Bipolar I DisorderPhase 3NCT04315792
Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients
A Phase 3 study testing Endoxifen in people with Bipolar I Disorder, run by Jina Pharmaceuticals Inc. at 1 site in United States.
Trial summary
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 in the treatment of the bipolar disorder, it is essential to compare the drug against placebo to rule out the psychological influence upon study results. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar I Disorder
- What is being tested?
- Endoxifen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2020to 25 Aug 2021
- 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 and female patients, 18 to 65 (both inclusive) years of age 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.
- Patients must have a diagnosis of bipolar I disorder and currently display an acute manic episodes with or without mixed features according to DSM-5 criteria as judged by the Investigator.
- Young Mania Rating Scale (YMRS) total score of > 20 and ≥4 on two of four core items (irritability, speech, content, disruptive/aggressive behavior) at screening and at randomization (baseline).
- 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 2 days prior to randomization up to 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.
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- 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.
- Females of reproductive potential (which include girls who have entered puberty and all women who have a uterus and ovaries and have not completed menopause), must use anacceptable and effective method of avoiding pregnancy, starting at least four weeks before the first dose of study drug and continuing until at least one month after the last dose of study drug.
- Subjects judged clinically not to be at serious suicide risk.
Who cannot join
- Newly diagnosed patients and 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-5 criteria for any psychiatric disorder other than Bipolar I Disorder with Acute Mania Episode 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 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
- De compensatory 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, gastroenterologic, 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 (with the exception of 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 or homicidal ideation.
- Participation in a clinical trial of another investigational drug within 30 days prior to screening.
Trial locations and contacts
1 site in 1 country.
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
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 in the treatment of the bipolar disorder, it is essential to compare the drug against placebo to rule out the psychological influence upon study results. More so given the risks to patients and their communities from a medication whose efficacy has not been thoroughly evaluated against a placebo control. Thus, Endoxifen will be compared to 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.
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 I Disorder
- Being tested
- Endoxifen, Placebo oral tablet
- Keywords
- Endoxifen, Bipolar I Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndoxifenDrug
Administration of Endoxifen for 3 weeks
Placebo oral tabletDrug
Administration of Placebo for 3 weeks
| 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 |
| Placebo Arm | Placebo comparator | Placebo tablets of endoxifen. Patients will continue administration with their initial randomized medication for 3 weeks Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the efficacy and establish superiority of endoxifen 8 mg against placebo in Bipolar I Disorder patients (Mean change in total YMRS score)
Mean change in total YMRS score at Day 21 against baseline (in-patient setup)
Measured: 3 weeks
Secondary outcomes (1)
Evaluate the safety and tolerability of all the treatments among Bipolar I Disorder patients (treatment related adverse events)
All treatment related adverse events including abnormal laboratory parameters
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start3 Aug 2020
- Primary completion25 Jan 2021
- Study completion25 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar I 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jina Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novum Pharmaceutical Research Services, Lambda Therapeutic Research Ltd.
- Responsible party
- Sponsor
- Investigators
- Theodore R Treese, MD, Principal investigator, Innovative Clinical Research, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04315792
- Sponsor's protocol ID
- 0791-17
- Status last verified
- Sep 2024
- First submitted
- 16 Mar 2020
- Last updated
- 23 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. 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
- ClinicalTrials.gov ID
- NCT04315792
- Acronym / sponsor ID
- 0791-17
- Conditions
- Bipolar I Disorder
- Keywords
- Endoxifen, Bipolar I Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Jina Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- Novum Pharmaceutical Research Services, Lambda Therapeutic Research Ltd.
- Study start
- 3 Aug 2020 (actual)
- Primary completion
- 25 Jan 2021 (actual)
- Study completion
- 25 Aug 2021 (actual)
- First posted
- 20 Mar 2020 (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.
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 in the treatment of the bipolar disorder, it is essential to compare the drug against placebo to rule out the psychological influence upon study results. More so given the risks to patients and their communities from a medication whose efficacy has not been thoroughly evaluated against a placebo control. Thus, Endoxifen will be compared to 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.
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
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endoxifen Arm | Experimental | Drug: EndoxifenEndoxifen enteric-coated tablet (8 mg). Patients will continue treatment with their initial randomized medication for 3 weeks |
| Placebo Arm | Placebo comparator | Drug: Placebo oral tabletPlacebo tablets of endoxifen. 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 (10 listed)
- Male and female patients, 18 to 65 (both inclusive) years of age 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.
- Patients must have a diagnosis of bipolar I disorder and currently display an acute manic episodes with or without mixed features according to DSM-5 criteria as judged by the Investigator.
- Young Mania Rating Scale (YMRS) total score of > 20 and ≥4 on two of four core items (irritability, speech, content, disruptive/aggressive behavior) at screening and at randomization (baseline).
- 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 2 days prior to randomization up to 21 days of in-patient treatment period.
Key exclusion criteria (39 listed)
- Newly diagnosed patients and 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-5 criteria for any psychiatric disorder other than Bipolar I Disorder with Acute Mania Episode 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 |
|---|---|---|
| EndoxifenAdministration of Endoxifen for 3 weeks | Drug | Endoxifen Arm |
| Placebo oral tabletAdministration of Placebo for 3 weeks | Drug | Placebo Arm |
Primary outcome
Evaluate the efficacy and establish superiority of endoxifen 8 mg against placebo in Bipolar I Disorder patients (Mean change in total YMRS score)
Time frame: 3 weeks
Mean change in total YMRS score at Day 21 against baseline (in-patient setup)
1 secondary outcome
Evaluate the safety and tolerability of all the treatments among Bipolar I Disorder patients (treatment related adverse events)
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Individual participant dataSharing planned: No
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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.
Theodore R Treese, MD principal investigator
Innovative Clinical Research, Inc.
1 site 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 in people with Bipolar I Disorder, run by Jina Pharmaceuticals Inc. at 1 site 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 10 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: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluate the efficacy and establish superiority of endoxifen 8 mg against placebo in Bipolar I Disorder patients (Mean change in total YMRS score) (time frame: 3 weeks). 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 23 Sep 2024.