E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bipolar Disorder (mania and hypomania) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000852 |
E.1.2 | Term | Acute Mania |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021030 |
E.1.2 | Term | Hypomania |
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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 |
To investigate whether Circadin is able to contribute to a reduction of hypomanic or manic symptoms in acute bipolar disorder. The primary outcome measure is a 3 point reduction of the score on the Young Mania Rating Scale (YMRS). |
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E.2.2 | Secondary objectives of the trial |
1. Activity, sleep architecture and environmental light intensity using the Actiwatch – L. 2. Quick Inventory of Depressive Symptoms – clinician report version (QIDS-C16) (Rush et al. 2003) to provide a measure of the severity of depressive symptoms. 3. Quick Inventory of Depressive Symptoms – self report version (QIDS-SR16 ) (Rush et al. 2003). 4. Altman Self-rating Scale for Manic Symptoms (Altman et al. 1997) to provide more frequent self-assessment of manic symptoms. 5. Leeds Sleep Evaluation Questionnaire (Zisapel and Laudon, 2003) 5. Adverse events. 6. Sex hormone levels on three occasions – testosterone, progesterone and oestrogen. 7. Melatonin levels at base-line and at two weeks measured by 24 hour urinary melatonin. 8. Genetic analysis may allow investigation of a genetic contribution to the possible effect of circadin on the other indices being measured. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: • In or outpatients meeting DSM-IV criteria for bipolar disorder type 1 or 2 • Currently experiencing manic or hypomanic symptoms. • Minimum score on Young Mania Rating Scale (YMRS) (>/=20) • Informed consent possible or previously obtained. • Willing to allow his or her General Practitioner and consultant to be notified of participation in the study. • Aged 18-65 |
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E.4 | Principal exclusion criteria |
Exclusion Criteria: The participant may not enter the study if ANY of the following apply: • Clinically significant illicit substance or alcohol misuse where dependence criteria are satisfied – craving on abstinence, withdrawal symptoms develop and are relieved by the substance, an effect on the behavioural activity of the individual to procure the substance on a predictable basis and an effect on the socio-occupational or relational functioning of the individual. • Comorbid Axis 1 disorders (according to DSM-4 Diagnostic Classification system). • Significant abnormalities on physical examination at the commencement of the trial, necessitating further investigation by a General Practitioner. • Patients currently taking Beta-blocker type medication . Patients suffering from auto-immune disease. • Patients taking the SSRI anti-depressant fluvoxamine, 5- and 8- methoxypsoralens, hormonal medications, quinolones or cimetidine, as these could interact with the drug to increase melatonin levels. • Patients taking carbamazepine or rifampicin, as these could interact with the drug to reduce melatonin levels.. . Females who are pregnant or breast-feeding. . Patients who have to undertake tasks where drowsiness could increase risk. |
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E.5 End points |
E.5.1 | Primary end point(s) |
A reduction of three points on the Young Mania Rating Scale (YMRS). |
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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 | 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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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
|
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |