Safety, Tolerability, and Pharmacokinetic Study of TV-44749 in Chinese Patients With Schizophrenia

A Phase 1, Single Dose, Parallel Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TV-44749, Olanzapine for Extended-Release Injectable Suspension for Subcutaneous Use, in Chinese Patients With Schizophrenia

Primary Objective:

To evaluate the safety and tolerability of single doses of TV-44749 for subcutaneous (sc) use in Chinese participants with schizophrenia.

Secondary Objectives:

• To evaluate the pharmacokinetics (PK) of single doses of TV-44749 administered sc.
• To evaluate the pharmacokinetics of oral olanzapine tablets following multiple dose administration.
• To monitor the safety and tolerability of multiple doses of oral olanzapine tablets given in the study.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: TV-44749 318mg; Drug: Oral Olanzapine 10mg/day; Drug: TV-44749 425mg; Drug: Oral Olanzapine 15mg/day; Drug: TV-44749 531mg; Drug: Oral Olanzapine 20mg/day

Detailed Description

The total study duration for participants is planned to be approximately 13 weeks, including 40 days of screening, 1-week oral olanzapine treatment, a 1-week washout period, 4-week TV-44749 treatment, and 2-week follow-up period after the last dosing interval.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100088
    • Teva Investigational Site 88049
  • Beijing, China, 100191
    • Teva Investigational Site 88048
  • Guangzhou, China, 510370
    • Teva Investigational Site 88047
  • Shanghai, China, 200030
    • Teva Investigational Site 88046
  • Wuhan, China, 430022
    • Teva Investigational Site 88050
  • Xi'an, China, 710061
    • Teva Investigational Site 88056

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body weight >50 kg and body mass index (BMI) between 18.5 to 38.0 kg/m2, inclusive, at the time of screening.
• A current confirmed diagnosis of schizophrenia according to an evaluation by the investigator, using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Are clinically stable, on oral olanzapine (i.e., dose has not changed in the last 4 weeks), and not currently on other antipsychotic treatment at the time of screening.
• No hospitalization for worsening of schizophrenic symptoms and no significant exacerbation of schizophrenic symptoms, as judged by the investigator, within the 3 months prior to screening.
• Female participants must have a negative serum pregnancy test at screening, are sterile or postmenopausal, and not planning pregnancy within the study period and for an additional 6 months after last dose administration.
• Male participants must be surgically sterile, or, if capable of producing offspring, has exclusively same-sex partners or is currently using an approved method of birth control.
• Agree to maintain current smoking or nonsmoking status at the time informed consent is obtained and throughout the study until completion of the end of study (EOS)/early termination (ET) visit.
• Have no ongoing or expected significant life events (such as pending loss of housing, marital status change, long travel abroad, surgery, etc.) that could affect study outcomes expected throughout the period of study participation.

NOTE: Additional criteria apply, please contact the investigator for more information.

Exclusion Criteria:

• Presence or have a history of clinically significant diseases of the renal, hepatic, gastrointestinal, cardiovascular, musculoskeletal system or presence or history of clinically significant immunological, endocrine, metabolic, neurological, or psychiatric disorder(s) (other than schizophrenia), or a history of any illness that, in the opinion of the principal investigator, might pose additional risk to the participant by participation in the study or confound the results of the study
• Major trauma or surgery in the 2 months before screening or at any time between screening and the first dose of the investigational medicinal product (IMP), surgery scheduled during the study or follow-up period, or open biopsy within 4 months prior to screening
• History of malignancy or treatment of malignancy in the last 5 years, excluding resected basal cell or squamous cell carcinoma of the skin.

NOTE: Additional criteria apply, please contact the investigator for more information.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Period 1: Participants will receive oral olanzapine daily Period 2: Participants will receive subcutaneous (sc) injection of TV-44749	Drug: TV-44749 318mg; Pharmaceutical form: extended-release injectable suspension Route of administration: subcutaneous injection; Drug: Oral Olanzapine 10mg/day; Pharmaceutical form: tablet Route of administration: oral; Other Names: ZYPREXA
Experimental: Cohort 2; Period 1: Participants will receive oral olanzapine daily Period 2: Participants will receive sc injection of TV-44749	Drug: TV-44749 425mg; Pharmaceutical form: extended-release injectable suspension Route of administration: subcutaneous injection; Drug: Oral Olanzapine 15mg/day; Pharmaceutical form: tablet Route of administration: oral; Other Names: ZYPREXA
Experimental: Cohort 3; Period 1: Participants will receive oral olanzapine daily Period 2: Participants will receive sc injection of TV-44749	Drug: TV-44749 531mg; Pharmaceutical form: extended-release injectable suspension Route of administration: subcutaneous injection; Drug: Oral Olanzapine 20mg/day; Pharmaceutical form: tablet Route of administration: oral; Other Names: ZYPREXA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Period 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all serious AEs (SAEs), regardless of causality is located in the Reported AE section.	Day 1 Up to Day 43
Period 2: Number of Participants With Treatment Emergent SAEs	An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. The SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section.	Day 1 Up to Day 43
Period 2: Number of Participants With Injection Site AEs	Injection site AEs included injection site pruritus, induration, warmth, and abscess. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section. All injection site AEs are reported in this outcome measure and the AE module only reports non-serious AEs at the 5% threshold. In the AE module, a participant could have been included for multiple injection site AEs.	Day 1 Up to Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Period 2: Maximum Observed Plasma Drug Concentration (Cmax) of TV-44749		Day 1 Up to Day 43
Period 2: Time to Maximum Observed Concentration (Tmax) of TV-44749		Day 1 Up to Day 43
Period 2: Apparent Elimination Half-Life (t½) of TV-44749		Day 1 Up to Day 43
Period 2: Area Under the Plasma Drug Concentration-time Curve (AUC) Over the Period Following Administration on Day 1 to the Time of the Last Measurable Concentration (AUC0-t) of TV-44749		Day 1 Up to Day 43
Period 2: AUC of TV-44749 Over the Period Following Administration on Day 1 Extrapolated to Infinity (AUC0-inf)		Day 1 Up to Day 43
Period 1: Maximum Observed Plasma Drug Concentration at Steady State (Cmax,ss[Oral Olanzapine])		Day -8
Period 1: AUC of Oral Olanzapine From Time 0 to the End of the Dosing Interval (24 Hour) at Steady State (AUC0-tau,ss[Oral Olanzapine])		Day -8
Period 1: Calculated AUC of Oral Olanzapine at Steady State Extrapolated Over 28 Days (AUC0-tau,ss[Oral Olanzapine] * 28)	The steady-state AUC of oral olanzapine over a 28-day dosing interval was calculated by extrapolating the 24-hour AUC obtained following administration of the seventh oral dose (Day -8) to a 28-day period (AUC0-tau,ss[oral olanzapine] * 28).	Day -8 up to Day 20
Period 1: Time to Maximum Concentration of Oral Olanzapine at Steady State (Tmax,ss[Oral Olanzapine])		Day -8
Period 1: Number of Participants With TEAEs	An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section.	Day -14 up to Day -8
Period 1: Number of Participants With Treatment Emergent SAEs	An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. The SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-SAEs and all serious AEs, regardless of causality is located in the Reported AE section.	Day -14 up to Day -8

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D LLC
• Investigators: Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2024
• Primary Completion (Actual): June 12, 2025
• Study Completion (Actual): June 12, 2025

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 2, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Olanzapine
• Other Study ID Numbers: TV44749-PK-10188

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be assessed for scientific merit, product approval status, and conflicts of interest. If the request is approved, patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.

Drug and device information, study documents

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