Efficacy and Safety of Cariprazine in the Treatment of Adolescent Participants (13 to 17 years of age) with Schizophrenia

2024-513194-44-00 Protocol RGH-MD-20 Therapeutic confirmatory (Phase III) Ended

Start 14 Dec 2021 · End 14 Apr 2026 · Status Ended · 2 EU/EEA countries · 3 sites · Protocol RGH-MD-20

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 257
Countries 2
Sites 3

Adolescent Patients (13 to 17 years of age) with Schizophrenia

To evaluate the efficacy of cariprazine 1.5 mg/d and cariprazine 4.5 mg/d compared to placebo in the treatment of adolescents (aged 13 to 17 years) with schizophrenia

Key facts

Sponsor
Gedeon Richter Plc.
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
14 Dec 2021 → 14 Apr 2026
Decision date (initial)
2024-08-06
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Gedeon Richter Plc

External identifiers

EU CT number
2024-513194-44-00
EudraCT number
2018-004006-26
ClinicalTrials.gov
NCT03817502

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Therapy, Efficacy

To evaluate the efficacy of cariprazine 1.5 mg/d and cariprazine 4.5 mg/d compared to placebo in the treatment of adolescents (aged 13 to 17 years) with schizophrenia

Secondary objectives 1

  1. To evaluate the safety and tolerability of cariprazine 1.5 mg/d and cariprazine 4.5 mg/d compared to placebo in the treatment of adolescents (aged 13 to 17 years) with schizophrenia

Conditions and MedDRA coding

Adolescent Patients (13 to 17 years of age) with Schizophrenia

VersionLevelCodeTermSystem organ class
20.0 PT 10039626 Schizophrenia 100000004873

Regulatory references

Scientific advice from competent authorities
European Medicines Agency
EMA paediatric investigation plan (PIP)
EMEA-001652-PIP01-14
Plan to share IPD
No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Inpatients or outpatients, 13 to 17 years of age, inclusive, at the time of obtaining the informed consent and assent
  2. DSM-5 primary diagnosis of schizophrenia
  3. Schizophrenia diagnosis confirmed by the K-SADS-PL administered at screening (Visit 1) by a trained clinician.
  4. PANSS score ≥ 70 and a score of ≥ 4 (moderate) on 2 or more of the 5 items on the positive subscale of the PANSS (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, suspiciousness/persecution), at screening (Visit 1) and baseline (Visit 2).
  5. CGI-S scale score of ≥ 4 (moderately ill) at screening (Visit 1) and baseline (Visit 2)

Exclusion criteria 3

  1. Current diagnosis of bipolar disorder, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder due to another medical condition
  2. Diagnosis of intellectual disability (IQ < 70)
  3. Participant has a history of meeting DSM-5 diagnosis for any substance-related disorder (except caffeine- and tobacco-related) within the 3 months before Visit 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Primary efficacy endpoint: Change from baseline to Week 6 on the PANSS total score

Secondary endpoints 1

  1. Comparison of AEs, clinical laboratory measures, vital signs, ECG, C-SSRS, CDSS, AIMS, BARS, SAS, UKU, menstrual cycle assessment, physical examination, and Tanner staging in cariprazine exposed participants versus placebo exposed participants

Investigational products

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

Test 4

Reagila 1.5 mg hard capsules

PRD5286020 · Product

Active substance
Cariprazine
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
1.5 mg milligram(s)
Max total dose
60 mg milligram(s)
Max treatment duration
6 Week(s)
Authorisation status
Authorised
ATC code
N05AX15 — -
Marketing authorisation
EU/1/17/1209/001
MA holder
GEDEON RICHTER PLC.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cariprazine 0.5 mg capsules, hard

PRD4515241 · Product

Active substance
Cariprazine Hydrochloride
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
1.5 mg milligram(s)
Max total dose
60 mg milligram(s)
Max treatment duration
6 Week(s)
Authorisation status
Not Authorised
ATC code
N05AX15 — -
MA holder
GEDEON RICHTER PLC.
Paediatric formulation
No
Orphan designation
No

Reagila 4.5 mg hard capsules

PRD5286546 · Product

Active substance
Cariprazine
Substance synonyms
RGH-188
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
4.5 mg milligram(s)
Max total dose
160.5 mg milligram(s)
Max treatment duration
6 Week(s)
Authorisation status
Authorised
ATC code
N05AX15 — -
Marketing authorisation
EU/1/17/1209/021
MA holder
GEDEON RICHTER PLC.
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Reagila 3 mg hard capsules

PRD5286518 · Product

Active substance
Cariprazine
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
4.5 mg milligram(s)
Max total dose
160.5 mg milligram(s)
Max treatment duration
6 Week(s)
Authorisation status
Authorised
ATC code
N05AX15 — -
Marketing authorisation
EU/1/17/1209/011
MA holder
GEDEON RICHTER PLC.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

For the purpose of the clinical study a placebo formulation was prepared using the same white hard gelatine capsule shell.

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gedeon Richter Plc.

2 Total trials 1 Recruiting 1 Ended
Commercial
Sponsor organisation
Gedeon Richter Plc.
Address
Gyomroi Ut 19-21
City
Budapest X
Postcode
1103
Country
Hungary

Scientific contact point

Organisation
Gedeon Richter Plc.
Contact name
MedicalInformationScientificService

Public contact point

Organisation
Gedeon Richter Plc.
Contact name
MedicalInformationScientificService

Third parties 8

OrganisationCity, countryDuties
Premier Research Group Limited
ORG-100009052
 Reading, United Kingdom Interactive response technologies (IRT)
Medidata Solutions Inc.
ORG-100016256
 New York, United States E-data capture
eResearchTechnology GmbH
ORG-100044103
 Estenfeld, Germany Other
Syneos Health Romania S.R.L.
ORG-100051180
 Bucharest, Romania On site monitoring, Code 5
Everest Clinical Research Corporation
ORG-100041734
 Markham, Canada Other
Labcorp Central Laboratory Services SARL
ORG-100011524
 Meyrin, Switzerland Other, Laboratory analysis
Signant Health Global LLC
ORG-100040604
 Blue Bell, United States Other
Catalent Germany Schorndorf GmbH
ORG-100011845
 Schorndorf, Germany Code 14

Locations

2 EU/EEA countries · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
Bulgaria Ended 19 2
Romania Ended 23 1
Rest of world
Mexico, Colombia, Russian Federation, Serbia
 — 215 —

Investigational sites

Bulgaria

2 sites · Ended
Multiprofile Hospital For Active Treatment - Targovishte AD
Department of Psychiatry, West District, Syuren Blvd 1, Targovishte
Alexandrovska University Hospital
Clinic of Child Psychiatry “Saint Nikolas”, Georgy Sofiiski Str 1, 1431, Sofia

Romania

1 site · Ended
Spitalul Clinic De Urgenta Pentru Copii Louis Turcanu Timisoara
Pediatric Psychiatry, Strada Corbului Nr 7, 300239, Timisoara

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Bulgaria 2021-12-14 2021-12-14 2026-02-26
Romania 2021-12-14 2022-07-28 2026-02-26

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Temporary halt TH-124705

Halt date
2026-02-26
Member states concerned
Romania
Publication date
2026-03-23
Reason
Medicinal Product related
Benefit-risk balance changed
No
Treatment stopped
No

Temporary halt TH-124703

Halt date
2026-02-26
Member states concerned
Bulgaria
Publication date
2026-03-23
Reason
Medicinal Product related
Benefit-risk balance changed
No
Treatment stopped
No

Results and documents

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

Documents 36 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-513194-44-00_redacted 4.0
Protocol (for publication) D1_Protocol_2024-513194-44-00_SoC 3.0
Protocol (for publication) D4_Subject Questionnaire__CSGQ Baseline_RO 1.0
Protocol (for publication) D4_Subject Questionnaire_CGSQ SLV_RO 1.0
Protocol (for publication) D4_Subject Questionnaire_CGSQ_Baseline_BG 1.0
Protocol (for publication) D4_Subject Questionnaire_CGSQ_Baseline_EN 1.0
Protocol (for publication) D4_Subject Questionnaire_CGSQ_SLV_BG 1.0
Protocol (for publication) D4_Subject Questionnaire_CGSQ_SLV_EN 1.0
Protocol (for publication) D4_Subject Questionnaire_PQ_LES_Q_RO 1.0
Protocol (for publication) D4_Subject Questionnaire_PQ-LES-Q_BG 1.0
Protocol (for publication) D4_Subject Questionnaire_PQ-LES-Q_EN 2.0
Recruitment arrangements (for publication) K1_Blank document N/A
Recruitment arrangements (for publication) K1_Recruitment arrangements 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1.0
Recruitment arrangements (for publication) K2_Recruitment material_Dr_to Dr_letter 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Dr_to Dr_letter_BG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Dr_to Dr_letter_ENG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Dr_to parent letter 2.1
Recruitment arrangements (for publication) K2_Recruitment material_Dr_to parent letter_BG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Dr_to parent letter_ENG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Flyer 1.0
Recruitment arrangements (for publication) K2_Recruitment material_IC flipchart 2.1
Recruitment arrangements (for publication) K2_Recruitment material_IC flipchart_BG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_IC flipchart_ENG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Participant recruitment brochure 1.0
Recruitment arrangements (for publication) K2_Recruitment material_Participant recruitment brochure_BG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Participant recruitment brochure_ENG 2.0
Recruitment arrangements (for publication) K2_Recruitment material_Poster 1.0
Subject information and informed consent form (for publication) L1_Placeholder_for publication N/A
Subject information and informed consent form (for publication) L2_ Other subject information material_Emergency Card_BG 2.0
Subject information and informed consent form (for publication) L2_ Other subject information material_Emergency Card_EN 2.0
Subject information and informed consent form (for publication) L2_ Other subject information material_Emergency Card_ENG 2.0
Subject information and informed consent form (for publication) L2_ Other subject information material_Emergency Card_RO 2.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_BG 3.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EN 3.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_RO 3

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-06-17 Romania Acceptable
2024-07-25
 2024-07-30
2 NON SUBSTANTIAL MODIFICATION NSM-1 2024-10-22 Acceptable
2024-07-25
 2024-10-22
3 NON SUBSTANTIAL MODIFICATION NSM-2 2025-02-24 Romania Acceptable
2024-07-25
 2025-02-24
4 SUBSTANTIAL MODIFICATION SM-1 2025-08-22 Romania Acceptable
2025-11-10
 2025-11-14
5 NON SUBSTANTIAL MODIFICATION NSM-3 2026-01-16 Romania Acceptable
2025-11-10
 2026-01-16