lublin
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Torun
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Tuszyn
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Warszawa
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Russian Federation
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Arkangelsk region
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Russian Federation
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Moscow
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Russian Federation
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Saint-Petersburg
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Russian Federation
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Stavropol
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Serbia
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Belgrade
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Serbia
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Kragujevac
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Serbia
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Nis
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Serbia
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Novi Knezevac
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Castilla y Leon
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Spain
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Madrid
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Spain
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Pontevedra
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Ukraine
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Donetsk
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Ukraine
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Ivano-Frankivsk
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Ukraine
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Lugansk

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
FORUM Pharmaceuticals Inc
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Syneos Health
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
NeuroCog Trials, Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine if EVP-6124 (an alpha-7 nAChR agonist) enhances the
cognitive abilities of subjects with Schizophrenia who are also taking stable antipsychotic
therapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01714661
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Address 0 0
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Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01714661