E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalised anxiety disorder |
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E.1.1.1 | Medical condition in easily understood language |
Generalised anxiety disorder |
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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 | LLT |
E.1.2 | Classification code | 10018105 |
E.1.2 | Term | Generalized anxiety disorder |
E.1.2 | System Organ Class | 100000004873 |
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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 |
Though the pharmacological actions of pregabalin are fairly well characterised in animal models, there is little understanding of how it might modulate the emotionrelated functions of neural systems thought to underlie GAD, such as amygdala hyperactivity and prefrontal hypoactivity. The purpose of this study is to clarify the effects of pregabalin on two measures the startle response and an antisaccade task as increased knowledge of the effects of pregabalin on these neural systems in a clinical sample would permit a greater understanding of its possible mechanism of action, and this in turn could lead to refined treatment approaches. |
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E.2.2 | Secondary objectives of the trial |
The study is not designed to have sufficient power to ascertain the efficacy of pregabalin in augmentation treatment, partly because this has already been established in a large randomised placebo controlled trial. However the use of detailed questionnaires and questions regarding tolerability will allow an evaluation of the effectiveness and acceptability (or otherwise) of pregabalin, in patients who are more representative of those seen within wider clinical practice. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
• Male or female patients aged between 18-70 years
• DSM-IV diagnosis of generalized anxiety disorder (GAD)
• Historical evidence of treatment of current symptoms with an SSRI or SNRI for at least 6 weeks
• At least ‘moderately ill’ on the Clinical Global Impression of Severity (score of 4 or more)
• Anxiety symptoms of at least moderate severity (i.e. 24 or more on the Hamilton Anxiety Scale)
• Depressive symptoms of not more than mild severity (i.e. less than 20 on the MADRS)
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E.4 | Principal exclusion criteria |
Exclusion criteria
• Male or female patients aged less than 18 or more than 70 years
• Primary diagnosis other than GAD
• No historical evidence of treatment of current symptoms with an SSRI or SNRI for at least 6 weeks
• Less than moderately ill on the Clinical Global Impression of Severity (CGI-S score of 3 or less)
• Anxiety symptoms of less than moderate severity (i.e. 23 or less on the Hamilton Anxiety Scale)
• Depressive symptoms of more than mild severity (i.e. 20 or more on the MADRS)
• A primary diagnosis of an alcohol or substance use disorder
• DSM-IV diagnosis of antisocial personality disorder, according to completion of the MINI
• Pregnant/breastfeeding women.
Patients with a primary substance abuse or dependence disorder will be excluded from participating in the study, but those with secondary substance abuse (not dependence) could be included, providing that it had temporally arisen during the ‘index episode’ of GAD, that the symptoms were regarded as being secondary to the GAD, and that the nature of the substance use was such that treatment with an SSRI or SNRI was not inadvisable.
Patients with coexisting depressive symptoms could be included, if the patient and the doctor considered GAD was the primary diagnosis based on symptom severity and distress. However if the patient scored 20 or more on the Montgomery-Asberg
Depression Rating Scale (MADRS) (Montgomery & Asberg, 1979) they would be excluded from participation in the study. The MINI includes a module to identify antisocial personality disorder, and patients who meet the criteria for this condition will be excluded from the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
baseline, Week 2, Week 4 and Week 6 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline, Week 2, Week 4 and Week 6 |
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E.5.2 | Secondary end point(s) |
baseline, Week 2, Week 4 and Week 6 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline, Week 2, Week 4 and Week 6 |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
effects on neuro-cognitive functioning |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
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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 | |
E.8.9.1 | In the Member State concerned days | |