Bipolar 1 DisorderPhase 3NCT06608641
Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients
A Phase 3 study testing Endoxifen enteric-coated tablet (8 mg) in people with Bipolar 1 Disorder, run by Jina Pharmaceuticals Inc. at 12 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar 1 Disorder
- What is being tested?
- Endoxifen enteric-coated tablet (8 mg)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 490 participants
- Where
- 12 sitesUnited States
- Study dates
- 19 Mar 2024to Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 11. 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.
- 12. 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.
- 13. 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.
Who cannot join
- 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
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- 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
- Any of the following laboratory abnormalities
- Serum bilirubin ≥ 1.5 times ULN
- Serum AST/ALT ≥ 2.5 times ULN
- Serum TSH \>10% above the ULN, regardless of treatment for hypothyroidism or hyperthyroidism
- Serum triglyceride level \> 2.5 times ULN
- Patients with the following cardiac conditions are excluded:
- Recent myocardial infarction (\<12 months)
- QTc prolongation (screening electrocardiogram with QTc \> 450 msec for men, QTc \> 470 msec for women)
- History of QTc prolongation or using concomitant medications (as judged by the Investigator) which prolong QTc interval
- Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia
- Decompensatory congestive heart failure
- Complete left bundle branch block
- First-degree heart block with PR interval \> 0.22 seconds
- Presence of a coagulation disorder; active or past history of venous thromboembolism including deep venous thrombosis or pulmonary embolism
- Current prolonged immobilization
- History or current presence of retinal pathology including retinal vein thrombosis
- Increased risk of stroke as per the Investigator's discretion
- History of hypersensitivity or intolerance to tamoxifen, or any other ingredients of the preparation
- Serious, unstable illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease as per history and medical examination.
- Drug screen positive for any drug of abuse at screening, (except for benzodiazepines used in therapeutic dose for management of acute mania), active substance abuse in the past 2 months or history of substance dependence (excluding nicotine and caffeine) within 3 months of screening.
- History of breast or uterine cancer, or abnormal uterine bleeding.
- Current leukopenia or thrombocytopenia as judged by the Investigator in the best health interest of the subject.
- Clinically significant suicidal (subject responds "Yes" to any category for Baseline C-SSRS) or homicidal ideation per clinical questioning.
- Participation in a clinical trial of another investigational drug within 30 days prior to screening.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Synexus
Cerritos, California, 90703
Accelerated Clinical Trials, LLC
East Point, Georgia, 30344
Precise Research Centers
Flowood, Mississippi, 39232
NRC Research Institute
Los Angeles, California, 90015
Medical Research of Westchester, Inc.
Miami, Florida, 33165
Sunshine Medical Research Studies Inc.
Miami, Florida, 33186
Innovative Clinical Research, Inc.
Miami Lakes, Florida, 33016
South Florida Research Phase I-IV, Inc.
Miami Springs, Florida, 33166
Accelerated Clinical Trials, LLC
Norcross, Georgia, 30092
NRC Research Institute
Orange, California, 92868
Accelerated Clinical Trials, LLC
Peachtree Corners, Georgia, 30071
Santos Research Center, CORP
Tampa, Florida, 33615
About this study
Official title: A Double-blind, Oral, Multiple-dose, Parallel, Randomized Study to Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients With Acute Mania Episodes With or Without Mixed Features
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.
Read the detailed description
Protein Kinase C (PKC) plays a major role in the regulation of both pre and postsynaptic neurotransmission. Excessive activation of PKC results in symptoms related to bipolar disorder. PKC exists as a family of closely related subspecies, has a heterogeneous distribution in the brain (with particularly high levels in presynaptic nerve terminals), and plays a crucial role in the regulation of neuronal excitability, neurotransmitter release, regulation of synaptic plasticity and various forms of learning and memory. Research findings show that the PKC pathway can be used as a target for developing treatment strategies for bipolar disorder. Endoxifen exhibited activity in inhibiting the PKC activity.
In patients with acute bipolar mania, rapid reduction of symptoms is a key treatment goal; however, there is also a need for effective maintenance of effect treatment beyond the period of acute stabilization. The current study will evaluate the efficacy and safety of Endoxifen in Bipolar I Disorder patients against a control placebo arm.
