E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cognitive impairment associated with schizophrenia |
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E.1.1.1 | Medical condition in easily understood language |
Cognitive impairment associated with schizophrenia |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To pilot the approach of combining a cognitive-enhancement drug with cognitive training in patients with schizophrenia
2. To obtain proof-of-concept evidence for the direction of effect and develop the first estimates of effect sizes that can guide future developments |
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E.2.2 | Secondary objectives of the trial |
1. To examine the reliability of CogState Schizophrenia Battery[95] and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery (MCCB)[96, 97] in the face of repeated testing
2. To examine the sensitivity of CogState and MCCB to a single dose of modafinil in patients with schizophrenia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• DSM-IV diagnosis of schizophrenia or schizoaffective disorder confirmed by Mini International Neuropsychiatric Interview (MINI)
• Age between 18 and 60 years
• Gender: Males and Females
• Normal baseline electrocardiogram (ECG)
• Duration of illness equal to or greater than one year
• Patients should be clinically stable in a non-acute phase for at least 8 weeks prior to the screening visit
• Subjects will meet the following symptom criteria
• Positive and Negative Syndrome Scale (PANSS) Conceptual Disorganization item score ≤ 4
• PANSS Hallucinatory Behaviour or Unusual Thought Content item scores ≤ 4
• PANSS Negative Subscale scores on all items ≤ 4
• Subjects will meet the following cognitive performance criteria
• Raw score of 6 or greater on the Wechsler Test of Adult Reading (WTAR)
•Treatment with stable doses of atypical antipsychotics or stable doses of typical antipsychotics in the absence of concomitant anticholinergics for at least 4 weeks prior to the screening visit
• Negative result in the urine pregnancy test performed during the screening visit in women of childbearing potential (not surgically sterile or 2 years postmenopausal)
• Women of child-bearing potential, who are sexually active, will be considered as potential participants if they are using acceptable methods of contraception, which include barrier method with spermicide, intrauterine device (IUD), steroidal contraceptive (oral, transdermal, implanted, and injected). Women on combined and progestogen-only contraceptives and on contraceptive patches and vaginal rings will be required to use additional contraceptive precautions for the duration of the trial and 4 weeks after stopping taking modafinil for the study purposes because modafinil may reduce the effectiveness of both combined and progestogen-only contraceptives
• Subjects must read and write in English at a level sufficient to understand and complete study-related procedures
• Written and witnessed informed consent |
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E.4 | Principal exclusion criteria |
• DSM-IV diagnosis of alcohol or substance abuse (other than nicotine) within the last month or a DSM-IV diagnosis of alcohol or substance dependence (other than nicotine) in the last 6 months preceding the screening visit
• Treatment with clozapine
• Treatment with modafinil
• Current treatment (within 4 weeks) with psychotropic agents known to affect cognition: amphetamines, barbiturates, lithium, MAOIs, methylphenidate, benzodiazepines, anticholinergics
• Current treatment (within 4 weeks) with cyclosporine (modafinil reduces plasma concentration of cyclosporine), phenytoin (modafinil possibly increases plasma concentration of phenytoin), anticoagulants (modafinil increases the levels of anticoagulants), tricyclic antidepressants (modafinil may increase their levels)
• Evidence of tardive dyskinesia, tardive dystonia or other severe
chronic movement disorders on physical examination
• History of neuroleptic malignant syndrome
• Pregnant or breast-feeding women
• Clinically significant abnormalities on physical examination
• History of a serious neurological disorder or a systemic illness with known neurological complications
• Hypertension, arrhythmia, left ventricular hypertrophy, cor pulmonale, or clinically significant signs of CNS stimulant-induced mitral valve prolapse (including ischemic ECG changes, chest pain and arrhythmias), which pose a risk to the patient if they were to participate in the study
• Any known drug allergies, including sensitivity to modafinil, and the development of drug-associated rash in the past
• Unwillingness or inability to follow or comply with the procedures outlined in the protocol
• Prior participation in a clinical trial of any psychotropic medication in the last 2 months preceding the screening visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is the effect of the combination of modafinil and cognitive training on learning capacity of the research participants, i.e. the percentage of correct responses and mean response time (for correct responses only) as a function of cognitive training |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluated every day throughout 12 day study period. |
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E.5.2 | Secondary end point(s) |
The mean response time (for correct responses only) as function of cognitive training, CogState and MCCB measures. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluated every day throughout 12 day study period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The trial will be completed at the last visit of the the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |