TV-44749 for Schizophrenia

(SOLARIS Trial)

Recruiting at 94 trial locations

Overseen By Teva U.S. Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

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

Must be taking: Antipsychotics

Must not be taking: Clozapine, LAI antipsychotics

Disqualifiers: Bipolar, Dementia, Substance use, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 22

675 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called TV-44749 to see if it helps adults with schizophrenia, especially those with worsening symptoms. The medication likely works by balancing brain chemicals to reduce symptoms. The study will last over a year, with different phases to test both its effectiveness and safety.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using a long-acting injectable antipsychotic, taking clozapine, or receiving daily oral olanzapine at a dose greater than 20 mg/day.

What data supports the effectiveness of the drug TV-44749 for treating schizophrenia?

Olanzapine, a component of TV-44749, has been shown to be effective in treating schizophrenia, with studies demonstrating that its long-acting injectable form can significantly reduce symptoms and delay relapses. This form of olanzapine is particularly useful for patients who have trouble sticking to their medication schedule, as it can be administered every few weeks. ^{1 2 3 4 5}

What safety data exists for TV-44749 (Olanzapine extended-release injectable suspension) in humans?

Olanzapine, including its long-acting injectable form, has been studied for safety in treating schizophrenia. Common side effects include sleepiness, weight gain, and mild liver enzyme changes, but serious side effects like seizures and sexual dysfunction are rare. No new safety concerns have been noted beyond those seen with the oral form. ^{3 6 7 8 9}

What makes the drug TV-44749 unique for treating schizophrenia?

TV-44749 is unique because it is an extended-release injectable form of olanzapine, allowing for less frequent dosing (every 2 to 4 weeks) compared to daily oral tablets, which can improve patient compliance and maintain stable drug levels over time. ^{3 9 10 11 12}

Research Team

Teva Medical Expert, MD

Principal Investigator

Teva Branded Pharmaceutical Products R&D, Inc.

Eligibility Criteria

Adults with recent schizophrenia flare-ups, a BMI of 18-40, and diagnosed over a year ago can join. Women must not plan pregnancy and use contraception. Excluded are those hospitalized for over 14 days recently, at risk of violence or suicide, on certain antipsychotics or treatments like clozapine in the past year, have significant other mental health diagnoses or substance abuse issues.

Inclusion Criteria

My schizophrenia symptoms worsened in the last 8 weeks, needing hospital care.

Body mass index between 18.0 and 40.0 kg/m2, inclusive, at the time of screening

My overall health, including heart and blood tests, is good.

Exclusion Criteria

I am currently on long-acting injectable antipsychotics.

The participant has a non-fasting glucose level of ≥200 mg/dL at screening

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Double-blind, placebo-controlled, efficacy and safety period with weekly visits

8 weeks

8 visits (in-person)

Treatment Period 2

Open-label long-term safety period with monthly in-clinic visits and weekly calls

48 weeks

12 visits (in-person), weekly calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

2 visits (in-person)

Treatment Details

Interventions

• TV-44749

Trial Overview The trial tests TV-44749's effectiveness in adults with schizophrenia across three different doses compared to a placebo. It assesses improvement from baseline to week 56 with weekly then monthly check-ins.

Participant Groups

Group I: TV-44749 - Dose level 3 Experimental Treatment 1 Intervention

High dose regimen

Group II: TV-44749 - Dose level 2 Experimental Treatment 1 Intervention

Medium dose regimen

Group III: TV-44749 - Dose level 1 Experimental Treatment 1 Intervention

Low dose regimen

Group IV: Placebo Placebo Group 1 Intervention

Matching Placebo

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 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]

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]

In a clinical safety review involving 2500 patients treated with olanzapine for acute schizophrenia, the overall discontinuation rate was low, indicating good tolerability of the medication.

While olanzapine was associated with some significant adverse effects such as somnolence, weight gain, and elevated liver enzymes, it showed minimal risk for parkinsonism, akathisia, and no cases of hematotoxicity, making it a relatively safe option compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of olanzapine. Beasley, CM., Tollefson, GD., Tran, PV.[2018]

Paliperidone extended-release tablets (3-12 mg/day) were effective in maintaining symptom improvements in schizophrenia patients over a 52-week open-label extension phase, following initial 6-week placebo-controlled trials involving 1083 participants.

The treatment was generally well tolerated, with common side effects including insomnia, headache, and akathisia, while serious adverse events occurred in 16% of patients, including two suicides, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies. Emsley, R., Berwaerts, J., Eerdekens, M., et al.[2015]

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]

Olanzapine pamoate (OLAI) has been shown to be more effective than placebo in treating symptoms of schizophrenia in two pivotal trials lasting 8 or 24 weeks, and it is comparable to oral olanzapine in preventing psychotic exacerbations for patients stabilized on the oral form.

OLAI is generally well tolerated, with a low incidence of post-injection syndrome (<0.1%), but requires a risk management plan for monitoring after administration, making it a suitable option for patients who struggle with adherence to oral medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine long-acting injection: a review of its use in the treatment of schizophrenia. Frampton, JE.[2021]

References

1. 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]

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

Patient perspectives in the development and use of long-acting antipsychotics in schizophrenia: focus on olanzapine long-acting injection. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

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

4. Hungary pubmed.ncbi.nlm.nih.gov

[Olanzapine pamoate injection -- experience and case reports from Hungarian clinical practice]. [2018]

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

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

6. 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]

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

Safety of olanzapine. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies. [2015]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

D2 receptor occupancy of olanzapine pamoate depot using positron emission tomography: an open-label study in patients with schizophrenia. [2022]

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

Olanzapine long-acting injection: a review of its use in the treatment of schizophrenia. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Formulation and evaluation of olanzapine matrix pellets for controlled release. [2021]