Clinical trial NCT06107803: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Negative Symptoms in Schizophrenia
Lead sponsor: Minerva Neurosciences
Sponsor class: INDUSTRY
First posted: 2023-10-30
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement
timeFrame: Overall - Change from Baseline to End of Study (Day 17)
measure: Barnes Akathisia Rating Scale (BARS)
timeFrame: Overall - Change from Baseline to End of Study (Day 17)
measure: Number of Subjects Who Experienced Suicidal Ideation or Behavior Events Per the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Overall - End of Study (Day 17)
Secondary outcomes:
measure: Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax)
timeFrame: Days 1 through 17
measure: Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax)
timeFrame: Days 1 through 17
measure: Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24)
timeFrame: Days 1 through 17
measure: Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf)
timeFrame: Days 1 through 17
measure: Plasma PK Parameter for Olanzapine Cmax
timeFrame: Treatment Phase 2 (Day 8 through Day 17)
measure: Plasma PK Parameter for Olanzapine Tmax
timeFrame: Treatment Phase 2 (Day 8 through Day 17)
measure: Plasma PK Parameter for Olanzapine AUC 0-24
timeFrame: Treatment Phase 2 (Day 8 through Day 17)
measure: Plasma PK Parameter for Olanzapine AUC Inf
timeFrame: Treatment Phase 2 (Day 8 through Day 17)
measure: Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax)
timeFrame: Days 1 through 17
measure: Pharmacokinetic Evaluation of Co-administration - AUC 0-24
timeFrame: Days 1 through 17
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Research, LLC
state: California
city: Gaithersburg
country: United States
facility: CBH Health, LLC
state: Maryland
city: Marlton
country: United States
facility: Hassman Research Institute
state: New Jersey
Study officials:
References: