Clinical trial NCT06315283: An Open-Label Trial to Assess the Comparative Bioavailability of TV-44749 to Oral Olanzapine in Participants With Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Schizophrenia
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2024-03-18
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area under the curve (AUC) of TV-44749
timeFrame: Days 57 to 84
measure: AUC of oral olanzapine
timeFrame: 24-hour period following administration of the 7th dose
Secondary outcomes:
measure: Number of participants with at least one treatment-emergent adverse event during treatment with TV-44749
timeFrame: Days 1 to 113
measure: Number of participants with at least one treatment-emergent serious adverse event during treatment with TV-44749
timeFrame: Days 1 to 113
measure: Number of participants with at least one injection site adverse event during treatment with TV-44749
timeFrame: Days 1 to 113
measure: Maximum observed plasma drug concentration at steady state (Cmax,ss) of TV-44749
timeFrame: Days 57 to 84
measure: Minimum observed plasma drug concentration at steady state (Cmin,ss) of TV-44749
timeFrame: Days 57 to 84
measure: Cmax,ss of oral olanzapine
timeFrame: 24-hour period following administration of the 7th dose
measure: Cmin,ss of oral olanzapine
timeFrame: 24-hour period following administration of the 7th dose
Other outcomes:
Locations:
city: Los Alamitos
country: United States
facility: Teva Investigational Site 15739
state: California
city: Torrance
country: United States
facility: Teva Investigational Site 15740
state: California
city: Hollywood
country: United States
facility: Teva Investigational Site 15738
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 15741
state: Georgia
city: Decatur
country: United States
facility: Teva Investigational Site 15742
state: Georgia
city: Marlton
country: United States
facility: Teva Investigational Site 15737
state: New Jersey
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60053
city: Zamora
country: Spain
facility: Teva Investigational Site 31326
city: Surrey
country: United Kingdom
facility: Teva Investigational Site 34310
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D LLC
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: