E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Anxiety Disorder (GAD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018075 |
E.1.2 | Term | Generalised anxiety disorder |
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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 |
The main objective of this study is to conduct a preliminary evaluation of the safety and efficacy of the narrow-leaved coneflower root (Echinaceae angustifoliae radix) dry extract as compared to placebo for the treatment of generalized anxiety disorder (GAD) in order to gather data to estimate intervention parameters (i.e to quantify an estimate of possible effect) and to provide an estimate of the variance as this variance may be used in a formal sample size calculation in a subsequent study. The context of the justifications for this pilot study is that future study(s) will use the information from it in its/their design. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of GAD (Diagnostic and Statistical Manual-IV [DSM-IV], 300.02) based on a structured Mini-International Neuropsychiatric Interview 2. Subjects must have a HAM-A total score ≥17 and ≤25 at the screening (V1) and randomization (V2) visits. On items 1 (anxious mode) and 2 (tension) a score of 2 or more will be required. 3. Subjects must have a total score of ≤10 on Beck scale Subject must have a ≥3 point on CGI 5. Otherwise healthy men or non-pregnant, non-lactating women (women must be using a hormonal or barrier method of contraception or be postmenopausal or surgically sterilized). Healthy is defined as no other clinically relevant abnormalities identified by a detailed medical history, full physical examination including sitting blood pressure (BP) and heart rate measurement. 6. Age 18 to 60 years, inclusive. 7. All women must have negative pregnancy tests at the Screening (V1) and Randomization (V2) visits. 8. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed and understood of all pertinent aspects of the study. 9. Subjects who are willing and able to comply with scheduled visits, treatment plan, and other study procedures. |
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E.4 | Principal exclusion criteria |
1.Subjects with evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, pancreatic, neurologic, active infections, immunological, or allergic disease (including drug allergies). 2. Any of the following current (within the past 6 months through the present) DSM-IV Axis I diagnoses: o Major depressive disorder; o Obsessive compulsive disorder; o Panic disorder; o Agoraphobia; o Posttraumatic stress disorder; o Anorexia; o Bulimia; o Caffeine-induced anxiety disorder; o Alcohol or substance abuse or dependence unless in full remission for at least 6 months; o Social anxiety disorder 3. Any of the following past or current DSM-IV Axis I diagnoses: o Schizophrenia; o Psychotic disorder; o Delirium, dementia, amnestic, and other clinically significant cognitive disorders; o Bipolar or schizoaffective disorder; o Cyclothymic disorder; o Dissociative disorders Antisocial or borderline personality disorder. 5. Serious suicidal risk per the clinical investigator's judgment. (Note: The Suicidality module of the MINI diagnostic interview should be used as aid to the assessment of suicidality, but does not replace overall clinical judgment in determination of suicidal risk). 6. Current use of psychotropic medications (ie, drugs normally prescribed for depression, mania, anxiety, insomnia, or psychosis) that cannot be discontinued 2 weeks prior to randomization. Fluoxetine is prohibited within 5 weeks of randomization. In the event of inadvertent administration of psychotropic medications during the 2 weeks prior to randomization, continued eligibility will be assessed on a case by case basis by the investigator and the medical monitor. 7. Use of drugs, supplements, prescription or nonprescription, or food that have psychoactive properties. In the event of inadvertent use of such products during the 2 weeks prior to randomization, continued eligibility will be assessed on a case by case basis by the investigator and the medical monitor. 8. Subjects who have been treated with monoamine oxidase inhibitors in the 14 days prior to the baseline visit. 9. Regular use of benzodiazepines during the 3 months prior to Screening (for at least 5 out of 7 days per week). 10. Subjects initiating formal psychotherapy within 3 month prior to screening who intend to continue formal psychotherapy during the study. This includes psychodynamic, cognitive, and interpersonal therapies. 11. Positive drug tests at Screening or Randomization visits for any of the following substances or classes of compounds: amphetamines, barbiturates, opiates, benzodiazepines, sedatives and hypnotics, cocaine, phencyclidine (PCP), cannabinoids, or other illegal or illicit drugs. 12. Any condition possibly affecting drug absorption (eg, gastrectomy). 13. Subjects with a current seizure disorder. 14. Subjects with a history of life-threatening neoplasms within 5 years prior to study entry, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin. 15. Subjects with earlier known hypothyroidism or hyperthyroidism, except subjects who are euthyroid and have been on stable doses of thyroid replacement for 6 months or more. 16. Subjects with any earlier diagnosed and at the time of enrolment clinically unstable hematological, autoimmune, endocrine, neurological, renal, hepatic, retinal, gastrointestinal, or cardiovascular disorder. 17. History of allergy or intolerance to any Echinaceae product. 18. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception for the duration of the study. 19. Treatment with an investigational drug within 60 days preceding the first dose of trial medication. 20. Other severe acute or chronic medical or psychiatric condition that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: Detectable differences in the mean changes on the Hamilton Anxiety Scale in Echinacea and Placebo groups Secondary efficacy endpoints (only exploratory): Proportion of patients not responding to treatment, Proportion of patients with mild response, defined as 25% improvement on the HAM-A scale Proportion of patients with marked response defined as 50% improvement on HAM-A scale Proportion of fully recovered patients defined as decrease on HAM-A scale below 7 point Time to symptom improvement defined as time required for 25%, 50% improvement or decrease of HAM-A scale below 7 point The mean changes in psychic and somatic subscales of the Hamilton anxiety scales Changes in items 1 and 2 of the Hamilton anxiety scale (i.e. cardinal symptoms of anxiety disorders (anxiety, excessive worry, tension) Mean change from baseline of Clinical Global Impression severity of illness scale (CGI) Mean change from baseline on the anxiety subscale of the patients rated Hospital Anxiety and Depression Scale, its anxiety component only (HADS-A) Mean change from baseline on the Perceived Stress Scale Safety endpoints: Safety assessments will consist of monitoring and recording all adverse events including serious adverse events, vital signs, physical condition and body weight. The safety endpoints are: Incidence of adverse events; Physical examination; Vital signs |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 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.8.3 |
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 | 5 |
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 | Information not present in EudraCT |
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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |