NBI-1070770 for Depression

Recruiting at 12 trial locations

Overseen By Neurocrine Medical Information Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Neurocrine Biosciences

Must be taking: Antidepressants

Disqualifiers: Pregnancy, Unstable conditions, Neurological, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

72 Participants Needed

Trial Summary

What is the purpose of this trial?

To evaluate the efficacy, safety, and tolerability of NBI-1070770 compared to placebo on improving symptoms of depression in participants with major depressive disorder (MDD).

Will I have to stop taking my current medications?

No, you will not have to stop taking your current antidepressant medications. Participants must continue with their current antidepressant medication(s) during the trial.

What makes the drug NBI-1070770 unique for treating depression?

NBI-1070770 may be unique because it potentially involves GABA modulation, which is different from traditional antidepressants that often target monoamine systems. This approach could offer new treatment options for depression, especially for those who do not respond to standard therapies. ^{1 2 3 4 5}

Research Team

Clinical Development Lead

Principal Investigator

Neurocrine Biosciences

Eligibility Criteria

This trial is for adults with recurrent or persistent Major Depressive Disorder (MDD) who've been on their current antidepressants for at least 8 weeks. They must be willing to continue these meds and follow all study rules.

Inclusion Criteria

I've been on my current antidepressants for 8 weeks or more and can keep taking them.

Participants must be willing and able to comply with all study procedures and restrictions

My condition is recurrent or persistent major depression.

Exclusion Criteria

Participant has an alcohol or substance use disorder

Participant is pregnant or breastfeeding or plan to become pregnant during the study

I have a chronic disease or medical condition that is not stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NBI-1070770 or placebo to assess efficacy, safety, and tolerability in improving symptoms of depression

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NBI-1070770

Trial Overview The trial tests NBI-1070770 against a placebo to see if it's better at improving depression symptoms in MDD patients. It measures how safe and tolerable the drug is compared to not receiving the active medication.

Participant Groups

Group I: NBI-1070770: Medium Dose Experimental Treatment 1 Intervention

Participants will receive medium-dose NBI-1070770.

Group II: NBI-1070770: Low Dose Experimental Treatment 1 Intervention

Participants will receive low-dose NBI-1070770.

Group III: NBI-1070770: High Dose Experimental Treatment 1 Intervention

Participants will receive high-dose NBI-1070770.

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo.

Who Is Running the Clinical Trial?

Neurocrine Biosciences

Lead Sponsor

Trials

78

Recruited

6,600+

Kyle W. Gano

Neurocrine Biosciences

Chief Executive Officer since 2024

PhD in Pharmacology

Dr. Sanjay Keswani

Neurocrine Biosciences

Chief Medical Officer

MD

Findings from Research

Research indicates that abnormalities in GABA neurotransmission may play a significant role in the neurobiology of depression, with depressed individuals showing lower levels of GABA in plasma, cerebrospinal fluid, and the brain compared to non-depressed individuals.

Preclinical studies suggest that GABA-modulating agents can exhibit antidepressant effects, leading to increased interest in developing new antidepressant drugs that target GABAergic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. Sanacora, G., Saricicek, A.[2019]

In a study of 43 individuals with major unipolar depression, eight novel variants of the GAD67 gene were identified, but common genetic variations did not show a significant link to depression risk in a larger group of 103 depressed individuals compared to 125 controls.

The research indicates that while GAD67 is crucial for GABA synthesis in the brain, common genetic variations within this gene are unlikely to be a major factor in the predisposition to unipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutation screen of the glutamate decarboxylase-67 gene and haplotype association to unipolar depression. Lappalainen, J., Sanacora, G., Kranzler, HR., et al.[2020]

Ketamine, an NMDA antagonist, has shown rapid improvement in depressive symptoms for patients who do not respond to traditional antidepressants, with effects lasting several days after a low-dose infusion.

A pilot study indicated that a higher-dose, 96-hour infusion of ketamine, combined with clonidine to reduce side effects, resulted in about 40% of subjects maintaining a good response for 8 weeks, highlighting the need for further research to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NMDA Antagonists for Treatment-Resistant Depression. Farber, NB.[2019]

In a 12-week trial with 220 participants, NSI-189 at a 40 mg daily dose showed a significant reduction in depression symptoms on the Symptoms of Depression Questionnaire (SDQ) and Cognitive and Physical Functioning Scale (CPFQ) compared to placebo, suggesting potential efficacy in treating major depressive disorder.

Both doses of NSI-189 were well tolerated, indicating a favorable safety profile, and the findings support further investigation into its antidepressant and cognitive-enhancing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder. Papakostas, GI., Johe, K., Hand, H., et al.[2021]

Major depressive disorder (MDD) is influenced by a complex interplay of various molecular pathways, including neurotransmitter systems, stress responses, neurogenesis, and inflammation, highlighting the multifaceted nature of the disease.

Understanding these interconnected pathways can enhance our comprehension of MDD's neurobiology and potentially lead to improved treatment strategies by focusing on synaptic activity as a key factor in mood and emotion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular pathways of major depressive disorder converge on the synapse. Fries, GR., Saldana, VA., Finnstein, J., et al.[2023]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. [2019]

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

Mutation screen of the glutamate decarboxylase-67 gene and haplotype association to unipolar depression. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

NMDA Antagonists for Treatment-Resistant Depression. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Molecular pathways of major depressive disorder converge on the synapse. [2023]