Steady-state Bioequivalence Study of Aripiprazole for Injection in Patients With Schizophrenia.

A Randomized, Open-label, Two-period, Crossover, Steady-state Bioequivalence Study of Aripiprazole for Injection Following Multiple Dosing in Patients With Schizophrenia

The primary objective of this study is to evaluate the bioequivalence of aripiprazole for injection (Test product, 400 mg) compared with Abilify Maintena® (Reference product, 400 mg) at steady state in patients with schizophrenia.his is a multi-center, randomized, open-label, two-period, crossover study. Approximately 116 clinically stable patients will be enrolled and randomly assigned to one of two treatment sequences: Sequence A (Test-Reference) or Sequence B (Reference-Test). In each 141-day study period, participants will receive five injections of either the test or reference product at 28-day intervals to achieve steady-state plasma concentrations. Bioequivalence, safety and tolerability of the study drug will be assessed in this study.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Aripiprazole for Injection; Drug: Aripiprazole for Injection

Detailed Description

Purpose: The primary objective of this study is to evaluate the steady-state bioequivalence between Aripiprazole for Injection (400 mg) manufactured by CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd. (Test product) and Abilify Maintena® (400 mg) manufactured by Otsuka Pharmaceutical (Reference product) in Chinese patients with stable schizophrenia.

Methods: This is a multicenter, randomized, open-label, two-period, crossover, multiple-dose,steady-state bioequivalence study. Approximately 116 eligible patients with stable schizophrenia will be randomly assigned to one of two treatment sequences (Test-Reference or Reference-Test). In each period, subjects will receive five intramuscular injections of either the Test or Reference product (400 mg) at 28-day intervals to ensure that steady-state blood concentrations are achieved by the fourth dose.

Primary Endpoints: Pharmacokinetic (PK) samples will be collected to determine the steady-state maximum plasma concentration (Cmax,ss) and the area under the plasma concentration-time curve over the dosing interval at steady state (AUCτ,ss).

Safety: The safety and tolerability of both formulations will also be monitored and compared throughout the trial.

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Aged 18 to 65 years (inclusive), male or female.
• 2. Patients diagnosed with schizophrenia according to ICD-10 criteria, with a Positive and Negative Syndrome Scale (PANSS) total score ≤ 70, judged as clinically stable for at least 28 days prior to screening (no medication changes or hospitalization due to condition changes).
• 3. Receiving treatment with ≤ 2 other oral antipsychotic medications, which must have been at a stable dose for ≥ 14 days before the first study injection (excluding prohibited medications).
• 4. Body weight ≥ 45 kg for females and ≥ 50 kg for males; Body Mass Index (BMI) between 18.5 and 35.0 kg/m² (inclusive).
• 5. Subject or partner has no pregnancy plan and agrees to use effective non-drug contraception during the study and for six months after the last dose.
• 6. Subjects and their legal guardians voluntarily sign the Informed Consent Form (ICF) and are able to comply with all study requirements.

Exclusion Criteria:

