Higher-Dose Maintenance With ERZOFRI 351 mg in Adults With Schizophrenia
SCHIZOPHRENIA 1 (Disorder)
What this study involves
The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.
- Study type
- Interventional
- Phase
- Phase 4
- Age range
- 18 years - 65 years
- Sex eligible
- All sexes
- Healthy volunteers
- Not accepted
- Participants
- 40 Estimated
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
This is a prospective, multicenter, open-label, single-arm study evaluating ERZOFRI (paliperidone palmitate) 351 mg administered every 4 weeks as maintenance treatment in approximately 40 adults with schizophrenia who experience symptom worsening before their next scheduled monthly injection despite receiving paliperidone palmitate 234 mg every 4 weeks.
Participants will receive ERZOFRI 351 mg on Day 1, Week 4, and Week 8 and will complete an end-of-study assessment at Week 12. The study will evaluate changes in clinical severity over 12 weeks and will also assess movement-related side effects and sexual functioning.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
Inclusion Criteria:
1. Adults aged 18-65 years with a DSM-5 diagnosis of schizophrenia.
2. Currently receiving monthly paliperidone palmitate long-acting injectable (INVEGA SUSTENNA or ERZOFRI) at a dose of 234 mg every 4 weeks (Q4W) for at least 3 consecutive months before Screening.
3. Clinician-documented symptom breakthrough, destabilization, or functional deterioration occurring before the scheduled 4-week injection interval during at least 2 of the 3 most recent monthly injection cycles (not necessarily consecutive). Documentation may include progress notes indicating symptom worsening in the final week before the next injection, unscheduled clinic or emergency department visits for psychiatric symptoms, as-needed medication use for breakthrough psychosis, or clinician judgment based on longitudinal care.
4. Documented prior tolerability to oral paliperidone or oral risperidone.
5. Clinical Global Impression-Severity (CGI-S) score ≥3 (mildly ill) and ≤6 (severely ill) at Baseline.
6. Able and willing to independently provide written informed consent.
Exclusion Criteria:
1. Known hypersensitivity to paliperidone, risperidone, or any ERZOFRI formulation excipient.
2. Renal impairment, defined as creatinine clearance (CrCl) \<50 mL/min.
3. Hemoglobin A1c (HbA1c) ≥7.0% at Screening.
4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 times the upper limit of normal (ULN) at Screening.
5. Body mass index (BMI) \>43 kg/m² at Screening.
6. QT interval corrected using Fridericia's formula (QTcF) \>450 milliseconds (ms) for males or \>470 ms for females at Screening. A QTcF ≥480 ms is exclusionary regardless of sex.
7. Other clinically significant electrocardiogram abnormalities, including serious ventricular arrhythmias, clinically significant conduction abnormalities, or evidence of unstable cardiovascular disease, as determined by the investigator.
8. Other metabolic abnormalities or medical conditions that, in the investigator's judgment, represent active, uncontrolled disease that could compromise participant safety or suitability for study participation.
9. Current or recent (within the past 30 days) participation in another interventional clinical trial.
10. Severe substance use disorder within the past 6 months, according to DSM-5 criteria.
11. Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to comply with protocol-specified contraception requirements throughout study participation and for 45 days following the final study injection.
12. History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia (TD) requiring treatment discontinuation.
13. Current use of strong CYP3A4 and/or P-glycoprotein (P-gp) inducers, including carbamazepine, rifampin, or St. John's Wort.
14. Imminent risk of harm to self or others, as assessed by the investigator.
Treatment, groups and participation
The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.
- Assignment
- Not applicable
- Masking
- No masking
ERZOFRI 351 mg Q4W
Participants will receive ERZOFRI 351 mg by intramuscular injection on Day 1, Week 4, and Week 8, followed by an end-of-study assessment at Week 12.
Drug: Paliperidone Palmitate
Paliperidone Palmitate DRUG
Paliperidone palmitate extended-release injectable suspension (ERZOFRI) 351 mg administered by intramuscular injection on Day 1, Week 4, and Week 8. The Day 1 injection will be administered in the deltoid muscle; subsequent injections may be administered in the deltoid or gluteal muscle.
What researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
Mean Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S) Score
Time frame: Baseline (Day 1) and Week 12
Change in clinician-rated CGI-S score from Baseline (Day 1) to Week 12. The CGI-S is a 7-point scale assessing overall severity of mental illness, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Negative changes from baseline indicate improvement.
Secondary measures
Patient Clinical Global Impression-Improvement (PCGI-I) Response
Time frame: Weeks 4, 8, and 12
Proportion of participants reporting a PCGI-I score ≤2 ("much improved" or "very much improved"). The PCGI-I is a 7-point patient-reported measure of perceived global improvement, ranging from 1 (very much improved) to 7 (very much worse). Lower scores indicate greater improvement.
Change From Baseline in Simpson-Angus Scale (SAS) Total Score
Time frame: Baseline, Week 4, Week 8, and Week 12
Change from baseline in total SAS score. The SAS is a 10-item clinician-rated scale assessing parkinsonian signs. Each item is scored from 0 (normal) to 4 (extreme), with total scores ranging from 0 to 40; higher scores indicate greater severity of parkinsonian symptoms.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Items 1-7 Total Score
Time frame: Baseline, Week 4, Week 8, and Week 12
Change from baseline in the total score for AIMS Items 1-7. The AIMS is a clinician-rated scale assessing involuntary movements involving the facial/oral regions, extremities, and trunk. Items 1-7 are each scored from 0 (none) to 4 (severe), with higher scores indicating greater severity of involuntary movements. The total score for Items 1-7 ranges from 0 to 28.
Correlation Between Serum Prolactin Concentration and Arizona Sexual Experience Scale (ASEX) Total Score
Time frame: Week 12
Correlation between serum prolactin concentration (ng/mL) and sexual dysfunction assessed using the Arizona Sexual Experience Scale (ASEX) at Week 12. The ASEX is a five-item questionnaire with total scores ranging from 5 to 30; higher scores indicate greater sexual dysfunction. The relationship will be evaluated using Pearson or Spearman correlation coefficients, as appropriate.
Clinical Global Impression-Improvement (CGI-I) Response
Time frame: Weeks 4, 8, and 12
Proportion of participants achieving a CGI-I score ≤2 ("much improved" or "very much improved"). The CGI-I is a 7-point clinician-rated scale assessing overall clinical improvement relative to baseline, ranging from 1 (very much improved) to 7 (very much worse). Lower scores indicate greater improvement.
Change From Baseline in Arizona Sexual Experience Scale (ASEX) Total Score
Time frame: Baseline, Weeks 4, 8, and 12
Change from baseline in ASEX total score at Weeks 4, 8, and 12. The ASEX is a five-item questionnaire assessing sexual functioning, with total scores ranging from 5 to 30. Higher scores indicate greater sexual dysfunction.
Other measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Day 1 through Week 12
Number and proportion of participants experiencing treatment-emergent adverse events during the study, with adverse event severity summarized.
Change From Screening to Week 12 in Serum Prolactin Concentration
Time frame: Screening and Week 12
Change in serum prolactin concentration (ng/mL) from Screening to Week 12 during treatment with ERZOFRI 351 mg Q4W.
Mean Change From Baseline in Fasting Glucose
Time frame: Baseline and Week 12
Change from baseline to Week 12 in fasting blood glucose concentration, measured in mg/dL.
Injection-Site Pain Severity Score
Time frame: Day 1, Weeks 4 and 8
Severity of injection-site pain following ERZOFRI administration, assessed by the investigator using an 11-point numerical rating scale ranging from 0 (no pain) to 10 (most severe pain). Higher scores indicate greater severity.
Mean Change From Baseline in QTcF Interval
Time frame: Baseline, Weeks 4, 8, and 12
Change from baseline in the QT interval corrected using Fridericia's formula (QTcF), measured in milliseconds (ms), as assessed by 12-lead electrocardiogram (ECG).
All-Cause Study Discontinuation
Time frame: Day 1 through Week 12
Number and proportion of participants who discontinue the study before Week 12, with reasons for discontinuation summarized.
Symptom Breakthrough Before the 4-Week Injection Interval
Time frame: Day 1 through Week 12
Proportion of participants experiencing symptom breakthrough before the scheduled 4-week injection interval during the study period, compared with their documented pre-enrollment rate of symptom breakthrough.
Number of Unscheduled Clinic Visits for Psychiatric Symptoms
Time frame: Day 1 through Week 12
Total number of unscheduled clinic visits related to psychiatric symptoms occurring during the 12-week study period.
Mean Change From Baseline in Body Weight
Time frame: Baseline and Week 12
Change from baseline to Week 12 in body weight, measured in kilograms (kg).
Mean Change From Baseline in Body Mass Index (BMI)
Time frame: Baseline and Week 12
Change from baseline to Week 12 in body mass index (BMI), calculated as body weight in kilograms divided by height in meters squared (kg/m²).
Mean Change From Baseline in Waist Circumference
Time frame: Baseline and Week 12
Change from baseline to Week 12 in waist circumference, measured in centimeters (cm).
Mean Change From Baseline in Total Cholesterol
Time frame: Baseline and Week 12
Change from baseline to Week 12 in serum total cholesterol concentration, measured in mg/dL.
Mean Change From Baseline in HDL Cholesterol
Time frame: Baseline and Week 12
Change from baseline to Week 12 in high-density lipoprotein (HDL) cholesterol concentration, measured in mg/dL.
Mean Change From Baseline in LDL Cholesterol
Time frame: Baseline and Week 12
Change from baseline to Week 12 in low-density lipoprotein (LDL) cholesterol concentration, measured in mg/dL.
Mean Change From Baseline in Triglycerides
Time frame: Baseline and Week 12
Change from baseline to Week 12 in serum triglyceride concentration, measured in mg/dL.
Injection-Site Swelling Severity Score
Time frame: Day 1, Weeks 4 and 8
Severity of injection-site swelling following ERZOFRI administration, assessed by the investigator using an 11-point numerical rating scale ranging from 0 (no swelling) to 10 (most severe swelling). Higher scores indicate greater severity.
Injection-Site Redness Severity Score
Time frame: Day 1, Weeks 4 and 8
Severity of injection-site redness following ERZOFRI administration, assessed by the investigator using an 11-point numerical rating scale ranging from 0 (no redness) to 10 (most severe redness). Higher scores indicate greater severity.
Number of Emergency Department Visits for Psychiatric Symptoms
Time frame: Day 1 through Week 12
Total number of emergency department visits related to psychiatric symptoms occurring during the 12-week study period.
Number of Psychiatric Hospitalizations
Time frame: Day 1 through Week 12
Total number of psychiatric hospitalizations occurring during the 12-week study period.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (3)
The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.
3 locations
ATP Clinical ResearchOrange, California, United StatesStatus unknown
Passageway Residences of Dade CountyMiami, Florida, United StatesStatus unknown
Pillar Clinical ResearchChicago, Illinois, United StatesStatus unknown
Study team and timeline
- Lead sponsor
- Alejandro Alva
- Study start
- 2026-12 Estimated
- Primary completion
- 2027-12 Estimated
- Study completion
- 2027-12 Estimated
- First posted
- Nov 10, 2026 Actual
- Last updated
- Nov 10, 2026 Actual
Official study contacts
Official study title
Exploratory Evaluation of ERZOFRI (Paliperidone Palmitate) 351 mg Q4W Maintenance in Higher-Need Patients With Schizophrenia: Clinical Global Improvement, Drug-Induced Parkinsonism, and Sexual Dysfunction Outcomes Over a 3-Month Treatment Period
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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.
Retrieved: Nov 12, 2026 · Last registry update: Nov 10, 2026