Solriamfetol + CBT-I for Insomnia

Overseen By Michael Perlis, PHD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Sleep aids, CNS active

Disqualifiers: Night shift, Renal issues, CAD, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well solriamfetol, a wakefulness-promoting medication, treats insomnia, either alone or combined with Cognitive Behavioral Therapy for Insomnia (CBT-I). The researchers seek to determine if staying awake longer can improve sleep quality and consistency. Suitable participants have experienced sleep difficulties for over six months, such as taking more than 30 minutes to fall asleep, waking multiple times at night, and feeling tired during the day. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Do I need to stop taking my current medications for the trial?

You will need to stop taking any medications that are used specifically to help you fall or stay asleep, such as trazodone, melatonin, or Tylenol PM. The trial does not specify other medication restrictions, but you should discuss your current medications with the trial team.

What is the safety track record for these treatments?

Research has shown that solriamfetol is generally well-tolerated. The FDA has already approved it for treating sleepiness caused by narcolepsy. However, like many medications, it can cause some side effects. Studies have reported common side effects such as trouble sleeping, headaches, nausea, reduced appetite, and anxiety in a small number of users.

Real-world data also suggests that some people experienced headaches and reduced appetite. Since solriamfetol can increase blood pressure, patients should have this monitored. Overall, the safety of solriamfetol is known and manageable for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Solriamfetol for insomnia because it offers a unique mechanism compared to typical sleep aids. Unlike traditional treatments that often depress the central nervous system, Solriamfetol works by enhancing wakefulness through dopamine and norepinephrine reuptake inhibition. This dual action could potentially lead to improved alertness during the day without the sedative effects seen in many sleep medications. Additionally, when combined with cognitive behavioral therapy for insomnia (CBT-I), it might offer a comprehensive approach that targets both the psychological and physiological aspects of insomnia.

What evidence suggests that this trial's treatments could be effective for insomnia?

Research has shown that solriamfetol can help people stay awake during the day, particularly those with conditions like sleep apnea that cause excessive sleepiness. It can also enhance alertness and thinking skills. Although solriamfetol has not been tested specifically for insomnia, it might improve sleep patterns by promoting daytime wakefulness. In this trial, some participants will receive solriamfetol alone, while others will receive it combined with Cognitive Behavioral Therapy for Insomnia (CBT-I), a proven method for improving sleep quality. Using solriamfetol alongside CBT-I might enhance these benefits by addressing both the mental and physical aspects of insomnia. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with Insomnia Disorder as per DSM-5, experiencing specific sleep disturbances more than three nights a week for over six months. They must have daytime impairment and prefer to sleep between 10 PM and 8 AM. Excluded are pregnant or breastfeeding individuals, those with unstable health conditions, no internet access, night shift workers, renal issues, severe heart disease or hypertension, other sleep disorders, using certain medications or substances.

Inclusion Criteria

I often feel very tired or sleepy during the day.

Participants will meet the diagnostic criteria for Insomnia Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

Must garner physician's assent from their primary care clinician

Exclusion Criteria

Night shift work

Planning to become pregnant, pregnant, and/or breastfeeding

Polysomnographic data indicating sleep disorders other than insomnia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive solriamfetol and/or CBT-I for insomnia treatment

12 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Therapy for Insomnia (CBT-I)
• Monitoring
• Placebo
• Solriamfetol

Trial Overview

The study tests the effectiveness of solriamfetol (a medication) alone and combined with Cognitive Behavioral Therapy for Insomnia (CBT-I). It aims to see if extending wakefulness can improve sleep quality. Participants will be monitored and may receive either the drug at a specified dose, CBT-I therapy sessions, placebo pills that contain no active drug or just monitoring without intervention.

How Is the Trial Designed?

Group I: Solriamfetol+ CBT-I Experimental Treatment 2 Interventions

Group II: Solriamfetol Only Experimental Treatment 2 Interventions

Group III: Placebo + CBT-I Active Control 2 Interventions

Group IV: Placebo Only Placebo Group 2 Interventions

Solriamfetol is already approved in United States for the following indications:

Approved in United States as Sunosi for:

• Excessive daytime sleepiness in patients with narcolepsy
• Excessive daytime sleepiness in patients with obstructive sleep apnea

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Axsome Therapeutics, Inc.

Industry Sponsor

Trials

34

Recruited

11,600+

Published Research Related to This Trial

Solriamfetol has been shown to significantly improve wakefulness in patients with narcolepsy and obstructive sleep apnea, with improvements of 7.65 to 10.14 minutes in narcolepsy and 4.5 to 12.8 minutes in OSA compared to placebo, based on data from 6 clinical trials involving both phase II and phase III studies.

The medication has a favorable safety profile, with fewer adverse effects and a lower risk of drug interactions compared to other treatments for excessive daytime sleepiness, making it a viable option for patients with narcolepsy and OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol for the Management of Excessive Daytime Sleepiness. Cuomo, MC., Sheehan, AH., Jordan, JK.[2022]

Solriamfetol is a new medication that effectively promotes wakefulness in adults with narcolepsy by selectively inhibiting the reuptake of dopamine and norepinephrine, as shown in clinical trials.

The drug was well tolerated by patients, with common side effects including headache, nausea, decreased appetite, insomnia, and anxiety, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy. Yang, J., Gao, J.[2020]

A 6-week randomized controlled trial will assess the effectiveness of voice-activated cognitive behavioral therapy for insomnia (CBT-I) in breast cancer survivors, who often experience insomnia at rates of 30-50%.

The study aims to compare the efficacy of this innovative delivery method against a sleep education control, with the primary outcome being the Insomnia Severity Index score, which will help determine if this approach can effectively reduce insomnia symptoms in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing delivery of components of cognitive behavioral therapy for insomnia to breast cancer survivors by smart speaker: a study protocol. Starling, CM., Greenberg, D., Zhou, E., et al.[2022]

Solriamfetol significantly improves excessive sleepiness in adults with narcolepsy and obstructive sleep apnea, as evidenced by increased mean sleep latency and reduced Epworth Sleepiness Scale scores in a meta-analysis of 1177 patients from five randomized controlled trials.

While solriamfetol is effective, it is associated with a higher risk of adverse events compared to placebo, although the risk of serious adverse events is not significantly different between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of solriamfetol for excessive sleepiness in narcolepsy and obstructive sleep apnea: findings from randomized controlled trials. Wang, J., Yang, S., Li, X., et al.[2021]

In a study involving 50 patients with obstructive sleep apnea (OSA), most physicians initiated solriamfetol at doses of 37.5 or 75 mg/day, with many patients adjusting to stable doses of 75 or 150 mg/day within a median of 14 days.

The primary reason for initiating solriamfetol was the need for better efficacy in managing excessive daytime sleepiness, and most patients (96%) remained stable on the medication at the time of data collection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol Titration and AdministRaTion (START) in Patients with Obstructive Sleep Apnea: A Retrospective Chart Review and Hypothetical Patient Scenario. Singh, H., Hyman, D., Parks, GS., et al.[2022]

In a posthoc analysis of two 12-week phase 3 studies involving 690 participants with narcolepsy or obstructive sleep apnea, solriamfetol significantly reduced excessive daytime sleepiness, with 30.5%-73.0% of participants achieving normal Epworth Sleepiness Scale scores (≤ 10) compared to placebo.

The safety profile of solriamfetol was similar for both narcolepsy and obstructive sleep apnea patients, with common side effects including headache and nausea, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically relevant effects of solriamfetol on excessive daytime sleepiness: a posthoc analysis of the magnitude of change in clinical trials in adults with narcolepsy or obstructive sleep apnea. Rosenberg, R., Baladi, M., Bron, M.[2022]

Solriamfetol (Sunosi™) is a newly approved oral medication in the USA that acts as a selective dopamine and norepinephrine reuptake inhibitor, specifically targeting excessive daytime sleepiness linked to narcolepsy and obstructive sleep apnoea.

The drug works by influencing the regulation of sleep-wake cycles through the dopaminergic and norepinephrine systems, addressing the underlying dysregulation that causes excessive sleepiness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol: First Global Approval. Markham, A.[2020]

Cognitive Behavioral Therapy for Insomnia (CBT-I) has been shown to significantly improve sleep quality and psychological outcomes in cancer patients and survivors, based on a review of 12 studies.

CBT-I not only enhances sleep but may also positively affect mood, fatigue, and overall quality of life, and it can be delivered through various methods to reach more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. Garland, SN., Johnson, JA., Savard, J., et al.[2022]

Cognitive behavioral therapy for insomnia (CBT-I) significantly improves sleep-related cognitions and insomnia severity in chronic heart failure patients, as shown in a study of 51 participants, with effects sustained for six months.

Changes in dysfunctional sleep-related beliefs were found to mediate the improvements in sleep quality and reductions in fatigue, depression, and anxiety, highlighting the importance of addressing these cognitions in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Cognitive Behavioral Therapy for Insomnia on Sleep-Related Cognitions Among Patients With Stable Heart Failure. Redeker, NS., Jeon, S., Andrews, L., et al.[2020]

A pilot study involving 30 Spanish-speaking breast cancer survivors showed that a 6-week eHealth Cognitive-Behavioral Therapy for Insomnia (CBT-I) intervention was highly acceptable and feasible, with excellent recruitment (95%) and retention (97%).

Post-treatment results indicated that CBT-I significantly improved insomnia symptoms, sleep disturbance, and sleep efficiency, with medium to large effect sizes, demonstrating its preliminary efficacy for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot randomized controlled trial of eHealth cognitive-behavioral therapy for insomnia among Spanish-speaking breast cancer survivors. Oswald, LB., Morales-Cruz, J., Eisel, SL., et al.[2023]

Cognitive-behavioral therapy for insomnia (CBT-I) has been proven effective in improving both short- and long-term outcomes for patients with uncomplicated and comorbid insomnia, indicating its strong efficacy as a treatment.

Future research on CBT-I should focus on enhancing treatment efficacy for clinically relevant outcomes, improving its effectiveness in community settings, and expanding training for practitioners to better disseminate the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of cognitive behavioral therapy for insomnia: what important research remains to be done? Vitiello, MV., McCurry, SM., Rybarczyk, BD.[2018]

Solriamfetol is a new drug being considered by the FDA to treat excessive sleepiness in patients with obstructive sleep apnea (OSA) and narcolepsy, showing promise as an effective adjunctive therapy based on results from three Phase 3 trials.

Unlike traditional stimulants, solriamfetol is well tolerated and does not cause adverse cardiac effects, rebound hypersomnia, or withdrawal symptoms, making it a safer alternative for managing sleepiness in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Solriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea. Abad, VC., Guilleminault, C.[2020]

Solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea showed long-term efficacy, with significant improvements in sleepiness scores and global impressions over a maintenance phase of up to 50 weeks.

The safety profile of solriamfetol was consistent with previous studies, with common side effects including headache and nausea, and no new safety concerns identified, although 9.5% of participants withdrew due to treatment-emergent adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea. Malhotra, A., Shapiro, C., Pepin, JL., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11868153/

SURWEY real-world study of solriamfetol: initiation, titration ...

A total of 27 patients (33%) reported an adverse event. The most frequent adverse events were headache (9%), decreased appetite (7%), and ...

2.

sunosi.com

sunosi.com/clinical-trial-results-sunosi

Clinical Results for Excessive Daytime Sleepiness (EDS) ...

*In a study, all 3 doses showed improved wakefulness through 9 hours at 12 weeks in people with OSA. At the beginning of the study, all groups had an ...

3.

journal.chestnet.org

journal.chestnet.org/article/S0012-3692(24)05470-9/fulltext

Results of the Solriamfetol's Effect on Cognitive Health in ...

Solriamfetol significantly improved cognitive function in patients with cognitive impairment associated with OSA and EDS. The overall ...

4.

jcsm.aasm.org

jcsm.aasm.org/doi/10.5664/jcsm.9384

Long-term effects of solriamfetol on quality of life and work ...

Study Impact: Long-term solriamfetol treatment was associated with sustained improvements in functional status, work productivity, and quality of life for up to ...

5.

sunosihcp.com

sunosihcp.com/sunosi-efficacy-excessive-daytime-sleepiness-osa

Efficacy for Excessive Daytime Sleepiness (EDS) Due to OSA

After 6 months, patients taking SUNOSI maintained reductions in daytime sleepiness compared to patients who worsened when switched to placebo.

6.

sunosi.com

sunosi.com/pi/sunosi.en.USPI.pdf

Prescribing Information

5.2 Psychiatric Symptoms. Psychiatric adverse reactions have been observed in clinical trials with SUNOSI, including anxiety, insomnia, and irritability [see ...

7.

sunosihcp.com

sunosihcp.com/safety-tolerability

SUNOSI safety and tolerability

Psychiatric adverse reactions have been observed in clinical trials with SUNOSI, including anxiety, insomnia, and irritability. Exercise caution when treating ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10913864/

A Comprehensive Review of Solriamfetol to Treat Excessive ...

The most common AEs included insomnia (23%), headache (16%), nausea (14%), decreased appetite (14%), diarrhea (11%) and anxiety (11%). In further studies, ...

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S2405844024144817

Post-marketing safety profile of solriamfetol: A real-world ...

A number of common AEs mentioned in FDA's prescribing information include headache, nausea, decreased appetite, insomnia, and anxiety.

10.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/sunosi

Sunosi | European Medicines Agency (EMA)

The safety profile was as expected for this type of medicine. Because the medicine could cause a harmful rise in blood pressure, patients should be monitored ...