TV-44749 vs Oral Olanzapine for Schizophrenia

Recruiting at 9 trial locations

Overseen By Teva U.S. Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Must be taking: Olanzapine

Disqualifiers: Diabetes, Hepatic disorder, Arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21 weeks

116 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to be stable on oral olanzapine and not on other antipsychotic treatments at the time of screening. It does not specify about other medications, so it's best to discuss your current medications with the trial investigator.

What data supports the effectiveness of the drug TV-44749, TEV-'749, Olanzapine extended-release injectable suspension for treating schizophrenia?

Research shows that olanzapine, a component of the treatment, is effective in managing schizophrenia symptoms. Studies have demonstrated that long-acting injectable forms of olanzapine can improve adherence to treatment and reduce the risk of relapse in patients with schizophrenia. ^{1 2 3 4 5}

Is the treatment TV-44749 (Olanzapine extended-release injectable suspension) safe for humans?

Olanzapine extended-release injectable suspension has a similar safety profile to the oral form, but there is a small risk (0.07% of injections) of a condition called postinjection delirium sedation syndrome, which is like an overdose and requires monitoring for a few hours after injection. ^{4 5 6 7 8}

How is TV-44749 different from other schizophrenia drugs?

TV-44749 is an extended-release injectable form of olanzapine, which may improve treatment adherence by reducing the frequency of doses compared to oral forms. This long-acting formulation can help ensure consistent medication levels in the body, potentially reducing the risk of relapse in patients with schizophrenia. ^{2 5 7 9 10}

Research Team

Teva Medical Expert, MD

Principal Investigator

Teva Branded Pharmaceutical Products R&D, Inc.

Eligibility Criteria

This trial is for adults with stable schizophrenia, currently on a steady dose of oral olanzapine. Men must be sterile or use birth control, and women should be non-pregnant, postmenopausal, or using contraception. Participants must maintain their smoking status throughout the study.

Inclusion Criteria

I am not pregnant, have had surgery to prevent pregnancy, am past menopause, or use effective birth control.

I am stable on 20 mg of oral olanzapine daily.

Agree to maintain current smoking or nonsmoking status throughout the trial

Exclusion Criteria

I or my family have a history of heart conditions.

I have a mental health condition that is not schizophrenia.

I have diabetes or complications from it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of TV-44749 administered subcutaneously and oral olanzapine to assess comparative bioavailability

21 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TV-44749

Trial Overview The trial is testing TV-44749 given by injection compared to oral olanzapine to see how the body absorbs it in people with schizophrenia. It will also assess safety and measure other drug levels over approximately 21 weeks.

Participant Groups

Group I: TV-44749 Experimental Treatment 1 Intervention

Group II: Oral olanzapine Active Control 1 Intervention

Who Is Running the Clinical Trial?

Teva Branded Pharmaceutical Products R&D, Inc.

Lead Sponsor

Trials

258

Recruited

3,487,000+

Dr. Eric Hughes

Teva Branded Pharmaceutical Products R&D, Inc.

Chief Medical Officer since 2022

MD and PhD from Yale School of Medicine

Richard Francis

Teva Branded Pharmaceutical Products R&D, Inc.

Chief Executive Officer since 2022

Bachelor's degree in Biochemistry from the University of Manchester

Findings from Research

In a 14-week open-label study involving 25 patients with schizophrenia, switching from long-acting injectable antipsychotics to oral olanzapine resulted in significant improvements in overall clinical status and negative symptoms, as measured by the Clinical Global Impression-Improvement Scale and the Positive and Negative Syndrome Scale.

The study also noted a reduction in parkinsonism and dyskinesia among patients who switched to olanzapine, suggesting that this transition may be beneficial in managing side effects associated with injectable antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching outpatients with schizophrenia and related disorders on long-acting injectable antipsychotics to olanzapine: an open-label naturalistic pilot study. Labelle, A., Bourget, D., Boulay, LJ., et al.[2019]

In a 3-month study involving 26 patients with chronic schizophrenia, those switched from depot antipsychotics to oral olanzapine showed significant clinical improvement in symptoms, as measured by various scales, compared to those who continued with depot medications.

Patients transitioning to oral olanzapine reported a preference for this treatment over their previous depot medications, indicating not only efficacy but also better patient satisfaction without significant differences in side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia. Godleski, LS., Goldsmith, LJ., Vieweg, WV., et al.[2019]

In a study of 404 patients with acute schizophrenia, olanzapine long-acting injection (LAI) demonstrated a significant reduction in psychiatric symptoms, with a mean decrease in Brief Psychiatric Rating Scale (BPRS) scores of 14 to 15 points over 6 weeks, comparable to oral olanzapine and haloperidol.

