Negative Symptoms in SchizophreniaPhase 1NCT06107803
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
A Phase 1 study testing Roluperidone 64 mg and Olanzapine 10 MG in people with Negative Symptoms in Schizophrenia, run by Minerva Neurosciences at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Negative Symptoms in Schizophrenia
- What is being tested?
- Roluperidone 64 mg and Olanzapine 10 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Oct 2023to 12 Jan 2024
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
CBH Health, LLC
Gaithersburg, Maryland, 20877
Collaborative Neuroscience Research, LLC
Garden Grove, California, 92845
Hassman Research Institute
Marlton, New Jersey, 08053
About this study
Official title: A Phase 1b, In-Patient Study 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 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.
Read more
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
- Being tested
- Roluperidone 64 mg, Olanzapine 10 MG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Roluperidone 64 mgDrug
Also called MIN-101
64 mg/day oral
Olanzapine 10 MGDrug
10 mg/day oral
| Study group | Role | What they receive |
|---|---|---|
| Treatment Phase 1 | Experimental | Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7. Receives: Drug: Roluperidone 64 mg |
| Treatment Phase 2 | Experimental | Roluperidone 64 mg oral and olanzapine 10 mg oral administered at the same time daily for 10 days on Days 8-17. Receives: Drug: Roluperidone 64 mg; Drug: Olanzapine 10 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement
AIMS is a rating scale to measure tardive dyskinesia (TD). For the scoring, the AIMS scale has 14 items. The first 10 items (under categories of Facial and Oral Movements, Extremity Movements, Trunk Movements, and Global Judgements) are rated from 0 (none) to 4 (severe); the remaining 4 items (Dental Status) are rated "yes" and "no" and not counted. The analysis is limited to items 1 to 10, with each rated from 0 to 4. The total score is the sum of all 10 items and with values ranging from 0 to 40. Overall change from baseline to End of Study (Day 17) in AIMS was reported for the Safety Set. Higher scores imply worse outcome.
Measured: Overall - Change from Baseline to End of Study (Day 17)
Barnes Akathisia Rating Scale (BARS)
BARS is a multiple-choice questionnaire that clinicians may use to provide an assessment of akathisia. The clinician or rater is instructed to observe the subject while standing and while sitting, at least 2 minutes each (total of at least 4 minutes in total). There are 4 areas where the subject is to be evaluated, 1 of these is objective, 2 are subjective, and the final is a global assessment. The BARS scale has 3 items that are rated from 0 (absence/no distress) to 3 (most severe). The BARS rating scale is scored by summing the scales for Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness yielding a total score ranging from 0 to 9. The Total score, which has a possible range from 0-9, is reported. Higher scores imply worse outcome.
Measured: Overall - Change from Baseline to End of Study (Day 17)
Number of Subjects Who Experienced Suicidal Ideation or Behavior Events Per the Columbia Suicide Severity Rating Scale (C-SSRS)
C-SSRS is a measure to identify and assess individuals at risk for suicide. Questions are phrased for an interview format but can be completed as a self-report measure if needed. It measures 4 constructs: severity of ideation, intensity of ideation, behavior, and lethality. It includes "stem questions," which if endorsed, prompt additional follow-up questions to obtain more information. For the composite endpoint of suicidal ideation or behavior (1-10), the number and percent of subjects in the Overall Safety Set who experience any one of the ten suicidal ideation or behavior events at End of Study (Day 17).
Measured: Overall - End of Study (Day 17)
Secondary outcomes (10)
Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax)
Cmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Measured: Days 1 through 17
Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax)
Tmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Measured: Days 1 through 17
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24)
AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Measured: Days 1 through 17
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf)
AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Measured: Days 1 through 17
Plasma PK Parameter for Olanzapine Cmax
Cmax of olanzapine administered concomitantly with roluperidone
Measured: Treatment Phase 2 (Day 8 through Day 17)
Plasma PK Parameter for Olanzapine Tmax
Tmax of olanzapine administered concomitantly with roluperidone
Measured: Treatment Phase 2 (Day 8 through Day 17)
Plasma PK Parameter for Olanzapine AUC 0-24
AUC 0-24 olanzapine administered concomitantly with roluperidone
Measured: Treatment Phase 2 (Day 8 through Day 17)
Plasma PK Parameter for Olanzapine AUC Inf
AUC inf olanzapine administered concomitantly with roluperidone
Measured: Treatment Phase 2 (Day 8 through Day 17)
Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax)
Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for Cmax.
The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite.
Measured: Days 1 through 17
Pharmacokinetic Evaluation of Co-administration - AUC 0-24
Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for AUC 0-24.
The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite.
Measured: Days 1 through 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2023
- Study start13 Oct 2023
- Primary completion12 Jan 2024
- Study completion12 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Negative Symptoms in SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Minerva Neurosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06107803
- Sponsor's protocol ID
- MIN-101C18
- Status last verified
- Mar 2025
- First submitted
- 13 Oct 2023
- Last updated
- 26 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No