Esketamine nasal spray (Spravato) for the treatment of therapy-resistant bipolar depression. An open-label pilot trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Leiden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

1 Apr 2025 → ongoing

Decision date (initial)

2024-11-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The study is an open-label pilot study of esketamine nasal spray in patients with treatment-resistant bipolar depression to assess efficacy in global, but most importantly safety and tolerability. At the current stage of drug trials involving re-designation of esketamine nasal spray, this study design is the most appropriate as this may form the base towards a future randomized, placebo-controlled trial.

Conditions and MedDRA coding

Bipolar disorder- depressive episode

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Diagnosis of bipolar I or II disorder
2. Age between 18 and 75
3. MADRS scores above 18
4. Current episode of depression
5. Meeting the criteria of a current treatment resistant depression defined as a failure to respond to at least two different antidepressant or mood stabilizing agents during a sufficient amount of time at a sufficient dosage
6. Currently be on treatment with a mood stabilizer, but may not have been treated with more than five anti-depressant therapies for the current episode
7. Medication at a stable dosage for at least two weeks
8. Availability on Monday and Friday

Exclusion criteria 11

1. Known allergies against esketamine, or it's excipients
2. Previously been treated with esketamine or have been part of an esketamine trial
3. Unable to follow instructions or unable to make their own decisions regarding treatment
4. Known cardiovascular problems that could result in severe side effects due to a rise of blood pressure, for example: intracranial, abdominal or thoracic aneurysms and patients with recent cardiovascular events (less than six weeks ago), such as a myocardial infarction
5. Pregnancy as measured with a blood test at baseline
6. Suicidal to a point where closed admission is needed or the C-SSRS is four or higher
7. Psychosis (psychotic depression) as assessed with the MINI
8. Ketamine use disorder in their lifetime as assessed with the MINI
9. An active alcohol- or drug use disorder as assessed with the MINI
10. Using ketamine in a recreative manner at present, or with recreative use in the past 6 months
11. Women who are breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy as determined by response and remission rates: response is defined as a 50% or more reduction of the MADRS score. Remission is defined as a MADRS score that falls under ten.

Secondary endpoints 3

1. Safety will be determined by the number of side effects. The potential effect of conversion to mania will be measured by a YMRS of 20 or more points, indicating at least a mild mania. All other psychiatric side effects, such as psychosis and suicidality as well as somatic side effects will be meticulously monitored.
2. Tolarability will be determined by dropout rates during the whole study.
3. Relapse will be monitored and measured by: admission to a psychiatric hospital or ward due to depressive symptoms; a suicide attempt or admission to prevent suicide; an increase in depressive symptoms measured by the MADRS of >25% or above 22 points after initial response or remission following treatment.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Dr. Max de Leeuw

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Petra Herbschleb

Locations

1 EU/EEA country · 1 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 6 files

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

Application history

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