Cariprazine for Bipolar depression

Inclusion criteria

• {"criterion_text":"- A diagnosis of bipolar disorder, type 1 or type 2.\n- Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI).\n- No start or dose increase of psychotropic medication (except for benzodiazepines and benzodiazepine-like drugs (zopiclone, zolpidem, and melatonin)) in the two weeks prior to inclusion.\n- No new start of formalized psychotherapy sessions, excluding psychoeducation, during the 4 weeks prior to inclusion.\n- Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization.\n- The duration of the current depressive episode must be between 4 and 52 weeks as judged by the investigator at the time of randomization.\n- Clinical uncertainty regarding which of the alternatives, cariprazine and lithium, would be the better choice in the specific case.\n- Female participants should be sterile or non-fertile or, in case of being fertile, they must have a negative pregnancy test AND use safe anticonception.\n- Signed document of informed consent."}

Exclusion criteria

• {"criterion_text":"- Prior or ongoing acute treatment of a depressive episode lasting > 14 days with either lithium or cariprazine as judged by the investigator.\n- Medical conditions like cancer, kidney failure, epilepsy, deep brain stimulation device, or other medical conditions interfering with study the outcome and safety as judged by investigator's discretion.\n- Current harmful use or dependency of alcohol or drugs according to DSM-5.\n- Known allergy to any of the substances in the study medication.\n- ECT within the current depressive episode.\n- A score of MAS > 6.\n- A diagnosis of dementia.\n- High risk of non-adherence at the investigator's discretion.\n- Not understanding the Danish language as judged by the investigator.\n- Psychiatric coercion in the form of forced admission or detainment OR sentence to forensic psychiatric care.\n- Presence of clinically relevant delusions, hallucinations or other psychotic symptoms as judged by the investigator.\n- Suicidality according to C-SSRS with a positive response to question 4 or 5 or upon investigator's discretion."}

Primary endpoints

• {"endpoint_text":"- investigate whether cariprazine is superior to lithium or vice versa in the acute treatment of patients with bipolar type 1 or 2 in a current depressive episode measured as change on the Hamilton Depression Scale, 6 item version, HDS-6.","definition_or_measurement_approach":"Measured as change on the Hamilton Depression Scale, 6 item version (HDS-6)."}

Secondary endpoints

• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: Hamilton Depression Scale, 17 item version, HDS-17. (Values 0- 52, higher scores mean a worse outcome).","definition_or_measurement_approach":"HDS-17 (0-52); higher scores indicate worse outcome; analysed as difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences (baseline to 8 weeks) in HDS-6 for the PP 8 population.","definition_or_measurement_approach":"Change in HDS-6 from baseline to 8 weeks in per-protocol 8 population; analysed as difference-in-differences."}
• {"endpoint_text":"- Between-groups difference in proportion of responders and remitters at week 4 and 8 in HDS-6 scores.","definition_or_measurement_approach":"Proportion of responders and remitters at weeks 4 and 8 using HDS-6; between-group comparisons."}
• {"endpoint_text":"- Between-groups difference in proportion of responders and remitters with response and remission defined by HDS-6 score without clinical relevant manic symptoms (MAS <7) at planned or premature endpoint.","definition_or_measurement_approach":"Response/remission defined by HDS-6 with MAS <7 (no clinically relevant manic symptoms); between-group proportions at planned/premature endpoint."}
• {"endpoint_text":"- Between-groups difference in the proportion of patients with 'acceptable wellbeing', defined as the subject reporting ≥50 on the WHO-5 questionnaire at endpoint. WHO-five Well-being Index, WHO-5","definition_or_measurement_approach":"WHO-5 score ≥50 at endpoint defines 'acceptable wellbeing'; between-group proportion comparison."}
• {"endpoint_text":"- Between-groups difference in the proportion of patients with 'acceptable wellbeing', defined as the subject reporting ≥50 on the WHO-5 questionnaire at endpoint. WHO-five Well-being Index, WHO-5.","definition_or_measurement_approach":"WHO-5 score ≥50 at endpoint; between-group comparison (duplicate entry in source)."}
• {"endpoint_text":"- Between-groups difference in \"(switch to mania or hypomania) / (response) -ratio\", defined as the number of subjects switching to mania or hypomania (as defined above) divided by the total number of responders, including those responders switching to mania.","definition_or_measurement_approach":"Ratio = (number switching to mania/hypomania) / (number of responders, including those who switched); between-group comparison."}
• {"endpoint_text":"- Between-group differences in reason for and time to all cause treatment discontinuation (lack of effect, lack of tolerability, lost to follow-up, or other cause).","definition_or_measurement_approach":"Time-to-event and categorical reasons for all-cause treatment discontinuation compared between groups."}
• {"endpoint_text":"- Between-group difference in treatment compliance. Treatment compliance is defined as the proportion of received treatments out of the planned until drop-out or end of study.","definition_or_measurement_approach":"Treatment compliance = proportion of received treatments out of planned until dropout or study end; between-group comparison."}
• {"endpoint_text":"- Between-group difference for the ITT population in reasons for premature discontinuation.","definition_or_measurement_approach":"Categorical comparison of reasons for premature discontinuation in ITT population between groups."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: MAS Bech-Rafaelsens Mania scale .(Values 0- 44, higher scores mean a worse outcome).","definition_or_measurement_approach":"MAS Bech-Rafaelsen Mania scale (0-44); higher worse; difference-in-differences analysis."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: MES Bech-Rafaelsens Melancholia scale, MES .(Values 0- 44, higher scores mean a worse outcome).","definition_or_measurement_approach":"MES Bech-Rafaelsen Melancholia scale (0-44); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: MADRS Montgomery-Aaberg Depression Rating Scale, MADRS .(Values 0- 60, higher scores mean a worse outcome).","definition_or_measurement_approach":"MADRS (0-60); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures:YMRS Young Mania Rating Scale, YMRS .(Values 0- 60, higher scores mean a worse outcome).","definition_or_measurement_approach":"YMRS (0-60); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures:ASRM-14 Altman Self-Rating Mania Scale-14, .(Values 0- 56, higher scores mean a worse outcome).","definition_or_measurement_approach":"ASRM-14 (0-56); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures:MDI Major Depression Inventory, MDI (Values 0- 58, higher scores mean a worse outcome).","definition_or_measurement_approach":"MDI (0-58); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: WHO-5 questionnaire.","definition_or_measurement_approach":"WHO-5 score change; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: SCIP Screen for Cognitive Impairment in Psychiatry, SCIP (Values 0- 64+, higher scores mean a better outcome).","definition_or_measurement_approach":"SCIP (0-64+); higher better; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: COBRA Cognitive complaints in bipolar disorder Ratings assessment, COBRA, (Values 0- 48, higher scores mean a worse outcome).","definition_or_measurement_approach":"COBRA (0-48); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: FAST Functioning Assessment Short Test, FAST (Values 0 - 72, higher scores mean a worse outcome).","definition_or_measurement_approach":"FAST (0-72); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures:PSQI PIttsburgh Sleep Quality Index, PSQI (Values 0 - 21, higher scores mean a worse outcome).","definition_or_measurement_approach":"PSQI (0-21); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: CGI-S Clinical Global Impression Scale - Severity, CGI-S (Values 1 -7, higher scores mean a worse outcome).","definition_or_measurement_approach":"CGI-S (1-7); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures:CGI-I Clinical Global Impression Scale - Global Improvement CGI- I (Values 1 -7, higher scores mean a worse outcome).","definition_or_measurement_approach":"CGI-I (1-7); difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: C-SSRS Columbia-Suicide Severity Rating Scale, C-SSRS (Values 1 - 5, higher scores mean a worse outcome).","definition_or_measurement_approach":"C-SSRS (1-5); higher worse; difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: accumulated benzodiazepine dose as diazepam equivalents (DSKP).","definition_or_measurement_approach":"Accumulated benzodiazepine dose (diazepam equivalents); difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: for time to all-causes discontinuation.","definition_or_measurement_approach":"Time to all-cause discontinuation analysed as difference-in-differences."}
• {"endpoint_text":"- Difference-in-differences for secondary continuous measures: all-causes study endpoint.","definition_or_measurement_approach":"All-cause study endpoint measured and analysed as difference-in-differences."}
• {"endpoint_text":"- Between-group difference for the ITT population in reasons for time to all cause discontinuation.","definition_or_measurement_approach":"Between-group comparison of reasons and time to all-cause discontinuation in ITT population."}
• {"endpoint_text":"- Between-group difference for the ITT population in reasons for treatment expectation.","definition_or_measurement_approach":"Between-group comparison of reasons for treatment expectation in ITT population."}
• {"endpoint_text":"- Between-group difference for the ITT population in reasons for adverse events.","definition_or_measurement_approach":"Between-group comparison of reasons for adverse events in ITT population."}
• {"endpoint_text":"- Between-group difference for the ITT population in reasons for serious adverse events.","definition_or_measurement_approach":"Between-group comparison of reasons for serious adverse events in ITT population."}

Denmark

Earliest CTIS Part Ii Submission Date

23-09-2024

Latest Decision Or Authorization Date

02-10-2024

Processing Time Days

9

Number Of Sites

2

Number Of Participants

122

Primary sponsor

Full Name

Aalborg University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Aalborg University Hospital","duties_or_roles":"1","organisation_type":"Hospital/Clinic/Other health care facility"}