An Open-Label Trial to Assess the Comparative Bioavailability of TV-44749 to Oral Olanzapine in Participants With Schizophrenia

A 21-Week, Multicenter, Open-Label, Multiple-Dose Trial to Assess the Comparative Bioavailability of Olanzapine Prolonged-Release Suspension for Subcutaneous Administration (TV-44749) to Oral Olanzapine (European Reference) in Participants With Schizophrenia

The primary objective of the study is to evaluate the comparative bioavailability of TV-44749 administered subcutaneous (sc) to oral olanzapine (ZYPREXA®) at steady state in participants with schizophrenia.

A secondary objective of this trial is to evaluate the safety and tolerability of multiple doses of TV-44749 administered sc in participants with schizophrenia.

Another secondary objective of this trial is to compare additional pharmacokinetic parameters of TV-44749 administered sc with oral olanzapine (ZYPREXA®) at steady state in participants with schizophrenia.

The total duration of participation in the trial for each participant is planned to be approximately 21 weeks.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Oral olanzapine; Drug: TV-44749

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 1

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10090
    • Teva Investigational Site 60053
• Spain
  • Zamora, Spain, 49021
    • Teva Investigational Site 31326
• United Kingdom
  • Surrey, United Kingdom, KT22 7AD
    • Teva Investigational Site 34310
• United States
  • California
    • Los Alamitos, California, United States, 90720
      • Teva Investigational Site 15739
    • Torrance, California, United States, 90504
      • Teva Investigational Site 15740
  • Florida
    • Hollywood, Florida, United States, 33024
      • Teva Investigational Site 15738
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Teva Investigational Site 15741
    • Decatur, Georgia, United States, 30030
      • Teva Investigational Site 15742
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Teva Investigational Site 15737

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Agree to maintain current smoking or nonsmoking status at the time informed consent is obtained and throughout the trial until completion of the EOT or ET visit (ie, nonsmoking participants must agree not to start smoking and participants who smoke will be excluded if they plan to discontinue smoking during the trial period).
• Have a current confirmed diagnosis of schizophrenia according to an evaluation by the Investigator, as defined by the DSM-5 (American Psychiatric Association 2013a).
• Are clinically stable on oral olanzapine 20 mg daily (ie, dose has not changed in the last 4 weeks) and not currently on other antipsychotic treatments at the time of screening. Participants on alternative olanzapine regimens (eg, 10 mg twice daily) may be considered for inclusion in the trial based upon the Investigator's clinical judgment.
• Women may be included only if they have a negative serum beta human chorionic gonadotropin (HCG) test result at screening; they are surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (postmenopausal status will be confirmed by a follicle-stimulating hormone screen according to the clinical laboratory standard value) for at least 1 year; or they are practicing a highly effective method of birth control and not planning pregnancy for at least 30 days before the trial, for the duration of the trial, and for 70 days after the last dose administration, if they are sexually active and of childbearing potential.
• Men must be sterile; or if they are potentially of reproductive competence and have sexual relationship with female partners of childbearing potential, they must use, together with their female partners, highly effective birth control methods for the duration of the trial and for 70 days after the last dose administration.

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

Exclusion Criteria:

• History or known risk of narrow-angle glaucoma.
• History or a complication of diabetes (hemoglobin A1c 6.5% or above and/or fasting plasma glucose 126 mg/dL or above).
• Evidence of significant hepatic disorder.
• The participant is a pregnant or lactating woman or plans to become pregnant during the trial or within 70 days after the last dose administration.
• Known hypersensitivity or idiosyncratic reaction to olanzapine (or unable to tolerate oral olanzapine dose) or any of the excipients of TV-44749 in any formulation, their related compounds, or to any metabolites, or any compound listed as being present in TV-44749 or oral olanzapine.
• Presence of excessive pigment, bruises, scars, or tattoos around the potential injection area.
• Personal or family history of arrhythmia, sudden unexplained death at a young age (before 40 years) in a first-degree relative, long QT syndrome, personal history of syncope, or history of uncontrolled high blood pressure. Participants with history of high blood pressure who no longer require treatment or participants who are treated with antihypertensive medications and whose blood pressure is currently well-controlled, may be enrolled.
• Substance use disorder criteria for alcohol, drug, or any other substance dependence (with the exception of nicotine or caffeine) have been met within the past 12 months prior to screening as defined by the DSM-5 (American Psychiatric Association 2013b).
• A current clinically significant DSM-5 diagnosis other than schizophrenia.

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: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral olanzapine	Drug: Oral olanzapine; Administered orally; Other Names: ZYPREXA®
Experimental: TV-44749	Drug: TV-44749; Administered subcutaneously (sc); Other Names: Olanzapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC of oral olanzapine	24-hour period following administration of the 7th dose
Area under the curve (AUC) of TV-44749	Days 57 to 85

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with at least one treatment-emergent adverse event during treatment with TV-44749	Days 1 to 113
Number of participants with at least one treatment-emergent serious adverse event during treatment with TV-44749	Days 1 to 113
Number of participants with at least one injection site adverse event during treatment with TV-44749	Days 1 to 113
Cmax,ss of oral olanzapine	24-hour period following administration of the 7th dose
Maximum observed plasma drug concentration at steady state (Cmax,ss) of TV-44749	Day 57 to Day 85
Plasma concentration at the end of the dosing interval at steady state (Ctrough,ss) of TV-44749	Day 85
Ctrough,ss of oral olanzapine	24-hour period following administration of the 7th dose

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 20, 2024
• Primary Completion (Actual): August 14, 2025
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 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-BA-10196; 2023-505664-11-00 (Registry Identifier: CTIS)

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