What Is Seltorexant?
Seltorexant is an investigational drug that has been studied in clinical trials for various conditions. It is primarily administered orally as a tablet, with some studies also involving an intravenous infusion. While the specific mechanism of action is not detailed in the provided descriptions, research is exploring its effects in the body. Seltorexant is being investigated for its potential therapeutic benefits in conditions such as Major Depressive Disorder, Alzheimer Disease, and Obstructive Sleep Apnea. Additionally, studies have been conducted in healthy participants and those with specific characteristics like recreational sedative users to assess its safety, how it is processed by the body (pharmacokinetics), and its potential for abuse. A total of 14 clinical trials have been conducted or are currently recruiting for seltorexant, with a combined enrollment of 2,983 participants. The first trial for seltorexant began in 2018, and the most recent trial started in 2024. All clinical research for seltorexant is sponsored by Janssen Research & Development, LLC.
Uses and Conditions Under Study
Seltorexant is being investigated across several distinct conditions in clinical trials.
A significant area of research focuses on Major Depressive Disorder, a common mood disorder. Seltorexant has been studied in 6 trials for this condition, indicating a substantial effort to understand its potential effects on depressive symptoms.
Another condition under investigation is Alzheimer Disease, a progressive disorder that impacts memory and other cognitive abilities. Seltorexant is being explored in 1 trial for its potential role in managing aspects of this disease.
Obstructive Sleep Apnea, a condition characterized by repeated interruptions in breathing during sleep, is also being studied. 1 trial is evaluating seltorexant for its potential to address this sleep disorder.
In addition to these therapeutic areas, several trials have focused on understanding the drug's fundamental properties and safety. These studies include:
- Trials involving healthy participants, totaling 5 studies, to assess the drug's pharmacokinetics (how the body processes it) and overall safety.
- One trial specifically investigated the abuse potential of seltorexant.
- Another trial included healthy non-dependent, recreational sedative users to further evaluate safety and effects in a specific population.
Dosing
Seltorexant has been investigated in clinical trials using different dosage forms and administration schedules. The most common method of administration is orally as a tablet. In specific research studies, seltorexant was also administered as an intravenous infusion, particularly when using 14C-seltorexant for metabolic tracing.
Dosage strengths have varied across the studies. A specific oral tablet strength of 20 mg has been investigated. Other trials have explored both "low dose" and "high dose" formulations of seltorexant to determine optimal therapeutic effects and safety.
Regarding administration frequency, some studies involved a single oral dose of seltorexant. Other research protocols specified that the seltorexant tablet be administered orally once daily. These varied approaches allow researchers to comprehensively evaluate the drug's effects, safety, and appropriate dosing regimens for the conditions under study. Placebo-matched formulations were also used in trials to compare seltorexant's effects against an inactive substance.
Side Effects
In clinical trials, the most commonly reported side effect for Seltorexant was headache. Across two trials involving 291 patients taking Seltorexant, 4.8% experienced headaches, compared to 4.2% of patients receiving a placebo.
Other side effects were observed in a smaller study involving 81 patients taking Seltorexant. In this trial, 1.2% of patients on Seltorexant experienced the following, while no patients on placebo reported these events:
- Bronchitis
- Confusional arousal
- Abnormal dreams
- Malignant biliary obstruction
- Supraventricular extrasystoles
- Dysphonia
- Haemorrhoids
- Neck pain
- Orchitis
- Pruritus
Nasopharyngitis (inflammation of the nose and throat) was reported by 1.2% of patients taking Seltorexant and 1.2% of patients on placebo in the same smaller trial.
Clinical Trial Results
Major Depressive Disorder with Insomnia Symptoms
A study (NCT04532749) evaluated Seltorexant as an add-on treatment for adults with major depressive disorder and insomnia who had not responded well to standard antidepressant therapy. After 43 days, Seltorexant showed improvements in several measures:
- Depression Symptoms (MADRS): Patients taking Seltorexant experienced an average reduction of 14.0 units on the Montgomery-Asberg Depression Rating Scale (MADRS), indicating an improvement in depressive symptoms. Patients on placebo saw an average reduction of 13.1 units.
- Sleep Disturbance (PROMIS-SD): Seltorexant led to an average reduction of 13.7 T-score on the Patient Reported Outcome Measurement Information System-Sleep Disturbance scale, suggesting improved sleep. The placebo group had an average reduction of 11.9 T-score.
- Depressive Symptom Response: 42.9% of patients taking Seltorexant achieved a significant response in their depressive symptoms based on the MADRS total score, compared to 36.3% of patients on placebo.
Probable Alzheimer's Disease
Another study (NCT05307692) investigated Seltorexant in participants with probable Alzheimer's disease. After 43 days, the drug demonstrated effects on agitation and aggression:
- Agitation (CMAI-C): Patients treated with Seltorexant showed an average reduction of 20.3 score on the Cohen-Mansfield Agitation Inventory-Community Version (CMAI-C), indicating decreased agitation. The placebo group had an average reduction of 17.5 score.
- Agitation and Aggression (NPI-C A+A): Seltorexant led to an average reduction of 13.4 score in the sum of agitation and aggression domain scores on the Neuropsychiatric Inventory Clinician Version (NPI-C A+A). Patients on placebo experienced an average reduction of 9.6 score.
- Sleep Disorder (SDI): On the Sleep Disorder Inventory (SDI) average total score, Seltorexant led to an average reduction of 0.5 score. The placebo group, however, showed a slightly greater average reduction of 0.8 score.
Currently Recruiting Trials
Participating in a clinical trial offers an opportunity to contribute to medical research and potentially access new treatments. Seltorexant is currently being studied in clinical trials to evaluate its effectiveness and safety for various conditions. These studies are crucial steps in understanding how new medications can help patients.
One significant study currently recruiting participants is "Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms," identified as NCT06559306. This is a Phase 3 trial, meaning it's one of the final stages of research before a potential new drug can be considered for approval. Sponsored by Janssen Research & Development, LLC, the study aims to understand how well Seltorexant works as an add-on therapy for individuals experiencing major depressive disorder who also have insomnia symptoms. The trial seeks to enroll approximately 752 participants.
The study is designed in two parts. In Part 1, participants will receive Seltorexant. Part 2 will then evaluate the safety and maintenance effect of Seltorexant compared to a placebo, as an adjunctive therapy to an existing antidepressant. This means Seltorexant would be taken alongside a participant's current antidepressant medication. The goal is to see if Seltorexant can improve depressive symptoms and help with insomnia in this patient group.
Where to Participate
The clinical trial for Seltorexant, NCT06559306, is actively recruiting across a wide geographic area, with sites in 22 states, covering 68 cities and 84 locations in total. This broad reach aims to make participation accessible to many eligible individuals.
Some of the cities with multiple participating sites include:
- Chicago, Illinois (3 sites)
- Tampa, Florida (3 sites)
- Miami, Florida (3 sites)
- Brooklyn, New York (2 sites)
- Charleston, South Carolina (2 sites)
- Las Vegas, Nevada (2 sites)
- Austin, Texas (2 sites)
- New York, New York (2 sites)
- Hialeah, Florida (2 sites)
- Houston, Texas (2 sites)
To be eligible for this study, participants must be between 18 and 74 years of age. The study is open to all genders. It is important to note that this trial is not for healthy volunteers; it is specifically for individuals diagnosed with major depressive disorder and insomnia symptoms. Children are not eligible to participate.
Development Timeline
The journey of Seltorexant in clinical development began with its first trial on February 19, 2018. Since then, Janssen Research & Development, LLC has consistently driven its research, sponsoring all 14 clinical trials conducted to date. This consistent sponsorship highlights a dedicated commitment to exploring Seltorexant's potential.
Initially, Seltorexant's development focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the research pipeline quickly expanded, reflecting a growing understanding of the drug's potential applications. Over time, studies began to investigate Seltorexant for a broader range of conditions, including abuse potential, Alzheimer's disease, and its effects in healthy non-dependent individuals and recreational sedative users. More recently, its potential in obstructive sleep apnea has also been explored.
The development has progressed through various phases, starting with 9 Phase 1 trials to assess safety and dosage, moving through 1 Phase 2 trial to evaluate effectiveness, and now advancing into 4 Phase 3 trials, which are crucial for confirming efficacy and safety in larger patient populations. Cumulatively, these trials have involved nearly 3,000 participants, with the latest trial initiated on August 19, 2024, marking continued progress in Seltorexant's development journey.