Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients

NCT06608641 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 72189812
• Study Type: interventional
• Target: 490
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Bipolar 1 Disorder

Outcome Measures

Primary Outcomes (1)

• Efficacy - mean change from baseline to Day 21 in the total YMRS score

  Primary efficacy endpoint will be the mean change from baseline to Day 21 in the total YMRS score. The point estimate and 95% confidence interval for the mean change from Day 0 (baseline) to Day 21 in total YMRS score for the difference between test and placebo control treatment will be computed and reported for mITT set. Superiority of test over placebo will be claimed if 95% confidence interval for mean change from Day 0 (baseline) to Day 21 in total YMRS score for the difference between test and placebo control treatment will exclude zero for mITT set.

  27 days

Secondary Outcomes (1)

• Secondary efficacy endpoints

  21 days

Study Arms (2)

Endoxifen Arm

EXPERIMENTAL

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

Drug: Endoxifen enteric-coated tablet (8 mg)

Placebo Arm

PLACEBO COMPARATOR

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

Drug: Placebo Tablets

Interventions

Endoxifen enteric-coated tablet (8 mg) DRUG

Patients will continue treatment with their initial randomized medication for 3 weeks

Endoxifen Arm

Placebo Tablets DRUG

Patients will be treated with Endoxifen Placebo Tablets for 21 days

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male ≥18 to ≤65 years of age and postmenopausal female patients (12 months with no menses without an alternative medical cause) willing to give written informed consent along with at least one first degree relative (the legally acceptable representative \[LAR\]) to participate in the study before initiating any study related procedures.
• Six months of spontaneous amenorrhea with serum FSH levels \>40 mIU/mL; OR have had surgical bilateral oophorectomy (with or without hysterectomy) at least six months ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she is considered not of child-bearing potential.
• Patients must have a diagnosis of bipolar I disorder and currently display an acute manic episode with or without mixed features according to DSM-5 criteria as judged by the Investigator.
• Young Mania Rating Scale (YMRS) total score of \> 25 and ≥4 on two of four core items (irritability, speech, content, disruptive/aggressive behavior) at screening and at randomization (baseline). The optimal YMRS23 severity threshold of 25 was chosen as this corresponds to a Positive Predictive Value (PPV) of 83%, signifying that 83% of patients with a baseline score ≥ 25 are at least "Markedly ill".
• Score of \>4 in Severity of illness criteria of Clinical Global Impressions- bipolar disorder (CGI-BP) Scale for overall illness at screening and at randomization (baseline).
• Ready for voluntary hospitalization (along with the accompanying LAR if required and as advised by the Investigator) for the current manic episode for a minimum of 2 days prior to randomization through 21 days of in-patient treatment period.
• Last intake of the medication(s) for BPD should be 2-7 days prior to randomization depending upon the individual drug's plasma half-life.
• Patient and / or LAR understand and agree to comply with all the study requirements.
• Male patients of child begetting potential must be practicing adequate contraception, and any female partners must agree to the use of, highly effective contraception. Documentation should be provided for surgical sterilization for male patients not of child begetting potential.
• \. Patient has not taken and agrees not to take any medication or therapy prohibited by the protocol (refer to listing in Section 14.7) for the entire study period.
• \. Patients not having any significant diseases or clinically significant abnormal findings except BPD during screening-including medical history, physical examination, laboratory evaluations, 12-lead ECG and X-ray chest (postero- anterior view) recording, etc. which is likely to adversely affect patient\'s safety and may impact the clinical outcome of the study by participating in the study or study objectives in Investigator\'s opinion.
• \. Subjects judged clinically not to be at serious suicide risk, (all responses to the Baseline C-SSRS as "No"), or homicidal risk per clinical questioning.

You may not qualify if:

• Newly diagnosed patients not having any suitable treatment exposure in the past for their bipolar mood disorder.
• ≥ 20% improvement in YMRS total scores between screening and randomization visits.
• Patients who meet DSM-5criteria for any psychiatric disorder other than Bipolar I Disorder with Acute manic episodes with or without mixed features
• Patients with seizure disorder
• Obsessive compulsive disorder or any other co-morbid Axis I anxiety disorder
• Patients with borderline or anti-social personality disorder of sufficient current severity to interfere with conduct of the study
• Patients with classical premenopausal symptoms were found at risk of developing intolerable hot flushes, irregular vaginal bleeding.
• Use of the following medications:
• Antihypertensive agents if stable dose has not been administered for at least 1 month before randomization
• Antidepressants in the week (or a period of 5 half-lives of the drug) prior to randomization
• Continuous daily or standing orders use of benzodiazepines during the month preceding screening (approximately 5 weeks prior to screening)
• Potent cytochrome P450 (CYP) inducers and CYP2D6/CYP3A4 inhibitors 14 days prior to randomization
• Depot antipsychotic medications within 1 dosing interval prior to randomization
• Use of systemic estrogens 6 weeks prior to randomization
• Patients currently on carbapenem agents

Sponsors & Collaborators

• Jina Pharmaceuticals Inc.: lead
• Novum Pharmaceutical Research Services: collaborator

Study Sites (12)

Synexus

Cerritos, California, 90703, United States

Location

NRC Research Institute

Los Angeles, California, 90015, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

Medical Research of Westchester, Inc.

Miami, Florida, 33165, United States

Location

Sunshine Medical Research Studies Inc.

Miami, Florida, 33186, United States

Location

Innovative Clinical Research, Inc.

Miami Lakes, Florida, 33016, United States

Location

South Florida Research Phase I-IV, Inc.

Miami Springs, Florida, 33166, United States

Location

Santos Research Center, CORP

Tampa, Florida, 33615, United States

Location

Accelerated Clinical Trials, LLC

East Point, Georgia, 30344, United States

Location

Accelerated Clinical Trials, LLC

Norcross, Georgia, 30092, United States

Location

Accelerated Clinical Trials, LLC

Peachtree Corners, Georgia, 30071, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All subjects, investigators and research staff will be blinded to the treatment allocation. Only personnel who are not involved in the interpretation and analysis of the study data will be allowed access to the blinded information
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2024
• First Posted: September 23, 2024
• Study Start: March 19, 2024
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 17, 2025

Record last verified: 2024-09

Locations

US (12)