Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aalborg University Hospital

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

13 Dec 2022 → ongoing

Decision date (initial)

2024-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517170-20-01

EudraCT number

2021-006706-69

ClinicalTrials.gov

NCT05913947

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary aim is to 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.

Conditions and MedDRA coding

Depressive episode in bipolar disorder

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. A diagnosis of bipolar disorder, type 1 or type 2.
2. Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI).
3. 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.
4. No new start of formalized psychotherapy sessions, excluding psychoeducation, during the 4 weeks prior to inclusion.
5. Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization.
6. The duration of the current depressive episode must be between 4 and 52 weeks as judged by the investigator at the time of randomization.
7. Clinical uncertainty regarding which of the alternatives, cariprazine and lithium, would be the better choice in the specific case.
8. 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.
9. Signed document of informed consent.

Exclusion criteria 12

1. Prior or ongoing acute treatment of a depressive episode lasting > 14 days with either lithium or cariprazine as judged by the investigator.
2. ECT within the current depressive episode.
3. A score of MAS > 6.
4. A diagnosis of dementia.
5. High risk of non-adherence at the investigator's discretion.
6. Not understanding the Danish language as judged by the investigator.
7. Psychiatric coercion in the form of forced admission or detainment OR sentence to forensic psychiatric care.
8. Presence of clinically relevant delusions, hallucinations or other psychotic symptoms as judged by the investigator.
9. Suicidality according to C-SSRS with a positive response to question 4 or 5 or upon investigator's discretion.
10. 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.
11. Current harmful use or dependency of alcohol or drugs according to DSM-5.
12. Known allergy to any of the substances in the study medication.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 31

1. Difference-in-differences for secondary continuous measures: Hamilton Depression Scale, 17 item version, HDS-17. (Values 0- 52, higher scores mean a worse outcome).
2. Difference-in-differences (baseline to 8 weeks) in HDS-6 for the PP 8 population.
3. Between-groups difference in proportion of responders and remitters at week 4 and 8 in HDS-6 scores.
4. 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.
5. 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
6. 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.
7. 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.
8. 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).
9. 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.
10. Between-group difference for the ITT population in reasons for premature discontinuation.
11. Difference-in-differences for secondary continuous measures: MAS Bech-Rafaelsens Mania scale .(Values 0- 44, higher scores mean a worse outcome).
12. Difference-in-differences for secondary continuous measures: MES Bech-Rafaelsens Melancholia scale, MES .(Values 0- 44, higher scores mean a worse outcome).
13. Difference-in-differences for secondary continuous measures: MADRS Montgomery-Aaberg Depression Rating Scale, MADRS .(Values 0- 60, higher scores mean a worse outcome).
14. Difference-in-differences for secondary continuous measures:YMRS Young Mania Rating Scale, YMRS .(Values 0- 60, higher scores mean a worse outcome).
15. Difference-in-differences for secondary continuous measures:ASRM-14 Altman Self-Rating Mania Scale-14, .(Values 0- 56, higher scores mean a worse outcome).
16. Difference-in-differences for secondary continuous measures:MDI Major Depression Inventory, MDI (Values 0- 58, higher scores mean a worse outcome).
17. Difference-in-differences for secondary continuous measures: WHO-5 questionnaire.
18. Difference-in-differences for secondary continuous measures: SCIP Screen for Cognitive Impairment in Psychiatry, SCIP (Values 0- 64+, higher scores mean a better outcome).
19. 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).
20. Difference-in-differences for secondary continuous measures: FAST Functioning Assessment Short Test, FAST (Values 0 - 72, higher scores mean a worse outcome).
21. Difference-in-differences for secondary continuous measures:PSQI PIttsburgh Sleep Quality Index, PSQI (Values 0 - 21, higher scores mean a worse outcome).
22. 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).
23. 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).
24. 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).
25. Difference-in-differences for secondary continuous measures: accumulated benzodiazepine dose as diazepam equivalents (DSKP).
26. Difference-in-differences for secondary continuous measures: for time to all-causes discontinuation.
27. Difference-in-differences for secondary continuous measures: all-causes study endpoint.
28. Between-group difference for the ITT population in reasons for time to all cause discontinuation.
29. Between-group difference for the ITT population in reasons for treatment expectation.
30. Between-group difference for the ITT population in reasons for adverse events.
31. Between-group difference for the ITT population in reasons for serious adverse events.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aalborg University Hospital

Sponsor organisation

Aalborg University Hospital

Address

Moelleparkvej 10

City

Aalborg

Postcode

9000

Country

Denmark

Scientific contact point

Organisation

Aalborg University Hospital

Contact name

Renè Ernst Nielsen

Public contact point

Organisation

Aalborg University Hospital

Contact name

Renè Ernst Nielsen

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications