Endoxifen for Bipolar Disorder

Not currently recruiting at 14 trial locations

Overseen By Rishi Kakar

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Jina Pharmaceuticals Inc.

Must not be taking: Antidepressants, Benzodiazepines, Estrogens, others

Disqualifiers: Seizure disorder, Personality disorder, Cardiac conditions, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Endoxifen for individuals with Bipolar I Disorder currently experiencing a manic episode. The goal is to determine if Endoxifen manages mood swings more effectively than a placebo (an inactive substance). Participants will take either Endoxifen or a placebo for a few weeks. Those diagnosed with Bipolar I Disorder and currently experiencing an acute manic episode might be suitable candidates for the trial. As a Phase 3 trial, this is the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking your current medications for bipolar disorder 2-7 days before joining the trial, depending on the specific medication. Additionally, certain other medications are not allowed during the study period.

Do I need to stop my current medications for the trial?

Yes, you will need to stop taking your current medications for bipolar disorder 2-7 days before starting the trial, depending on the specific medication. Additionally, certain other medications are prohibited during the study period.

Is there any evidence suggesting that Endoxifen is likely to be safe for humans?

Research has shown that endoxifen is generally safe for people. Studies reported no serious side effects, though some participants experienced increased blood fat levels over three weeks. Another study found no negative effects, even after eight months of use, suggesting that endoxifen is well-tolerated over time. These findings may reassure those considering joining a clinical trial for bipolar disorder treatment with endoxifen. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar disorder?

Unlike the standard treatments for bipolar disorder, which often focus on mood stabilization through lithium or anticonvulsants, Endoxifen offers a novel approach. Endoxifen is unique because it is derived from tamoxifen, a medication primarily known for treating breast cancer, and it targets estrogen pathways thought to influence mood regulation. This new mechanism of action could potentially provide a faster or more effective way to manage bipolar disorder symptoms compared to traditional methods. Researchers are excited about Endoxifen because it opens up the possibility of treating bipolar disorder through a completely different biological pathway, which could lead to better outcomes for patients who haven't found success with existing therapies.

What evidence suggests that Endoxifen might be an effective treatment for bipolar disorder?

Research has shown that endoxifen, a byproduct of the drug tamoxifen, may help treat bipolar disorder. In studies, patients taking 8 mg of endoxifen improved their manic symptoms, including lower scores on the Young Mania Rating Scale (YMRS), which measures the severity of manic episodes. Some reports also noted that patients needed fewer additional medications like stimulants. In this trial, participants will receive either endoxifen or a placebo. These findings suggest that endoxifen could help manage mood swings and energy levels in people with bipolar disorder. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with Bipolar I Disorder, a condition causing extreme mood swings. Participants must meet specific health criteria to join but details are not provided here.

Inclusion Criteria

Patients and/or LAR must agree to comply with all study requirements

I have been diagnosed with bipolar I disorder and am currently experiencing a manic episode.

Patients must have at least one first-degree relative or legally acceptable representative (LAR) to participate

Exclusion Criteria

Patients with psychiatric disorders other than Bipolar I Disorder with Acute manic episodes

Patients with personality disorders interfering with study conduct

My mood disorder symptoms have improved recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Endoxifen or placebo for 3 weeks to evaluate efficacy and safety in treating acute mania episodes

3 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Endoxifen

Trial Overview The study tests the effectiveness and safety of an 8 mg endoxifen tablet against a placebo in managing symptoms of Bipolar I Disorder. Endoxifen is derived from Tamoxifen, which is already on the market.

How Is the Trial Designed?

Group I: Endoxifen Arm Experimental Treatment 1 Intervention

Endoxifen enteric-coated tablet (8 mg). Patients will continue treatment with their initial randomized medication for 3 weeks

Group II: Placebo Arm Placebo Group 1 Intervention

Placebo tablets. Patients will continue administration with their initial randomized medication for 3 weeks

Endoxifen is already approved in India for the following indications:

Approved in India as Endoxifen for:

• Bipolar I disorder

Who Is Running the Clinical Trial?

Jina Pharmaceuticals Inc.

Lead Sponsor

Trials

7

Recruited

1,700+

Novum Pharmaceutical Research Services

Industry Sponsor

Trials

18

Recruited

6,700+

Published Research Related to This Trial

Z-endoxifen, a potent metabolite of tamoxifen, shows promising antitumor activity in patients with various cancers, including endocrine-refractory metastatic breast cancer, and has substantial oral bioavailability.

Unlike tamoxifen, Z-endoxifen appears to have beneficial effects on bone health while causing little to no endometrial proliferation, making it a potentially safer alternative for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside. Jayaraman, S., Reid, JM., Hawse, JR., et al.[2022]

Tamoxifen has shown significant efficacy in treating acute mania in bipolar disorder, with a strong effect size (SMD -2.14) and higher response rates compared to placebo in five randomized controlled trials lasting three to six weeks.

The acceptability of tamoxifen as a treatment was similar to that of placebo, suggesting it may be a safe option for patients, but further research is needed to explore its long-term effects and potential use alongside other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen for bipolar disorder: Systematic review and meta-analysis. Palacios, J., Yildiz, A., Young, AH., et al.[2020]

A new high-performance liquid chromatography-tandem mass spectrometry assay has been developed and validated to accurately measure endoxifen levels in serum, which is crucial for personalized tamoxifen therapy in breast cancer patients.

In a study of over 500 patients, 32.7% had endoxifen levels below the therapeutic threshold of 5.9 ng/mL, indicating a significant number of patients may be at risk for breast cancer recurrence due to subtherapeutic drug levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast and Adequate Liquid Chromatography-Tandem Mass Spectrometric Determination of Z-endoxifen Serum Levels for Therapeutic Drug Monitoring. de Krou, S., Rosing, H., Nuijen, B., et al.[2017]

In a phase III study involving 116 patients with bipolar I disorder, endoxifen significantly reduced mania symptoms, as measured by the Young Mania Rating Scale, demonstrating strong efficacy (YMRS score decreased from 33.1 to 17.8).

Endoxifen was well-tolerated with no patients requiring rescue medication or withdrawing due to side effects, indicating a favorable safety profile compared to the standard treatment, divalproex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder. Ahmad, A., Sheikh, S., Khan, MA., et al.[2022]

Tamoxifen, while used for treating breast cancer, can lead to significant psychiatric side effects, including worsening depressive symptoms and suicidal thoughts in male patients with a history of mood disorders, as seen in a case study of a 45-year-old man.

Discontinuation of Tamoxifen resulted in a rapid and sustained improvement in the patient's depressive symptoms and suicidal ideation over a one-year follow-up, highlighting the need for careful monitoring of psychiatric effects in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicidality and Illness Course Worsening in a Male Patient with Bipolar Disorder during Tamoxifen Treatment for ER+/HER2+ Breast Cancer. Carmassi, C., Pardini, F., Dell'Oste, V., et al.[2022]

In a double-blind study involving 84 patients with bipolar I disorder, endoxifen demonstrated significant antimanic effects, with improvements in mania observed as early as 4 days and sustained over 21 days.

Response rates for endoxifen were notable, with 44.44% for the 4 mg/day dose and 64.29% for the 8 mg/day dose, indicating its potential as a novel treatment for managing manic episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoxifen, a New Treatment Option for Mania: A Double-Blind, Active-Controlled Trial Demonstrates the Antimanic Efficacy of Endoxifen. Ahmad, A., Sheikh, S., Shah, T., et al.[2019]

(Z)-Endoxifen is a more potent selective estrogen receptor modulator than tamoxifen, showing significant tumor growth inhibition in a preclinical model with female athymic mice at doses of 4-8 mg/kg.

The study confirmed the active configuration of (Z)-endoxifen and developed a validated HPLC method for quality control, ensuring accurate quantitation and impurity profiling, which is crucial for its therapeutic evaluation in ER+ breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the isomeric configuration and impurities of (Z)-endoxifen by 2D NMR, high resolution LC⬜MS, and quantitative HPLC analysis. Elkins, P., Coleman, D., Burgess, J., et al.[2021]

Endoxifen, a potent metabolite of tamoxifen, shows promise as an alternative therapy in breast cancer, but current research primarily focuses on its use in metastatic cases, indicating a need for further studies to establish its therapeutic role.

Pharmacogenetic factors, particularly CYP2D6 genotypes, significantly impact tamoxifen metabolism and clinical outcomes, suggesting that personalized treatment approaches based on genetic testing may be necessary, although evidence for monitoring endoxifen concentrations is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen. Sanchez-Spitman, AB., Swen, JJ., Dezentje, VO., et al.[2019]

In a 28-day study involving 13 women with acute Bipolar Affective Disorder, those treated with tamoxifen showed significant improvement in manic symptoms compared to the placebo group.

The group receiving medroxyprogesterone acetate (MPA) also demonstrated improvement over the placebo, suggesting both hormonal agents may be beneficial adjuncts in treating acute mania.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Kulkarni, J., Garland, KA., Scaffidi, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38683854/

Efficacy and safety of endoxifen in bipolar disorder Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/hup.2899

Efficacy and safety of endoxifen in bipolar disorder: A ... Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04315792

NCT04315792 | Evaluate Efficacy and Safety of Endoxifen ... The present study aims to evaluate the efficacy and safety of 8 mg endoxifen in the study population. As endoxifen represents a totally new class of drugs ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9271003/

Real-World Long-Term Experience on Endoxifen in Bipolar ... Treatment with endoxifen 8 mg once a day showed improvement in manic symptoms with a YMRS score of 4 and a reduction in the use of psychostimulants as well as ...

5. cureus.com cureus.com/articles/302754-endoxifen-in-bipolar-disorder-with-hyperammonemia-and-renal-impairment-a-case-report

Endoxifen in Bipolar Disorder With Hyperammonemia and ... The efficacy and safety of endoxifen are shown in recent multicenter clinical trials for the management of bipolar disorder done by Ahmad et al.

6. cochranelibrary.com cochranelibrary.com/content?templateType=related&urlTitle=/central/doi/10.1002/central/CN-02253931&doi=10.1002/central/CN-02253931&p_p_id=scolariscontentdisplay_WAR_scolariscontentdisplay&_scolariscontentdisplay_WAR_scolariscontentdisplay_action=related-content&p_p_lifecycle=0&p_p_mode=view&type=central&contentLanguage=

Endoxifen: a new, protein kinase C inhibitor to treat acute ... Treating bipolar mania: results of a Multi-Center, Randomized, double-blind and active-controlled, phase III clinical trial of endoxifen for safety and ...