E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004936 |
E.1.2 | Term | Bipolar depression |
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 |
To evaluate the relative efficacy of combination therapy with quetiapine plus lamotrigine and quetiapine monotherapy plus lamotrigine placebo in terms of improvement in depressive symptoms at 12 weeks in patients with bipolar depressive disorder.
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E.2.2 | Secondary objectives of the trial |
To compare adjunctive treatment with folic acid and folic acid placebo in terms of improvement in depressive symptoms at 12 weeks
To compare combination therapy with quetiapine plus lamotrigine with quetiapine monotherapy plus lamotrigine placebo AND folic acid with folic acid placebo in; - requirement for new treatments for depressive symptoms over 12 months - requirement for new treatments for manic symptoms over 12 months - continued remission from mood symptoms over 12 months - death (all cause and cause-specific including suicide) - dleiberate self-harm - quality of life (using the EuroQol EQ-5D scale) - unexpected adverse events - withdrawal from trial treatments due to adverse effects - cost-effectiveness
To explore possible subgroups effects: - type of bipolar disorder (I or II) - 5,10-Methylenetetrahydrofolate reductase (MTHFR) enzyme genotype - Catechol-o-methyltransferase (COMT) enzyme genotype - baseline homocysteine level - baseline folate level |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For randomisation: 1. primary diagnosis of DSM-IV bipolar disorder type I or II 2. consent to randomisation 3. aged 16 or over 4. current depressive episode requiring new pharmacological treatment 5. Quick Inventory of Depressive Symptomatology, self-report version (QIDS-SR16) score at least 11 6. uncertainty whether quetiapine plus lamotrigine would be more effective than quetiapine monotherapy 7. ability to tolerate quetiapine at a dose of at least 150mg/day 8. acceptable adherence to quetiapine (>90%) and self-report SMS satisfactory 9. Willing to accepr random allocation of treatments 10. in the opinion of the investigator, not currently experiencing manic or mixed episode.
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E.4 | Principal exclusion criteria |
For randomisation: 1. definite indications or contraindications to lamotrigine, quetiapine or folic acid* (including pregnancy and planned pregnancy) 2. new course of specific psychosocial intervention started in the past four weeks 3. first appointment for specific psychosocial intervention booked within the next 14 weeks 4. currently experiencing manic or mixed episode 5. primary diagnosis of schizophrenia
Plus, for women of child-bearing potential 6. not using adequate contraception or currently breast feeding.
* if contraindications are to folic acid/placebo only the person can enter the trial and be randomly allocated lamotrigine/placebo but not folic acid/placebo.
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E.5 End points |
E.5.1 | Primary end point(s) |
Improvement in depressive symptoms at 12 weeks from the date of randomisation using the Quick Inventory of Depressive Symptomatology, self-report version [QIDS-SR16]. |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | 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 | 50 |
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 | Yes |
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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Defined in the protocol as the last visit of the last trial participant. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |