Study of EVP-6124 (Alpha-7 nAChR) as an Adjunctive Pro-Cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy

NCT ID: NCT01716975

Last Updated: 2016-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 767 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-02-29

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.

Conditions

Schizophrenia; Impaired Cognition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

EVP-6124, Placebo

Placebo, Tablet, Once Daily, Day -14 through Day 182

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Arm 3

EVP-6124, low dose

low dose, Tablet, Once Daily, Day 1 through Day 182

Group Type: EXPERIMENTAL

EVP-6124

Intervention Type: DRUG

Arms 1, 2

EVP-6124, high dose

high dose, Tablet, Once Daily, Day 1 through Day 182

Group Type: EXPERIMENTAL

EVP-6124

Intervention Type: DRUG

Arms 1, 2

Interventions

EVP-6124

Arms 1, 2

Intervention Type: DRUG

Placebo

Arm 3

Intervention Type: DRUG

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Syneos Health

OTHER

Sponsor Role: collaborator

NeuroCog Trials, Inc.

INDUSTRY

Sponsor Role: collaborator

FORUM Pharmaceuticals Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Phoenixville, Arizona, United States

Little Rock, Arkansas, United States

Cerritos, California, United States

Chino, California, United States

Costa Mesa, California, United States

Garden Grove, California, United States

Glendale, California, United States

Norwalk, California, United States

Oakland, California, United States

Oakland Park, California, United States

Oceanside, California, United States

Riverside, California, United States

San Diego, California, United States

San Gabriel, California, United States

Santa Ana, California, United States

Sherman Oaks, California, United States

Washington D.C., District of Columbia, United States

Bradenton, Florida, United States

Miami, Florida, United States

Miami Springs, Florida, United States

North Miami, Florida, United States

Orlando, Florida, United States

Marietta, Georgia, United States

Smyrna, Georgia, United States

Chicago, Illinois, United States

Oak Brook, Illinois, United States

Oak Park, Illinois, United States

Wichita, Kansas, United States

Lake Charles, Louisiana, United States

Shreveport, Louisiana, United States

Rockville, Maryland, United States

Boston, Massachusetts, United States

Saint Charles, Missouri, United States

St Louis, Missouri, United States

Lincoln, Nebraska, United States

Princeton, New Jersey, United States

Jamaica, New York, United States

New York, New York, United States

Rochester, New York, United States

Charlotte, North Carolina, United States

Beachwood, Ohio, United States

Oklahoma City, Oklahoma, United States

Jenkintown, Pennsylvania, United States

Austin, Texas, United States

Dallas, Texas, United States

Salt Lake City, Utah, United States

Bellevue, Washington, United States

Richland, Washington, United States

Spokane, Washington, United States

Banfield, Buenos Aires, Argentina

Caba, Buenos Aires F.D., Argentina

Mendoza, Mendoza Province, Argentina

Rosario, Santa Fe Province, Argentina

Santiago del Estero, , Argentina

Adelaide, South Australia, Australia

Mount Claremont, Western Australia, Australia

Salvader, Estado de Bahia, Brazil

Belo Horizonte, Minas Gerais, Brazil

Curitiba, Paraná, Brazil

Medellín, Antioquia, Colombia

Barranquilla, Atlántico, Colombia

Pereira, Risaralda Department, Colombia

Bogota D.C., , Colombia

Florence, FL, Italy

Milan, MI, Italy

Ban, , Italy

Barl, , Italy

Catania, , Italy

Lucca, , Italy

Milan, , Italy

Pisa, , Italy

Roma, , Italy

Monterrey, Nuevo León, Mexico

Mexico City, , Mexico

San Luis Potosí City, , Mexico

Bełchatów, , Poland

Chełmno, , Poland

Karakow, , Poland

Kielce, , Poland

Kotarbinskiego, , Poland

Sosnowiec, , Poland

Torun, , Poland

Wroclaw, , Poland

Campulung Muscel, Argeş, Romania

Oradea, Bihor County, Romania

Cluj-Napoca, Cluj, Romania

Palazu Mare, Constanța County, Romania

Iași, Iaşi, Romania

Târgu Mureş, Munes, Romania

Bucharest, Sector 4, Romania

Saint Petersburg, Sankt-Peterburg, Russia

Smolensk, Smolensk Oblast, Russia

Moscow, , Russia

Samara, , Russia

Yaroslavl, , Russia

Vil. Stepanivka, Kherson Oblast, Ukraine

Dnipropetrovsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Poltava, , Ukraine

Vinnytsia, , Ukraine

Cambridge, Cambridgeshire, United Kingdom

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Exeter, , United Kingdom

London, , United Kingdom

Countries

United States; Argentina; Australia; Brazil; Colombia; Italy; Mexico; Poland; Romania; Russia; Ukraine; United Kingdom

Other Identifiers

2012-003209-92

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EVP-6124-016

Identifier Type: -

Identifier Source: org_study_id