• 1.Diagnosis of any psychiatric disorder other than schizophrenia according to ICD-10 criteria.
• 2.History or presence of clinically significant cardiovascular, hepatic, renal, gastrointestinal, psychiatric, or neurological diseases that, in the investigator's judgment, would affect participation in the study.
• 3.Patients with Parkinson's disease, Lewy body dementia, or dementia-related psychosis.
• 4.History or presence of Neuroleptic Malignant Syndrome (NMS).
• 5.History or presence of epilepsy or convulsive disorders (except childhood febrile seizures), or a history of stroke or transient ischemic attack (TIA) within one year before signing the Informed Consent Form (ICF).
• 6.Concurrent tardive dyskinesia (or history) or severe akathisia.
• 7.Esophageal motility dysfunction or dysphagia with a potential risk of aspiration pneumonia.
• 8.Cardiovascular Risks: Congenital long QT syndrome; presence of uncontrolled or significant cardiovascular disease, including NYHA Class II or higher heart failure, unstable angina, myocardial infarction, or significant arrhythmia/frequent ventricular premature beats within 6 months before the first dose; QTcF > 450 ms in males or > 470 ms in females; presence of risk factors for Torsades de Pointes or sudden death (such as bradycardia, clinically significant hypokalemia, or current use of QTc-prolonging medications; excluding bradycardia judged by the investigator to be risk-controllable and stable after treatment, corrected hypokalemia, or instances where QTc-prolonging medications are discontinued or evaluated as acceptable for stable use) or other clinically significant ECG abnormalities judged by the investigator as potentially affecting subject safety or interfering with study participation.
• 9.Blood Pressure Abnormalities: Poorly controlled hypertension (SBP > 160 mmHg and/or DBP > 100 mmHg after stable antihypertensive treatment); symptomatic hypotension; or orthostatic hypotension (SBP drop ≥ 20 mmHg or DBP drop ≥ 10 mmHg within 3 minutes of standing during screening or baseline).
• 10.Glycosylated hemoglobin (HbA1c) level ≥ 7% at screening or baseline.
• 11.Laboratory Abnormalities: 1) TBiL > 1.5 × ULN, or AST/ALT > 2 × ULN; 2) CLcr < 90 mL/min; 3) WBC < 3 × 10⁹/L, Neutrophils < 1.5 × 10⁹/L, Platelets < 75 × 10⁹/L, RBC < 3.0 × 10¹²/L, or Hemoglobin < 100 g/L.
• 12.Positive results for HBsAg, HCV-Ab, HIV-Ab, or Syphilis-Ab that, in the investigator's judgment, affect study participation.
• 13.Severe Suicide Risk: 1) Positive response to item 4 or 5 of "suicidal ideation" on C-SSRS within the past 6 months; 2) History of suicidal behavior within the past 6 months; or 3) Judged by the investigator to have a severe suicide risk.
• 14.Received electroconvulsive therapy (ECT) or invasive psychiatric treatment within 28 days before signing the ICF.
• 15.History of Blood Loss: Blood loss ≥ 400 mL within 3 months or ≥ 200 mL within 1 month before signing the ICF.
• 16.Major surgery within 3 months before signing the ICF, or planned surgery during the study or within one month after study completion.
• 17.Other Clinical Studies: Participation in any other drug clinical study within one month before the first dose (except for aripiprazole BE studies).
• 18.Long-acting Injectable (LAI) History: Prior treatment with non-aripiprazole LAIs where the interval since the last dose is shorter than the labeled dosing interval of that LAI; or a requirement for other LAIs during the study.
• 19.Medication Contraindications: Use of Chlorpromazine or Thioridazine within 28 days before the first dose; or use of strong/moderate CYP3A4 or CYP2D6 inhibitors or inducers within 14 days or five half-lives (whichever is longer).
• 20.Consumption of foods or beverages rich in xanthines, grapefruit, or caffeine within 48 hours before the first dose, or other special diets that could affect drug pharmacokinetics.
• 21.History of drug abuse, drug usage, or positive drug screening within one year before signing the ICF.
• 22.Chronic Alcohol Consumption: Males > 14 units/week, females > 7 units/week (1 unit ≈ 10g pure alcohol).
• 23.History of needle phobia or blood phobia judged by the investigator to be clinically significant.
• 24.Known or suspected hypersensitivity to the study drug or any of its components.
• 25.Female Status: Women who are pregnant, breastfeeding, or planning to become pregnant (excludes those postmenopausal for ≥ 1 year or surgically sterilized).
• 26.Other conditions that the investigator deems unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A (Test - Reference); Participants receive the Test product (400 mg) in Period 1 and the Reference product (400 mg) in Period 2.	Drug: Aripiprazole for Injection; Subjects will receive a dose of 400 mg (approximately 2 mL) of the test product. The medication is administered via deep intramuscular injection into the gluteal muscle once every 28 days (±1 day). In each study period, subjects will receive a total of 5 injections to ensure steady-state concentrations are achieved.; Other Names: SYH9096; Drug: Aripiprazole for Injection; Subjects will receive a dose of 400 mg (400 mg/2 mL) of the reference product. The medication is administered via deep intramuscular injection into the gluteal muscle once every 28 days (±1 day). In each study period, subjects will receive a total of 5 injections to maintain consistent exposure levels for bioequivalence comparison.; Other Names: Abilify Maintena®
Active Comparator: Sequence B (Reference - Test); Participants receive the Reference product (400 mg) in Period 1 and the Test product (400 mg) in Period 2.	Drug: Aripiprazole for Injection; Subjects will receive a dose of 400 mg (approximately 2 mL) of the test product. The medication is administered via deep intramuscular injection into the gluteal muscle once every 28 days (±1 day). In each study period, subjects will receive a total of 5 injections to ensure steady-state concentrations are achieved.; Other Names: SYH9096; Drug: Aripiprazole for Injection; Subjects will receive a dose of 400 mg (400 mg/2 mL) of the reference product. The medication is administered via deep intramuscular injection into the gluteal muscle once every 28 days (±1 day). In each study period, subjects will receive a total of 5 injections to maintain consistent exposure levels for bioequivalence comparison.; Other Names: Abilify Maintena®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady-state Maximum Plasma Concentration (Cmax,ss) of Aripiprazole	The observed maximum concentration of aripiprazole in plasma at steady state following the 5th intramuscular injection (400 mg) in each study period	Period 1: Day 113 to Day 141 ; Period 2: Day 253 to Day 281
Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady State (AUCτ,ss) of Aripiprazole.	The area under the plasma concentration-time curve for aripiprazole calculated over a dosing interval (28 days) at steady state using the linear up-log down rule.	Period 1: Day 113 to Day 141 ; Period 2: Day 253 to Day 281

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Plasma Concentration (Tmax,ss) of Aripiprazole at Steady State.	The time to reach the maximum observed plasma concentration of aripiprazole after multiple dosing at steady state.	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281
Trough Plasma Concentration (Ctau,ss) of Aripiprazole at Steady State.	The plasma concentration measured at the end of a dosing interval at steady state.	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281
Minimum Plasma Concentration (Cmin,ss) of Aripiprazole at Steady State.	The minimum observed plasma concentration during a dosing interval at steady state.	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281
Terminal Elimination Half-life (t1/2,ss) of Aripiprazole at Steady State.	The time required for the plasma concentration of aripiprazole to decrease by half during the terminal phase at steady state.	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281.
Fluctuation Factor (DF) of Aripiprazole at Steady State.	(Cmax,ss-Cmin,ss)/ Cav,ss	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281.
Steady-state Average Concentration (Cav,ss) of Aripiprazole.	Average concentration at steady state.	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281.
Terminal Elimination Rate Constant (λz,ss) of Aripiprazole at Steady State.	The rate at which aripiprazole is removed from the body.	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281.
Swing of Aripiprazole at Steady State.	(Cmax,ss-Cmin,ss)/ Cmin,ss.	Period 1: Day 113 to Day 141; Period 2: Day 253 to Day 281.
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).	Assessment of safety and tolerability by monitoring the frequency and severity of AEs, SAEs, and changes in laboratory tests, 12-lead ECG, physical examinations, and vital signs.	Day1 to Day281.
CGI Score	The CGI-S is a 7-point scale that measures the clinician's assessment of the severity of the patient's mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).	Day1 to Day281.
C-SSRS	The Columbia-Suicide Severity Rating Scale (C-SSRS) assesses suicidal ideation and behavior.	Day1 to Day281
BARS Score	The BARS is used to assess the severity of drug-induced akathisia. The Global Clinical Assessment score ranges from 0 (absent) to 5 (severe).	Day1 to Day281
AIMS Score	The AIMS is used to assess the presence and severity of tardive dyskinesia. The total score is the sum of items 1 through 7, with each item rated from 0 (none) to 4 (severe).	Day1 to Day281
SAS Score	The SAS is used to assess extrapyramidal symptoms. It consists of 10 items, each rated on a 5-point scale (0 to 4).	Day1 to Day281

Collaborators and Investigators

• Sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 5, 2026
• Primary Completion (Estimated): September 5, 2027
• Study Completion (Estimated): November 5, 2027

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Administration Routes; Drug Therapy; Quinolones; Quinolines; Piperazines; Aripiprazole; Injections
• Other Study ID Numbers: SYH9096-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No