A Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Co-Administration of Roluperidone and Olanzapine in Adult Subjects With Moderate to Severe Negative Symptoms of Schizophrenia

NCT ID: NCT06107803

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-13
• Study Completion Date: 2024-01-12

Brief Summary

The goal of this clinical trial is to evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of the Co-Administration of Roluperidone and Olanzapine in Adult Subjects with Moderate to Severe Negative Symptoms of Schizophrenia.

The main question this clinical trial aims to answer are the pharmacodynamic and pharmacokinetic effects and safety of the concomitant therapy of Roluperidone with an established and widely used antipsychotic, such as olanzapine in order to provide further guidance to clinical practitioners that may prescribe off-label use of these drugs concomitantly in clinical practice.

Eligible Participants will undergo the following study phases in the clinic:

• Screening Phase: Between 2 and up to 28 days during which study eligibility will be established and subjects receiving psychotropics will be washed out. Subjects will remain inpatient at the clinical site at least through the end of Treatment Phase 2.
• Treatment Phase 1: After the Baseline Visit, Roluperidone 64 mg/day will be administered as a monotherapy for 7 days (Days 1-7).
• Treatment Phase 2: Concomitant administration of Olanzapine 10 mg/day and Roluperidone 64 mg/day for 10 days, starting on Day 8 (Days 8-17). Subjects may be discharged from the clinic at least 48 hours after the last administration of the study drugs and after the collection of the last plasma sample; however, the inpatient period may be extended at the discretion of the investigator.

End of Study (EOS): Will take place at least 14 days after the last dose of the study.

Conditions

Negative Symptoms in Schizophrenia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Phase 1

Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7.

Group Type: EXPERIMENTAL

Roluperidone 64 mg

Intervention Type: DRUG

64 mg/day oral

Treatment Phase 2

Roluperidone 64 mg oral and olanzapine 10 mg oral administered at the same time daily for 10 days on Days 8-17.

Group Type: EXPERIMENTAL

Roluperidone 64 mg

Intervention Type: DRUG

64 mg/day oral

Olanzapine 10 MG

Intervention Type: DRUG

10 mg/day oral

Interventions

Roluperidone 64 mg

64 mg/day oral

Intervention Type: DRUG

Olanzapine 10 MG

10 mg/day oral

Intervention Type: DRUG

Other Intervention Names

MIN-101

Eligibility Criteria

Inclusion Criteria

• Provided informed consent
• Body mass index (BMI) < 35 kg/m2
• Meets the diagnostic criteria for schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), as established by a full psychiatric interview in conjunction with the Mini International Neuropsychiatric Interview (MINI)
• Documented diagnosis of schizophrenia for at least 1 year before screening
• Stable in terms of both positive and negative symptoms of schizophrenia over the last 3 months
• Score of > 20 on the PANSS original negative symptoms subscale (Sum of N1+N2+N3+N4+N5+N6+N7) at Screening and Baseline (Day -1) AND < 4 points absolute difference between the 2 visits
• Discontinued psychotropic medications without risk to their clinical status or safety by Baseline
• Female subject, if not of childbearing potential, must be a woman who is post-menopausal or permanently sterilized
• Female subject, if of childbearing potential, must test negative for pregnancy and must be using a double barrier contraceptive method
• Must be normal metabolizer for P450 CYP 2D6, defined as a subject that has at least one functional allele (eg, *1, *2 or *35), as determined by study-specific genotyping test before the first drug dose is administered
• Has a caregiver or family member or health care personnel who can provide information towards assessment and support the subject in terms of compliance with the protocol

Exclusion Criteria

• Current major depressive disorder, bipolar disorder, panic disorder, obsessive compulsive disorder, or intellectual disability (intellectual developmental disorder diagnosed by age 14)
• PANSS item score of > 4 on:

• P4 Excitement/Hyperactivity
• P6 Suspiciousness/persecution
• P7 Hostility
• G8 Uncooperativeness
• G14 Poor impulse control
• CDSS total score > 6
• Score of ≥ 2 on any 2 of items 1, 2, or 3, or a score of ≥ 3 on item 4 of the Barnes Akathisia Rating Scale (BARS)
• Has had electroconvulsive therapy (ECT), vagal nerve stimulation (VNS), or repetitive trans-cranial magnetic stimulation (r-TMS) within the 6 months prior to the Screening visit or who are scheduled for ECT, VNS, or r-TMS at any time during the study
• Positive urine drug screen for drugs of abuse
• Currently taking proton pump inhibitors (PPI)
• Current systemic infection (eg, Hepatitis B, Hepatitis C, human immunodeficiency virus [HIV], tuberculosis)
• Requires or may require concomitant treatment with any other medication likely to increase QT interval
• Requires medication inhibiting CYP2D6
• Safety laboratory results show one or more of the following: potassium <3.4 mmol/L, or calcium <2.07 mmol/L, or magnesium <0.70 mmol/L

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Minerva Neurosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Collaborative Neuroscience Research, LLC

Garden Grove, California, United States

CBH Health, LLC

Gaithersburg, Maryland, United States

Hassman Research Institute

Marlton, New Jersey, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MIN-101C18

Identifier Type: -

Identifier Source: org_study_id