E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Form of mental illness where patients experience major depressive episodes and at least one hypomania episode. |
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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 | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10026753 |
E.1.2 | Term | Manic and bipolar mood disorders and disturbances |
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 determine the onset and 7-day durability of anti-depressive effects of a single-day individualized dosing regimen of 6 mg, 12 mg and 18 mg of GH001 in patients with bipolar II disorder and a current major depressive episode. |
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E.2.2 | Secondary objectives of the trial |
• To determine: o the safety and tolerability o the intensity and duration of the psychoactive effects (PsE) o the impact on cognitive outcomes.
of a single-day individualized dosing regimen of 6 mg, 12 mg and 18 mg of GH001 in patients with bipolar II disorder and a current major depressive episode.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Is male or female and in the age range between 18 and 64 years (inclusive) at screening; • Meets the trial criteria for bipolar II disorder and is experiencing a major depressive episode: • Meets the DSM-5 diagnostic criteria for bipolar II disorder with a current major depressive disorder episode confirmed by the Mini-International Neuropsychiatric Interview (MINI) v7.0.2 • Has a Montgomery–Åsberg Depression Rating Scale (MADRS) total score of ≥ 24 at screening and pre-dose on Day 0 • Has a Young Mania Rating Scale (YMRS) total score ≤ 8 at screening and prior to first dose on Day 0; • Agrees to keep any psychotherapy unchanged, and not initiate any new psychoactive medications during the trial; • Male patients must use prophylactic contraception (i.e., condom with spermicide or abstinence) and must not donate sperm for 30 days after GH001 dosing;
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E.4 | Principal exclusion criteria |
• Has bipolar II disorder with rapid cycling (four or more episodes of hypomania or depressive episodes in previous 12-month period); • Has, based on history, psychiatric assessment, and evaluation of the MINI, a current or prior diagnosis of bipolar I disorder, a manic episode, a psychotic disorder, major depressive disorder (MDD) or other mood disorder with psychotic features, obsessive compulsive disorder, PTSD, autism spectrum disorder, borderline personality disorder, clinically significant intellectual disability or any other psychiatric comorbidity that renders the patient unsuitable for the trial according to the investigator’s judgment; • Has one or more first or second degree relatives with a current or previously diagnosed psychotic disorder or MDD with psychotic features; • Is in the judgment of a trial psychiatrist or registered psychologist, at significant risk for suicide based on history, psychiatric assessment, and evaluation of suicidal ideation and suicidal behaviour based on the C-SSRS; • Has had an inadequate response to an adequate course of electroconvulsive therapy, vagal nerve stimulation, repetitive transcranial magnetic or electrical stimulation, or deep brain stimulation in the current episode of depression as assessed using the ATHF-SF; • Female patient who has a positive pregnancy test at screening or on the pre-test day (Day -1), is pregnant or lactating, or plans to become pregnant during the course of the trial and up to 30 days after GH001 dosing; • Patients with DSM-5 drug or alcohol use disorder within 6 months prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
•The anti-depressive effects of GH001 evaluated by: o Change from baseline in MADRS
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Prior to first dose on Day 0; • Day 7. |
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E.5.2 | Secondary end point(s) |
• The anti-depressive effects of GH001 evaluated by: • The proportion of patients in remission (MADRS ≤10); •Change from baseline in MADRS assessed; • The proportion of responders (≥50% reduction from baseline in MADRS total score); • Change from baseline in Clinical Global Impression – Bipolar scale (CGI-BP); • Change from baseline in Bipolar Depression Rating Scale (BDRS); • The safety and tolerability of GH001 evaluated by: • Reporting of Treatment Emergent Adverse Events (TEAEs); • Clinically significant changes from baseline in ECG, vital signs, safety laboratory assessments, peak flow respirometry; • Assessment of sedation (Modified Observer'’s Assessment of Alertness and Sedation scale [MOAA/S]); • The incidence of AEs of mania or hypomania (as assessed using the DSM-5 criteria for mania/hypomania); • Change from baseline in YMRS; • Change from baseline in Clinician Administered Dissociative States Scale (CADSS); • Assessment of patient discharge readiness using the Clinical Global Assessment of Discharge Readiness (CGADR); • Change from baseline in Brief Psychiatric Rating Scale (BPRS); • Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS); The PsE experienced by the patients when the PsE has subsided: • PsE assessment using the Peak Experience (PE) Scale to assess the achievement of a PE (PE scale total score ≥75); • Challenging Experience Questionnaire (CEQ); • Mystical Experience Questionnaire (MEQ-30); • Duration of the PsEs defined as the time from study drug dosing to the time when the PsE have subsided; The impact on cognitive outcomes as evaluated by: • Psychomotor Vigilance Task; • Auditory Verbal Learning Test; • Spatial Working Memory Task; • Digit Symbol Substitution Task.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• 2 hours after the final study drug dosing on Day 0, and at Day 1 and Day 7; • 2 hours after the final study drug dosing on Day 0, and at Day 1; • at 2 hours after the final study drug dosing on Day 0, and at Day 1 and Day 7; • Day 0, Day 1 and Day 7; • Day 0, Day 1 and Day 7; • from first dosing to Day 7; • Day-1, Day 0, Day 1 and Day 7; • Day 0; • Day 0, Day 1 and Day 7; • Day 0, Day 1 and Day 7; • Day 0 and at Day 1 and Day 7; • on Day 0; • Day-1, Day 0, Day 1 and Day 7; • Screening, Day 0, Day 1 and Week 1; • immediately after each dosing; • Day 0; • Day 0; • Day 0; • Day-1, Day 0 and Day 7; • Day-1, Day 0 and Day 7; • Day-1, Day 0 and Day 7; • Day-1, Day 0 and Day 7; |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open-label, non-randomized, single arm |
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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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |