Clinical trial NCT01556763: Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
Official title: A Double-Blind, Placebo-Controlled Randomized Study to Assess the Safety, Tolerability, and Pharmacokinetics of EVP-6124 in Participants With Schizophrenia on Stable Monotherapy With Selected Antipsychotics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Schizoaffective Disorder
Central Nervous System Diseases
Keywords: Schizophrenia
Schizoaffective
CNS
Lead sponsor: FORUM Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2012-03-16
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study in patients with schizophrenia is designed to provide preliminary evidence of the safety, tolerability, and pharmacokinetics as well as the effects on cognitive function of 2 doses of EVP-6124 compared with placebo when given with the patient's usual antipsychotic medication.

Detailed description: Study drug will be supplied as capsules and will be orally administered once daily for a total of 21 days. Eligible subjects will be admitted to an inpatient study unit on Day -6 (six days before the first dose of study drug is administered) and will remain confined to the inpatient study unit throughout the dosing phase. Safety assessments, PK sampling, and cognitive testing will be performed.

Eligibility criteria: Inclusion Criteria:

* Male or female aged 18 to 55 years (both inclusive).
* Females must be surgically sterile, post-menopausal, or using reliable contraception and have negative pregnancy tests at screening and at Day -1.
* A clinical diagnosis of schizophrenia or schizoaffective disorder and prescribed a stable dose of aripiprazole (10 to 30 mg/day), olanzapine (10 to 20 mg/day), paliperidone (3 to 12 mg/day), or risperidone (2 to 16 mg/day) for a minimum of 2 weeks before initial screening.
* In good general health and expected to complete the clinical trial as designed.
* Body Mass Index (BMI) of 18 kg/m\^2 to 38 kg/m\^2 (both inclusive) at screening.
* Adequate hearing, vision, and language skills to perform the cognitive testing and other procedures specified in the protocol.
* Voluntarily provided informed consent and signed an informed consent form (ICF) indicating that the purpose of the study was explained, and was willing and able to adhere to the study regimen and study procedures described in the ICF, including all confinement requirements.
* Negative urine drug screen at screening and inpatient observation baseline period (Day -6), except for a short-acting benzodiazepine if prescribed for insomnia.
* Fluent in English (speaking, writing, and reading).

Exclusion Criteria:

* Female subject who was pregnant or breast-feeding.
* Any active clinically significant medical condition within 1 month (30 days) prior to screening.
* A history of substance (drug) dependence or substance or alcohol abuse within the 12 months before randomization as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV).
* A score of \>5 on any item on the PANSS (Positive and Negative Syndrome Scale) Positive subscale at baseline during the inpatient observation period (Day -1).
* Any laboratory test abnormalities at screening indicating hepatic or renal dysfunction, or any other laboratory test abnormalities deemed by the investigator to be clinically significant.
* Any hematologic malignancy or solid tumor diagnosed within 3 years prior to study entry with the exception of localized skin cancer or carcinoma in situ of the cervix.
* Known to have had or was a carrier of HBsAg, HCV antibody, or had a positive result to the HIV-1 and/or HIV-2 antibodies.
* Uncooperative with or could not complete the study procedures.
* Received an investigational drug within 30 days before screening.
* Donated blood within 30 days before randomization on Day 1.

Primary outcomes:
measure: Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
timeFrame: Screening (Day -5 for continuous cardiac monitoring) to Day 22
measure: EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
timeFrame: Days 1 and 21
measure: EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole
timeFrame: Days 1 and 21
measure: EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
timeFrame: Days 1 and 21
measure: EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole
timeFrame: Days 1 and 21
measure: EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
timeFrame: Days 1 and 21
measure: EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
timeFrame: Days 1 and 21
measure: EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
timeFrame: Days 1 and 21
measure: EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
timeFrame: Days 1 and 21
Secondary outcomes:
measure: N100 Gating Ratio
timeFrame: Days -1 to 20
measure: P50 Amplitude Difference
timeFrame: Days -1 to 20
measure: MMN Summed Amplitude
timeFrame: Days -1 to 20
measure: P300 Peak Amplitude
timeFrame: Days -1 to 20
Other outcomes:
Locations:
city: Wichita
country: United States
facility: Clinical Research Institute
state: Kansas
Study officials:
affiliation: Clinical Research Institute
name: Sheldon H. Preskorn, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Preskorn SH, Gawryl M, Dgetluck N, Palfreyman M, Bauer LO, Hilt DC. Normalizing effects of EVP-6124, an alpha-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract. 2014 Jan;20(1):12-24. doi: 10.1097/01.pra.0000442935.15833.c5.