Suvorexant for Sleep Disturbances in PSP

Recruiting in Palo Alto (17 mi)

Overseen by Thomas Neylan, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of California, San Francisco

Must not be taking: Benzodiazepines, Sedating antipsychotics

Disqualifiers: Pregnancy, Major psychiatric disorder, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests two medications, suvorexant and zolpidem, on people with PSP who have severe sleep issues. Suvorexant helps block wakefulness signals to improve sleep, while zolpidem boosts sleep signals to help people fall asleep. The study aims to see if these medications can safely improve sleep and well-being.

Do I have to stop taking my current medications to join the trial?

You need to stop taking sleep-modifying medications for 1 week before starting the study and cannot take them during the 6-week study. Other medications must be stable for 4 weeks before starting the study.

What data supports the idea that the drug Suvorexant for Sleep Disturbances in PSP is an effective treatment?

The available research does not provide any data on Suvorexant for Sleep Disturbances in PSP. The articles focus on other conditions and treatments, such as sleep-disordered breathing and prostate cancer therapies, but do not mention Suvorexant or its effectiveness for sleep disturbances in PSP. ^{1 2 3 4 5}

What safety data exists for Suvorexant for sleep disturbances in PSP?

The provided research does not contain any safety data for Suvorexant or its other names (Belsomra, MK-4305, MK4305, Zolpidem, Ambien) related to sleep disturbances in PSP. The studies focus on bisphosphonates like zoledronic acid and their effects in multiple myeloma and other conditions, which are unrelated to Suvorexant. ^{6 7 8 9 10}

Is the drug Suvorexant a promising treatment for sleep disturbances in PSP?

Yes, Suvorexant is a promising drug for sleep disturbances because it helps people fall asleep faster and stay asleep longer. It is approved by the FDA for treating insomnia and has shown positive effects on sleep quality in various studies. ^{11 12 13 14 15}

Research Team

Thomas Neylan, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with Progressive Supranuclear Palsy (PSP) who have stable medications, a caregiver, and can comply with study requirements. Participants must not be on sleep-modifying meds prior to the study or have conditions that could affect safety/data quality.

Inclusion Criteria

You have been diagnosed with PSP by participating in certain research studies or by providing evidence of an accurate diagnosis to the study doctor.

Be willing to maintain a stable sleeping environment and their typical daily schedule for the duration of the 6-week study

I haven't taken any sleep medications for the last week.

Exclusion Criteria

I am not taking sleep-affecting medications or can stop them for 7 weeks.

I have diabetes that requires insulin.

You have a history of intellectual disability.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a double-blind, within-subject trial with three conditions: suvorexant, zolpidem, and placebo, each lasting 1 week, separated by a 1-week washout period.

6 weeks

Remote monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo oral capsule (Other)
• Suvorexant (Other)
• Zolpidem (Other)

Trial Overview The trial tests if suvorexant or zolpidem improves sleep in PSP compared to a placebo. It's a double-blind study where each treatment lasts one week with washout periods in between. Sleep patterns and daytime symptoms are measured to assess effectiveness.

Participant Groups

Group I: Zolpidem Arm Active Control 1 Intervention

Participants will be given one week of Zolpidem.

Group II: Suvorexant Arm Active Control 1 Intervention

Participants will be given one week of Suvorexant.

Group III: Placebo Arm Placebo Group 1 Intervention

Participants will be given one week of a placebo pill.

Suvorexant is already approved in Japan for the following indications:

Approved in Japan as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

US Department of Veterans Affairs

Collaborator

Trials

881

Recruited

502,000+

Kameron Leigh Matthews

US Department of Veterans Affairs

Chief Medical Officer since 2021

MD from Johns Hopkins University

Doug Collins

US Department of Veterans Affairs

Secretary of Veterans Affairs

BA in Political Science from North Georgia College & State University

Findings from Research

Positive airway pressure (PAP) therapy is the gold standard for treating sleep-disordered breathing, significantly reducing apnea-hypopnea index (AHI) and improving patient quality of life, but many patients struggle with adherence due to discomfort.

