E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
To assess the efficacy of Amibegron 350 mg twice a day compared to placebo in the prevention of relapse of anxiety, in improved patients with generalized anxiety disorder (GAD), over a 24 to 52-week treatment period. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of Amibegron on the secondary efficacy criteria. The secondary efficacy criteria will be the change from baseline (V7) of: • Clinical Global Impression (CGI) Severity of Illness score. • Hamilton Anxiety Rating Scale (HAM-A).
To assess the safety and tolerability of Amibegron in patients with generalized anxiety disorder. The safety criteria will be the following: • Vital signs (including weight) • Spontaneously-reported adverse events • Clinical laboratories • Physician Withdrawal Checklist (PWC) • Montgomery and Asberg depression rating scale (MADRS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For entry into the open phase: Patients suffering from generalized anxiety disorder, according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria and assessed with the Mini International Neuropsychiatric Interview (MINI) (7) plus GAD module with a total score on the 14-item Hamilton Anxiety Rating Scale (HAM-A) ≥ 20 at V1(D-4) and V2 (D-1).
For entry into the double-blind randomized phase: Improved patients with HAM-A score < 11 at V7 (W12). |
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E.4 | Principal exclusion criteria |
Related to study methodology 1. Inpatients. 2. Patients < legal age of majority. 3. Patients unable to give voluntarily their written informed consent to participate in the whole study or to comply with the protocol and follow written and verbal instructions. 4. Patients with a diagnosis of Major Depressive Disorder as defined by DSM IV-TR within 6 months of screening. 5. Patients with a Montgomery and Asberg Depression Rating Scale (MADRS) (9) total score > 18 at screening (Visit 1, Day -4) or baseline (Visit 2, Day -1). 6. Patients at immediate risk for suicidal behavior based on an unstructured clinical interview; or who have, before first study drug intake [at either the screening (V1) or baseline (V2) visits]: • A score of > 5 on the suicidal thoughts item of the MADRS • Or, a current suicide risk score ≥10 from module C of the (MINI). 7. Patients with other current (within 6 months) anxiety disorder according to the MINI of: • Panic disorder, • Agoraphobia, • Social phobia, • Obsessive compulsive disorder (OCD), • Post-traumatic stress disorder (PTSD). 8. Patients with a lifetime history according to the MINI of: • Bipolar disorder, • Psychotic disorder, • Antisocial personality disorder. 9. Patients with a current history according to the MINI of: • Anorexia nervosa or bulimia nervosa in the past 6 months • Alcohol dependence or abuse or substance dependence or abuse in the past 12 months, except nicotine or caffeine dependence. 10. Patients who have used the following medications prior to screening: • Any continuous use of anxiolytic (e.g., benzodiazepines, buspirone) or hypnotic (e.g., zolpidem, zaleplon) within 2 weeks. Chronic means more than 2 days per week. • Any antipsychotic within 3 months, • Any antidepressant within 4 weeks, • Any mood-stabilizer (lithium, anticonvulsants) within 4 weeks. 11. Treatment with electroconvulsive therapy (ECT) or rapid Transcranial Magnetic Stimulation (r TMS) within 3 months prior to screening. 12. Patients who have initiated, stopped, or changed the frequency or nature of psychotherapy within 3 months prior to screening. 13. Patients with severe or unstable concomitant medical conditions (cardiovascular, neurological, gastrointestinal, hepatic, renal, endocrinologic, rhumatologic) according to the investigator's judgment that would impact the assessment of the study drug. 14. History of seizures other than a single childhood febrile seizure. 15. Patients with clinically significant abnormal laboratory value at screening, e.g. ALT or AST > 2 times upper limit of normal range (ULN), hemoglobin < 12g / 100ml for male and < 11g / 100ml for female, neutrophils < 1500/mm3, platelets < 100 000/mm3, creatinine ≥ 150 µmol/l. 16. Patients with clinically significant ECG findings or positive results on the urine drug screen at screening. 17. Patients who have taken an investigational drug in the last 3 months prior to screening. 18. Any patient who has previously participated in a Amibegron protocol. 19. Females of childbearing potential with a positive β-HCG pregnancy test at screening, or not using an effective method of birth control during the entire study period (i.e. birth control pill, intrauterine device, hormonal injection, sterilization or barrier method plus spermicide) and females pregnant or lactating.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary criterion is the time to relapse of anxious symptoms (in days) from randomization date defined by any one of the following criteria: • HAM-A total score ≥ 15 confirmed at a subsequent visit 2 weeks later unless the patient drops out, or • Any drop-out for lack of efficacy (according to investigator’s decision based on his/her knowledge of the patient), or • Prescription/use of alternative or additional treatments (pharmacological or nonpharmacological) for relief of psychiatric symptoms. |
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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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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The overall end of study is defined by the date of the last follow-up visit of the last randomized patient to complete 24 weeks of double-blind treatment without experiencing relapse. At that time, the study will be stopped and the patients under double-blind treatment will have to stop their treatment at the next planned visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |