Endoxifen for Bipolar Disorder

Recruiting in Palo Alto (17 mi)

+11 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Jina Pharmaceuticals Inc.

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

Disqualifiers: Seizure disorder, OCD, Personality disorder, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

Bipolar disorder (BPD) is a chronic debilitating illness characterized by drastic swings in mood, energy and functional ability that affects the adult population. Endoxifen is an active metabolite of the marketed drug Tamoxifen and the present study aims to evaluate the efficacy and safety of 8 mg endoxifen in the Bipolar I disorder patient population compared to a placebo arm. Endoxifen will be compared to a placebo to demonstrate that the test product is active and to establish that the study is sufficiently sensitive to detect differences between the investigational products. Thus, Endoxifen will be compared to placebo to demonstrate that the test product is safe and active.

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.

What data supports the effectiveness of the drug Endoxifen for treating bipolar disorder?

Research shows that Endoxifen, a drug related to tamoxifen, has antimanic properties and significantly improved mania symptoms in patients with bipolar I disorder during a 21-day study. Additionally, tamoxifen, a similar drug, has shown effectiveness in reducing manic symptoms in women with bipolar disorder. ^{1 2 3 4 5}

Is endoxifen safe for use in humans?

Endoxifen has been studied in clinical trials for various conditions, including breast cancer and bipolar disorder, and has shown promising safety results. In these studies, it demonstrated good oral bioavailability and did not show significant harmful effects on the endometrium (lining of the uterus) compared to similar drugs. ^{1 2 3 6 7}

How is the drug endoxifen different from other treatments for bipolar disorder?

Endoxifen is unique because it targets the protein kinase C (PKC) signaling system, which plays a role in mood disorders, making it a novel option for treating mania in bipolar disorder. Unlike traditional treatments, endoxifen is an active metabolite of tamoxifen and is administered orally, showing significant improvement in manic symptoms within a few days. ^{1 2 3 8 9}

Research Team

Eligibility Criteria

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

I have been newly diagnosed with bipolar disorder and haven't received treatment yet.

Patients with personality disorders interfering with study conduct

My mood disorder symptoms have improved recently.

Treatment Details

Interventions

• Endoxifen (Selective Estrogen Receptor Modulator)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Synexus Cerritos, CA

NRC Research Institute Los Angeles,, CA

Innovative Clinical Research, Inc. Miami Lakes, FL

NRC Research Institute Orange, CA

More Trial Locations

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+

Findings from Research

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]

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]

(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]

References

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

Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside. [2022]

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

Endoxifen, a New Treatment Option for Mania: A Double-Blind, Active-Controlled Trial Demonstrates the Antimanic Efficacy of Endoxifen. [2019]

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

A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. [2022]

4. United States 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. [2022]

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

Fast and Adequate Liquid Chromatography-Tandem Mass Spectrometric Determination of Z-endoxifen Serum Levels for Therapeutic Drug Monitoring. [2017]

6. Denmark pubmed.ncbi.nlm.nih.gov

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder. [2022]

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

Tamoxifen for bipolar disorder: Systematic review and meta-analysis. [2020]

8. England 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. [2021]

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

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen. [2019]