A Phase 2 Clinical Trial of GH001 in Patients with Bipolar II Disorder and a Current Major Depressive Episode

Phase 1

• Conditions: Bipolar II Disorder; MedDRA version: 26.1Level: HLGTClassification code 10026753Term: Manic and bipolar mood disorders and disturbancesSystem Organ Class: 10037175 - Psychiatric disorders; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2021-006861-39-DE
• Lead Sponsor: GH Research Ireland Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-08
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

4. Has a body mass index (BMI) in the range of 18.5 and 40 kg/m2 (inclusive) at screening.
5. Meets the trial criteria for bipolar II disorder and is experiencing a major depressive episode, as assessed by a trial psychiatrist or registered clinical psychologist:
-Meets the DSM-5 diagnostic criteria for bipolar II disorder with a current major depressive episode confirmed by the Mini-International Neuropsychiatric Interview (MINI) v7.0.2 -Has a Montgomery-Asberg Depression Rating Scale (MADRS) total score of = 24 at screening and prior to first dose on Day 0
8.Female patients must be either surgically sterile (hysterectomy, tubal ligation, or bilateral oophorectomy) or postmenopausal with amenorrhea for the last 2 years or remain completely abstinent (complete avoidance of heterosexual intercourse) or use a highly effective (failure rate <1%) medically accepted contraceptive method, including, but not limited to, hormone contraceptives that inhibit ovulation, intrauterine device (including hormone-releasing intrauterine device/systems) for 30 days before and 90 days after GH001 dosing and must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the pre-test day (Day -1).
10.Is able to inhale 3 liters of air from the test balloon within a single breath at screening, on the pre-test day (Day -1) and prior to first dose (Day 0). An incentive spirometer will be given to patients following screening. They will be encouraged to practice deep inhalations prior to the first dose on the test day (Day 0). Patients failing the test inhalation at screening may have the test inhalations repeated within 14 days of the original screening date.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

2. 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, post-traumatic stress disorder (PTSD), autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual disability, or any other psychiatric comorbidity that renders the patient unsuitable for the trial according to the investigator’s judgment.
3. Has one or more first degree relatives with a current or previously diagnosed psychotic disorder, bipolar I disorder, or MDD with psychotic features.
4. Has significant suicide risk as defined by:
(a) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, during the screening period, or at Baseline; or
(b) suicidal behaviors within the past year; or
(c) clinical assessment of significant suicidal risk during clinical interview; or
(d) non-suicidal self-injury within the past year.
6. Has taken anti-depressive medication e.g., a selective serotonin reuptake inhibitor (SSRI) such as paroxetine, fluoxetine (including in combination with olanzapine) or citalopram, a serotonin and norepinephrine reuptake inhibitor (SNRI) such as venlafaxine or duloxetine, a tricyclic antidepressant (TCA) such as amitriptyline or imipramine, an antipsychotic such as quetiapine, an atypical antidepressant such as bupropion or vortioxetine, or an N-methyl-D-aspartate (NMDA) receptor antagonist such as esketamine, within 7 days or 5 half-lives (whichever is longer) prior to dosing (exception: within the last 5 weeks in the case of fluoxetine).
Patients who at screening are on such medication and are willing to discontinue and observe a wash-out period of 7 days or 5 half-lives (whichever is longer) prior to GH001 dosing (5 weeks for fluoxetine), can still be included, but the wash-out must be implemented, completed and documented before study drug administration. Gradual dose reduction before discontinuation and wash-out should be performed as per the investigator’s judgement and applicable medical guidelines.
To ascertain patient safety during the potential taper and washout of anti-depressive medication, patients undergoing such taper and washout will be contacted weekly by the site.
8. Is taking mood stabilizer therapy other than lamotrigine at screening or is, by the investigator, considered to be in the need of mood stabilizer treatment other than lamotrigine during the study.
A period of at least 6 months without receipt of Lithium or Valproate and without an occurrence of a hypomanic episode is required prior to dosing.
A period of at least 2 weeks or 5 half-lives (whichever is longer) without receipt of atypical anti-psychotics (e.g., aripiprazole, olanzapine, risperidone) and without an occurrence of a hypomanic episode is required prior to dosing.
18.Has any current or past clinically significant condition (e.g., severe infection, severe pulmonary disease, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, severe hepatic or renal failure, severe brain disorder (including seizure disorder, stroke, dementia, degenerative neurologic diseases, meningitis, encephalitis, and head injury with loss of consciousness) that may interfere with the interpretation of t

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the onset and 7-day<br>durability of anti-depressive effects of a single-day IDR of 6 mg, 12 mg and 18 mg of GH001 in patients with bipolar II disorder and a current major episode of depression.;Secondary Objective: •To determine:<br>othe effect on depressive symptoms and global clinical status;<br>othe safety and tolerability;<br>othe intensity and duration of the psychoactive effects (PsE);<br>othe impact on sleep quality;<br>othe impact on cognitive outcomes<br><br><br>Of a single-day IDR of 6 mg, 12 mg and 18 mg of GH001 in patients with bipolar II disorder and a current major episode of depression.<br>;Primary end point(s): •The anti-depressive effects of GH001 evaluated by:<br>oChange from baseline in MADRS <br><br>;Timepoint(s) of evaluation of this end point: • Prior to first dose on Day 0;<br>• Day 7.