Safety and efficacy of olanzapine treatment in psychosis: Effect of genetic and epigenetic factors – covariates of treatment response

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Masarykova Univerzita

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04]

Trial duration

24 Oct 2023 → 23 Sep 2025

Decision date (initial)

2023-05-04

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Masaryk University

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenomic, Efficacy, Pharmacokinetic, Pharmacogenetic, Therapy

The primary aim is to evaluate proportions (frequency) of gene polymorphisms in CYP1A2, MDR1, 5HT2A, 5HT2C, HDAC3 and HDAC4 genes in the study population of patients with schizophrenia.

Secondary objectives 1

1. The secondary aims are the evaluation of the effect of covariates (gene polymorphisms, CYP1A2 phenotype, cytosine methylation of 5HT2A receptor gene, levels of olanzapine and desmethylolanzapine in serum, smoking habits and co-medication) on the efficacy and safety (tolerability) of olanzapine treatment in the study population.

Conditions and MedDRA coding

Psychoses

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age 18‒60 years
2. Dg. F20 (schizophrenia) or F25 (schizoaffective disorders) according to ICD-10
3. Established treatment with olanzapine, or planned initiation of olanzapine treatment
4. Expressed the informed consent and will to co-operate
5. Women of childbearing potential can be included only if they are using at least an acceptable effective contraceptive measure (Chapter 8.10)

Exclusion criteria 5

1. Sui juris restriction or divestiture
2. Olanzapine or caffeine contraindication
3. Pregnancy, or planning to conceive, breastfeeding
4. Prior participation in any other trial involving investigational medication or medical devices within 14 days prior to the enrolment and during this trial
5. Other serious medical or psychiatric illness that is not adequately controlled and, in the investigator’s opinion, would not permit the subject to be managed according to the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency of gene polymorphisms of CYP1A2, MDR1, 5HT2A, 5HT2C, HDAC3 and HDAC4

Secondary endpoints 8

1. Cytosine methylation of 5HT2A
2. Metabolic phenotype of CYP1A2
3. Response rate: The treatment response is defined as 20% reduction in PANSS score (see Chapter 7.2) on day 14 or 30% reduction in PANSS score on day 28 compared to baseline score.
4. Remission rate: Remission is defined in compliance with the “Remission in Schizophrenia Working Group” as reduction of the severity of symptoms evaluated in items P1, P2, P3, G5, G9, N1, N4, N6 of PANSS scale to ≤ 3 degree; with respect to the study period, although the original recommended time factor (6 months) will not be included in the evaluation.
5. Time to reach the treatment response (i.e., 20% reduction in PANSS score).
6. Number of "drop-outs" (olanzapine treatment cessation) and their reasons.
7. Side effects assessment: UKU scale (see Chapter 8.3)
8. Treatment of the adverse effects of olanzapine – medication, doses, treatment duration, changes in olanzapine administration.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Masarykova Univerzita

Sponsor organisation

Masarykova Univerzita

Address

Zerotinovo Namesti 617/9, Brno-Mesto Brno-Mesto

City

Brno

Postcode

602 00

Country

Czechia

Scientific contact point

Organisation

Masarykova Univerzita

Contact name

Jan Juřica

Public contact point

Organisation

Masarykova Univerzita

Contact name

Regina Demlová

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 3 files

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

Application history

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