Olanzapine LAI showed a rapid onset of action, with significant symptom improvement observed as early as 3 days, and had a similar efficacy and tolerability profile to oral olanzapine, with fewer extrapyramidal symptoms and no cases of post-injection delirium/sedation syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of olanzapine long-acting injection in patients with acutely exacerbated schizophrenia: an insight from effect size comparison with historical oral data. Detke, HC., Zhao, F., Witte, MM.[2021]

Olanzapine pamoate, a long-acting injectable form of the antipsychotic olanzapine, has shown significant efficacy in treating schizophrenia, with a study of 404 patients demonstrating its effectiveness compared to placebo over 8 weeks.

In a larger study of 1,065 stabilized patients, the depot formulation was effective in delaying the exacerbation of symptoms or hospitalization, with safety profiles similar to oral olanzapine, aside from some local injection reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine: a review of rapid and long-acting parenteral formulations. Owen, RT.[2018]

Olanzapine pamoate (OLAI) has a safety profile similar to oral olanzapine, but it carries a specific risk of post-injection delirium/sedation syndrome (PDSS), which requires monitoring in patients.

OLAI can be a suitable treatment option for schizophrenia patients who have previously responded well to oral olanzapine, provided they have access to emergency care for potential PDSS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine pamoate for the treatment of schizophrenia--a safety evaluation. Samalin, L., Garay, R., Ameg, A., et al.[2018]

Olanzapine pamoate has been shown to be effective for both the acute treatment and maintenance of schizophrenia in two double-blind randomized clinical trials, indicating its potential as a long-acting treatment option.

While the safety profile of olanzapine pamoate is similar to the oral formulation, there is a rare risk (0.07%) of postinjection delirium sedation syndrome, necessitating a 3-hour observation period after injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine pamoate: a stick in time? A review of the efficacy and safety profile of a new depot formulation of a second-generation antipsychotic. Citrome, L.[2018]

In a study involving 8,288 patients, it was found that older patients (50 years or older) experience increased dose-adjusted concentrations of olanzapine when taken orally, indicating that age affects how the body processes this form of the medication.

However, for the long-acting injectable (LAI) formulation of olanzapine, age did not impact systemic exposure, suggesting that LAI can be safely used in older patients without the need for dosage adjustments based on age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age Impacts Olanzapine Exposure Differently During Use of Oral Versus Long-Acting Injectable Formulations: An Observational Study Including 8,288 Patients. Tveito, M., Smith, RL., Molden, E., et al.[2019]

In a 6-year study involving 669 patients with schizophrenia, olanzapine long-acting injection (LAI) demonstrated effectiveness in long-term maintenance treatment, with significant improvements in Clinical Global Impression-Severity scores.

While the safety profile of olanzapine LAI was generally consistent with oral olanzapine, there were notable concerns regarding weight gain (average +2.19 kg, with 40.8% of patients gaining ≥7%) and occurrences of post-injection delirium/sedation syndrome (PDSS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-year open-label study of the efficacy and safety of olanzapine long-acting injection in patients with schizophrenia: a post hoc analysis based on the European label recommendation. Anand, E., Berggren, L., Deix, C., et al.[2020]

The introduction of olanzapine oro-dispersible (Velotab TM) in the UK led to a significant change in prescribing practices among forensic psychiatrists, indicating a preference for this formulation over traditional depot medications.

The study suggests that the ease of administration and reduced opportunity for hiding medication with Velotab TM may improve patient compliance, highlighting the potential benefits of offering more antipsychotics in oro-dispersible forms for patients with compliance issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine oro-dispersible (Velotab TM ) - an alternative to depot? Johnson, D., Rai, S., Milne, S.[2014]

A study involving 24 healthy male volunteers demonstrated that two 10-mg formulations of olanzapine are bioequivalent, meaning they have similar absorption and effectiveness in the body, as shown by comparable pharmacokinetic parameters like Cmax and AUC.

Both formulations were well tolerated with no serious adverse events reported, indicating that they are safe for use in the tested population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of 2 tablet formulations of olanzapine in healthy Chinese volunteers: a randomized, open-label, single-dose study. Chen, Q., Zhang, MQ., Liu, Y., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Switching outpatients with schizophrenia and related disorders on long-acting injectable antipsychotics to olanzapine: an open-label naturalistic pilot study. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of olanzapine long-acting injection in patients with acutely exacerbated schizophrenia: an insight from effect size comparison with historical oral data. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

Olanzapine: a review of rapid and long-acting parenteral formulations. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Olanzapine pamoate for the treatment of schizophrenia--a safety evaluation. [2018]

6. India pubmed.ncbi.nlm.nih.gov

Olanzapine pamoate: a stick in time? A review of the efficacy and safety profile of a new depot formulation of a second-generation antipsychotic. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Age Impacts Olanzapine Exposure Differently During Use of Oral Versus Long-Acting Injectable Formulations: An Observational Study Including 8,288 Patients. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

A 6-year open-label study of the efficacy and safety of olanzapine long-acting injection in patients with schizophrenia: a post hoc analysis based on the European label recommendation. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Olanzapine oro-dispersible (Velotab TM ) - an alternative to depot? [2014]

10. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of 2 tablet formulations of olanzapine in healthy Chinese volunteers: a randomized, open-label, single-dose study. [2018]