Phase 1
Completed N=17
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
Negative Symptoms in Schizophrenia
Source: ClinicalTrials.gov NCT06107803 ↗
Enrolled (actual)
17
Serious AEs
3.1%
Results posted
Mar 2025
Primary outcomePrimary: Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement — 0.0 score on a scale
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement |
0.0 | — |
| PRIMARY Barnes Akathisia Rating Scale (BARS) |
0.0 | — |
| PRIMARY Number of Subjects Who Experienced Suicidal Ideation or Behavior Events Per the Columbia Suicide Severity Rating Scale (C-SSRS) |
— | — |
| SECONDARY Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) |
32.5; 5.00; 43.6; 7.98; 67.7; 12.2 | — |
| SECONDARY Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) |
9.74; 16.2; 7.47; 9.60; 6.20; 8.76 | — |
| SECONDARY Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) |
391; 52.3; 507; 135; 720; 203 | — |
| SECONDARY Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) |
338; 60.7; 495; 168; 883; 263 | — |
| SECONDARY Plasma PK Parameter for Olanzapine Cmax |
35.6 | — |
| SECONDARY Plasma PK Parameter for Olanzapine Tmax |
4.11 | — |
| SECONDARY Plasma PK Parameter for Olanzapine AUC 0-24 |
587 | — |
| SECONDARY Plasma PK Parameter for Olanzapine AUC Inf |
719 | — |
| SECONDARY Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax) |
39.8; 62.2; 5.96; 8.54 | — |
| SECONDARY Pharmacokinetic Evaluation of Co-administration - AUC 0-24 |
451; 656; 95.7; 135 | — |
Eligibility Criteria
Inclusion Criteria
- Provided informed consent
- Body mass index (BMI) 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 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
Data sourced from ClinicalTrials.gov (NCT06107803). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.