E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with bipolar disorder meeting DSM-5 criteria for hypomania or mania |
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E.1.1.1 | Medical condition in easily understood language |
Bipolar disorder is characterised by periods of elevated mood and periods of depression. The elevated mood is known as hypomania or mania: an individual feels abnormally happy, energetic or irritable. |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000852 |
E.1.2 | Term | Acute mania |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021030 |
E.1.2 | Term | Hypomania |
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 |
The principle research objective is to compare the effect of ebselen versus placebo as an 'add on' treatment to help stabilise hypo/manic symptoms in bipolar disorder. The primary outcome measure will be the difference in the clinician-rated Young Mania Rating Scale (YMRS) between the two groups and this will be measured at the screening interview and weekly throughout the trial, which lasts a total of four weeks. |
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E.2.2 | Secondary objectives of the trial |
To investigate whether ebselen, compared to placebo, is able to improve clinician and self-rated mania, depression and sleep symptoms. Also to see if ebselen is able to improve day to day activity (circadian) rhythms and reduce over activity measured using a wrist worn monitor, similar to a wrist watch.
To observe any adverse events and whether those taking ebselen have reduced overall use of concomitant medication compared to placebo. Also to determine how successful the study is in keeping secret whether or not individuals were taking the active or placebo treatments throughout the trial using questionnaires.
Also to check compliance using capsule count and record checking and to determine whether the participants and researchers could guess whether participants had been given ebselen or placebo using a Visual Analogue Scales and to look at the success of PPI engagement.
Finally to investigate ebselen levels and markers of inflammationin in plasma.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participant is willing and able to give informed consent for participation in the trial. • Male or Female aged 18-70 years • Diagnosed with bipolar disorder, screened using the SCID to meet DSM-5 criteria for Manic or Hypomanic Episode. • Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial • In the Investigator’s opinion, is able and willing to comply with all trial requirements. • The Clinical/GP team treating the patient are in agreement with the patient's participation
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E.4 | Principal exclusion criteria |
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. • Known significant renal or hepatic impairment. • Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. • Participants who have participated in another research trial involving an investigational product in the past 12 weeks. • Clinically significant illicit substance or alcohol misuse where dependence criteria are satisfied. • Taking lithium.
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in the Young Mania Rating Scale (YMRS) between placebo and ebselen groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline and weekly for 4 weeks. The main time point is at the end of week three before ebselen is stopped. |
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E.5.2 | Secondary end point(s) |
Clinician-rated CGI-BP mania scale Self-rated ASRM Clinician-rated HAM-D Self-rated QIDS Actigraphy Self-rated LSEQ Self-rated Adverse effects Concomitant medication recorded Researcher and participant blinding questionnaire Compliance: capsule count and records checked Randomisation Guess VAS PPI questionnaire
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints measured up to 3 x weekly throughout the trial. Actigraphy will be continuous. |
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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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5.1 | Number of sites anticipated in the EEA | 1 |
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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The end of trial is the date of database lock. This ensures all data is valid and participants numbers are correct. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |