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Phase 1 N=21 Randomized Triple-blind Treatment

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

Schizophrenia · Schizoaffective Disorder · Central Nervous System Diseases

Enrolled (actual)
21
Serious AEs
4.8%
Results posted
Jun 2012
Primary outcome: Primary: Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator. — 0; 0; 1; 0 participants

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
EVP-6124 (0.3 mg/day) (Drug); EVP-6124 (1.0 mg/day) (Drug); Placebo (Drug); Antipsychotic therapy (Drug)
Age
Adult · 18+ yrs
Sex
All
Sponsor
FORUM Pharmaceuticals Inc
Primary completion
Aug 2008

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
0; 0; 1; 0; 5; 5
PRIMARY
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
581.0; 210.0; 2058.6; 968.3
PRIMARY
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole
8.0; 8.0; 6.0; 8.0
PRIMARY
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
10,966; 3838; 42,042; 20,560
PRIMARY
EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole
39.0; 43.1; NA; 116.6
PRIMARY
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
315.0; 165.0; 1510.0; 545.4
PRIMARY
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
6.0; 8.0; 6.0; 8.0
PRIMARY
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
6359; 3110; 33,042; 11,888
PRIMARY
EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
92.0; 45.8; NA; 78.1
SECONDARY
N100 Gating Ratio
1.648; 0.801; 0.951 =0.10
SECONDARY
P50 Amplitude Difference
-0.17; 0.67; -0.06 =0.07
SECONDARY
MMN Summed Amplitude
0.14; -1.15; -0.61 =0.02 sig
SECONDARY
P300 Peak Amplitude
-0.3; 1.08; 0.78 =0.008 sig

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.

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01556763). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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