- Conditions
- Bipolar 1 Disorder
- Being tested
- Endoxifen enteric-coated tablet (8 mg), Placebo Tablets
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endoxifen enteric-coated tablet (8 mg)Drug
Patients will continue treatment with their initial randomized medication for 3 weeks
Placebo TabletsDrug
Patients will be treated with Endoxifen Placebo Tablets for 21 days
| Study group | Role | What they receive |
|---|---|---|
| Endoxifen Arm | Experimental | Endoxifen enteric-coated tablet (8 mg). Patients will continue treatment with their initial randomized medication for 3 weeks Receives: 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 Receives: Drug: Placebo Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 27 days
Secondary outcomes (1)
Secondary efficacy endpoints
- Percentage of patients with improvement of ≥ 50% in total YMRS from baseline.
- Clinical Global Impression-Bipolar (CGI-BP) score at the end of study.
- Mean change from baseline to the end of treatment in Montgomery-Åsberge Depression Rating Scale (MADRS) total score.
- Improvement in Clinical Global Impression-Severity of Illness scale (CGI-S) score.
- Columbia-Suicide Severity Rating Scale (C-SSRS) score at the end of treatment.
- Percentage of patients needing lorazepam/diazepam for controlling acute agitation/akathisia.
- Percentage of patients requiring rescue medications and withdrawal from the study.
- To evaluate trough concentrations of Endoxifen.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2024
- Study start19 Mar 2024
- Primary completionJun 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar 1 DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 490 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jina Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novum Pharmaceutical Research Services
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06608641
- Sponsor's protocol ID
- 72189812
- Status last verified
- Sep 2024
- First submitted
- 18 Sep 2024
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Oral, Multiple-dose, Parallel, Randomized Study to Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients With Acute Mania Episodes With or Without Mixed Features
- ClinicalTrials.gov ID
- NCT06608641
- Acronym / sponsor ID
- 72189812
- Conditions
- Bipolar 1 Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 490 participants (estimated)
- Lead sponsor
- Jina Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- Novum Pharmaceutical Research Services
- Study start
- 19 Mar 2024 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 23 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Protein Kinase C (PKC) plays a major role in the regulation of both pre and postsynaptic neurotransmission. Excessive activation of PKC results in symptoms related to bipolar disorder. PKC exists as a family of closely related subspecies, has a heterogeneous distribution in the brain (with particularly high levels in presynaptic nerve terminals), and plays a crucial role in the regulation of neuronal excitability, neurotransmitter release, regulation of synaptic plasticity and various forms of learning and memory. Research findings show that the PKC pathway can be used as a target for developing treatment strategies for bipolar disorder. Endoxifen exhibited activity in inhibiting the PKC activity.
In patients with acute bipolar mania, rapid reduction of symptoms is a key treatment goal; however, there is also a need for effective maintenance of effect treatment beyond the period of acute stabilization. The current study will evaluate the efficacy and safety of Endoxifen in Bipolar I Disorder patients against a control placebo arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endoxifen Arm | Experimental | Drug: Endoxifen enteric-coated tablet (8 mg)Endoxifen enteric-coated tablet (8 mg). Patients will continue treatment with their initial randomized medication for 3 weeks |
| Placebo Arm | Placebo comparator | Drug: Placebo TabletsPlacebo tablets. Patients will continue administration with their initial randomized medication for 3 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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).
Key exclusion criteria (39 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endoxifen enteric-coated tablet (8 mg)Patients will continue treatment with their initial randomized medication for 3 weeks | Drug | Endoxifen Arm |
| Placebo TabletsPatients will be treated with Endoxifen Placebo Tablets for 21 days | Drug | Placebo Arm |
Primary outcome
Efficacy - mean change from baseline to Day 21 in the total YMRS score
Time frame: 27 days
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.
1 secondary outcome
Secondary efficacy endpoints
Time frame: 21 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Endoxifen enteric-coated tablet (8 mg) in people with Bipolar 1 Disorder, run by Jina Pharmaceuticals Inc. at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy - mean change from baseline to Day 21 in the total YMRS score (time frame: 27 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2025.