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

NCT ID: NCT01714661

Last Updated: 2016-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 753 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2015-12-31

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, 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

EVP-6124, Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Arm 3

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

Tucson, Arizona, United States

Anaheim, California, United States

Bellflower, California, United States

Costa Mesa, California, United States

Culver City, California, United States

Downey, California, United States

Escondido, California, United States

Los Angeles, California, United States

Oceanside, California, United States

Orange, California, United States

San Diego, California, United States

Torrance, California, United States

Lauderhill, Florida, United States

Miami, Florida, United States

North Miami, Florida, United States

Orange City, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Wichita, Kansas, United States

Shreveport, Louisiana, United States

Minneapolis, Minnesota, United States

Flowood, Mississippi, United States

Creve Coeur, Missouri, United States

O'Fallon, Missouri, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Marlton, New Jersey, United States

Albuquerque, New Mexico, United States

Cedarhurst, New York, United States

New York, New York, United States

Charlotte, North Carolina, United States

Durham, North Carolina, United States

Cleveland, Ohio, United States

Oklahoma City, Oklahoma, United States

Conshohocken, Pennsylvania, United States

Norristown, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Dallas, Texas, United States

La Plata, Buenos Aires, Argentina

Caba, Buenos Aires F.D., Argentina

Córdoba, Córdoba Province, Argentina

Mendoza, Mendoza Province, Argentina

Melbourne, , Australia

Rio de Janeiro, Rio de Janeiro, Brazil

Itapira, São Paulo, Brazil

São Paulo, , Brazil

Calgary, Alberta, Canada

Penticton, British Columbia, Canada

Chatham, Ontario, Canada

Kingston, Ontario, Canada

Montreal, Quebec, Canada

Achim, , Germany

Berlin, , Germany

Düsseldorf, , Germany

Freiburg im Breisgau, , Germany

Leipzig, , Germany

Mittweida, , Germany

München, , Germany

Regebsburg, , Germany

Regensburg, , Germany

Stralsund, , Germany

Wiesbaden, , Germany

México, D.F, Mexico

Guadalajara, Jalisco, Mexico

Monterrey, Neuvo Leon, Mexico

Bialystok, , Poland

Gdansk, , Poland

Lodz, , Poland

Lublin, , Poland

Torun, , Poland

Tuszyn, , Poland

Warsaw, , Poland

Talagi, Arkhangelskaya oblast, Russia

Moscow, Moscow, Russia

Saint Petersburg, Sankt-Peterburg, Russia

Stavropol, , Russia

Belgrade, , Serbia

Kragujevac, , Serbia

Niš, , Serbia

Novi Kneževac, , Serbia

Singapore, Singapore, Singapore

Barcelona, Barcelona, Spain

Mataró, Barcelona, Spain

Salamanca, Castille and León, Spain

Zamora, Castille and León, Spain

Alcorcón, Madrid, Spain

Coslada, Madrid, Spain

Madrid, Madrid, Spain

Vigo, Pontevedra, Spain

Donetsk, , Ukraine

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Luhansk, , Ukraine

Countries

United States; Argentina; Australia; Brazil; Canada; Germany; Mexico; Poland; Russia; Serbia; Singapore; Spain; Ukraine

Other Identifiers

2012-003208-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EVP-6124-015

Identifier Type: -

Identifier Source: org_study_id