SchizophreniaPhase 1NCT01556763
Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
A Phase 1 study testing EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day) and Antipsychotic therapy in people with Schizophrenia and Schizoaffective Disorder, run by FORUM Pharmaceuticals Inc at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Central Nervous System Diseases
- What is being tested?
- EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day) and Antipsychotic therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Aug 2008
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day), Placebo, Antipsychotic therapy
- Keywords
- Schizophrenia, Schizoaffective, CNS
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EVP-6124 (0.3 mg/day)Drug
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
EVP-6124 (1.0 mg/day)Drug
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
PlaceboDrug
Matching placebo was administered as one capsule per day for 21 days.
Antipsychotic therapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching placebo was administered as one capsule per day for 21 days. Receives: 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. Receives: 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. Receives: Drug: EVP-6124 (0.3 mg/day); Drug: Antipsychotic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Days 1 and 21
Secondary outcomes (4)
N100 Gating Ratio
N100 auditory evoked potential response (amplitude measured in microvolts) using the sensory gating paradigm. Measured by electroencephalography (EEG) as the amplitude ratio of test stimulus to conditioning stimulus. Plotted on a unitless scale of 0 to 2. Normalization is suggested by a lower value.
Measured: Days -1 to 20
P50 Amplitude Difference
P50 auditory evoked potential response (amplitude measured in microvolts) using sensory gating paradigm. Measured by EEG as amplitude difference (conditioning stimulus minus test stimulus). Plotted on a scale of -0.2 to 0.8 microvolts. Normalization is suggested by a higher value.
Measured: Days -1 to 20
MMN Summed Amplitude
Mismatch negativity (MMN) auditory evoked potential response (amplitude in microvolts) using orienting paradigm. Measured by EEG and calculated as the voltage difference over 100-200 msec following stimulus onset (rare stimulus minus frequent stimulus). Plotted on a scale of -1.2 to 0.2 microvolts. Normalization is suggested by a more negative value.
Measured: Days -1 to 20
P300 Peak Amplitude
P300 auditory evoked potential response (amplitude in microvolts) using orienting paradigm. Measured by EEG and calculated as the peak amplitude over 250-500 msec following stimulus onset (rare stimulus minus frequent stimulus). Plotted on a scale of -0.4 to 1.2 microvolts. Normalization is suggested by a more positive value.
Measured: Days -1 to 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2012 (estimated)
- Study startApr 2008
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- FORUM Pharmaceuticals Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sheldon H. Preskorn, M.D., Principal investigator, Clinical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01556763
- Sponsor's protocol ID
- EVP-6124-005
- Status last verified
- May 2012
- First submitted
- 14 Mar 2012
- Last updated
- 21 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24419307
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01556763
- Acronym / sponsor ID
- EVP-6124-005
- Keywords
- Schizophrenia, Schizoaffective, CNS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- FORUM Pharmaceuticals IncIndustry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 16 Mar 2012 (estimated)
- Results
- Posted 21 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Drug: Antipsychotic therapyMatching placebo was administered as one capsule per day for 21 days. |
| EVP-6124 (1.0 mg/day) | Experimental | Drug: EVP-6124 (1.0 mg/day), Drug: Antipsychotic therapyEVP-6124 was administered as one 1.0 mg capsule per day for 21 days. |
| EVP-6124 (0.3 mg/day) | Experimental | Drug: EVP-6124 (0.3 mg/day), Drug: Antipsychotic therapyEVP-6124 was administered as one 0.3 mg capsule per day for 21 days. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EVP-6124 (0.3 mg/day)EVP-6124 was administered as one 0.3 mg capsule per day for 21 days. | Drug | EVP-6124 (0.3 mg/day) |
| EVP-6124 (1.0 mg/day)EVP-6124 was administered as one 1.0 mg capsule per day for 21 days. | Drug | EVP-6124 (1.0 mg/day) |
| PlaceboMatching placebo was administered as one capsule per day for 21 days. | Drug | Placebo |
| Antipsychotic therapyConcomitant 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. | Drug | EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day), Placebo |
Primary outcome
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
Time frame: Screening (Day -5 for continuous cardiac monitoring) to Day 22
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).
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
Time frame: Days 1 and 21
Blood samples for pharmacokinetic (PK) analyses were taken before dosing with EVP-6124 on Days 1 and 21.
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole
Time frame: Days 1 and 21
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
Time frame: Days 1 and 21
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole
Time frame: Days 1 and 21
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
Time frame: Days 1 and 21
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
Time frame: Days 1 and 21
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
Time frame: Days 1 and 21
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
Time frame: Days 1 and 21
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
4 secondary outcomes
N100 Gating Ratio
Time frame: Days -1 to 20
P50 Amplitude Difference
Time frame: Days -1 to 20
MMN Summed Amplitude
Time frame: Days -1 to 20
P300 Peak Amplitude
Time frame: Days -1 to 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24419307Preskorn 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sheldon H. Preskorn, M.D. principal investigator
Clinical Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day) and Antipsychotic therapy in people with Schizophrenia and Schizoaffective Disorder, run by FORUM Pharmaceuticals Inc at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator. (time frame: Screening (Day -5 for continuous cardiac monitoring) to Day 22). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01556763, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2012.