Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia

NCT01556763 | Completed Phase 1 Results

• 1 other identifier: EVP-6124-005
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Central Nervous System Diseases

Keywords

Schizophrenia; Schizoaffective; CNS

Outcome Measures

Primary Outcomes (9)

• Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.

  Safety and tolerability was measured by number of reported adverse events (serious and non-serious) and repeated clinical evaluation of physical examinations, vital signs, 12-lead electrocardiogram (ECG), 24-hour continuous cardiac monitoring, and laboratory tests (hematology/blood chemistry/urinalysis).

  Screening (Day -5 for continuous cardiac monitoring) to Day 22

• EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole

  Blood samples for pharmacokinetic (PK) analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

• EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole

  Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

• EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole

  Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

• EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole

  Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

• EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone

  Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

• EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone

  Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

• EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone

  Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

• EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone

  Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

  Days 1 and 21

Secondary Outcomes (4)

• N100 Gating Ratio

  Days -1 to 20

• P50 Amplitude Difference

  Days -1 to 20

• MMN Summed Amplitude

  Days -1 to 20

• P300 Peak Amplitude

  Days -1 to 20

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Matching placebo was administered as one capsule per day for 21 days.

Drug: Placebo; Drug: Antipsychotic therapy

EVP-6124 (1.0 mg/day)

EXPERIMENTAL

EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.

Drug: EVP-6124 (1.0 mg/day); Drug: Antipsychotic therapy

EVP-6124 (0.3 mg/day)

EXPERIMENTAL

EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.

Drug: EVP-6124 (0.3 mg/day); Drug: Antipsychotic therapy

Interventions

EVP-6124 (0.3 mg/day) DRUG

EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.

EVP-6124 (0.3 mg/day)

EVP-6124 (1.0 mg/day) DRUG

EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.

EVP-6124 (1.0 mg/day)

Placebo DRUG

Matching placebo was administered as one capsule per day for 21 days.

Placebo

Antipsychotic therapy DRUG

Concomitant therapy with antipsychotic medication (aripiprazole \[10 to 30 mg/day\], olanzapine \[10 to 20 mg/day\], paliperidone \[3 to 12 mg/day\], or risperidone \[2 to 16 mg/day\]), taken at the same time each day as the EVP-6124 dose. Patients must have been taking concomitant therapy for at least 2 weeks at a stable dose to be eligible for the study.

EVP-6124 (0.3 mg/day); EVP-6124 (1.0 mg/day); Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• FORUM Pharmaceuticals Inc: lead

Study Sites (1)

Clinical Research Institute

Wichita, Kansas, 67211, United States

Location

Related Publications (1)

• 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.

  PMID: 24419307 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Central Nervous System Diseases

Interventions

7-chloro-N-quinuclidin-3-yl-benzo(b)thiophene-2-carboxamide

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Nervous System Diseases

Results Point of Contact

• Title: Maria Gawryl, Ph.D., Vice President, Regulatory Affairs & Drug Development
• Organization: EnVivo Pharmaceuticals, Inc.

mgawryl@envivopharma.com

617-225-4264

Study Officials

• Sheldon H. Preskorn, M.D.

  Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2012
• First Posted: March 16, 2012
• Study Start: April 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: June 21, 2012
• Results First Posted: June 21, 2012

Record last verified: 2012-05

Locations

US (1)