Emerging treatments like the hypoglossal nerve stimulator and phrenic nerve stimulator offer promising alternatives by directly stimulating nerves to alleviate airflow obstruction and stabilize breathing patterns, respectively, thus improving AHI severity and quality of life for patients with obstructive and central sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Treatment of Sleep-Disordered Breathing. Lou, BX., Greenberg, H., Korotun, M.[2021]

Abiraterone, enzalutamide, and radium-223 have been shown to significantly improve both radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC), based on phase 3 clinical trials.

Each treatment has distinct adverse effects: enzalutamide increases the risk of seizures, abiraterone can lead to mineralocorticoid excess, and radium-223 is associated with myelosuppression, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy Update for Metastatic Castration-Resistant Prostate Cancer. Dinh, JA., Baker, D., Chahal, M.[2017]

In a Phase I trial of suramin for hormone-refractory prostate cancer, 22% of patients on low doses and 32% on high doses experienced adrenal cortical insufficiency, indicating a dose-dependent risk of glucocorticoid and mineralocorticoid insufficiency.

Long-term glucocorticoid insufficiency was observed in 20% of patients tested more than 90 days after stopping suramin, suggesting that patients on high doses should receive appropriate hormone replacement therapy to manage potential adrenal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mineralocorticoid insufficiency due to suramin therapy. Kobayashi, K., Weiss, RE., Vogelzang, NJ., et al.[2019]

In a study of 1052 patients with metastatic castration-sensitive prostate cancer, apalutamide combined with androgen-deprivation therapy significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo plus ADT.

While apalutamide exposure did not correlate with improved survival outcomes, higher exposure levels were linked to an increased risk of skin rash and pruritus, suggesting that dose adjustments may be beneficial to manage these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study. T'jollyn, H., Ackaert, O., Chien, C., et al.[2022]

In a study of 22 patients with high-risk metastatic hormone-sensitive prostate cancer, treatment with abiraterone acetate plus androgen deprivation therapy (AAP + ADT) resulted in significantly longer prostate-specific antigen progression-free survival (PSA-PFS) compared to combined androgen blockade (CAB), with PSA-PFS not reached in the AAP group versus 15.1 months in the CAB group.

The AAP group also achieved lower serum PSA levels more quickly, with times to reach PSA ≤0.2 ng/ml and ≤0.1 ng/ml being significantly shorter than in the CAB group, indicating that AAP may offer better clinical efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of Abiraterone Acetate Plus Prednisolone and Combined Androgen Blockade in High-risk Metastatic Hormone-Sensitive Prostate Cancer]. Yasukawa, H., Ikehata, Y., Tsuboi, Y., et al.[2021]

In a study involving 1960 patients with newly diagnosed multiple myeloma, both zoledronic acid (ZOL) and clodronate (CLO) were found to be well tolerated over a median follow-up of 5.9 years, with similar rates of acute renal failure between the two treatments.

The incidence of osteonecrosis of the jaw (ONJ) was low overall but significantly higher in the ZOL group (3.7%) compared to the CLO group (0.5%), indicating a potential safety concern with ZOL, particularly after dental procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results. Jackson, GH., Morgan, GJ., Davies, FE., et al.[2022]

In a phase III trial involving 308 patients with untreated high-risk multiple myeloma, zoledronic acid significantly improved both overall survival (67% vs. 48%) and progression-free survival (66% vs. 52%) compared to the control group after a median follow-up of nearly 70 months.

The treatment was well tolerated, with no reported cases of renal impairment or osteonecrosis of the jaw, indicating that zoledronic acid can be safely integrated into the treatment regimen for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation. Avilés, A., Neri, N., Huerta-Guzmán, J., et al.[2021]

In a study of 1126 patients with metastatic bone disease, zoledronic acid (ZOL) showed a significant improvement in overall survival for 38% of patients with elevated baseline NTX levels, indicating its potential effectiveness in advanced cases.

While ZOL did not show a general survival advantage across all patients, its benefits were particularly noted in those with aggressive disease characteristics, suggesting that ZOL may be especially beneficial for patients with advanced metastatic bone disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features-An exploratory analysis of placebo-controlled trials. Coleman, RE., Lipton, A., Costa, L., et al.[2022]

In a study of 1,655 multiple myeloma patients, those treated with zoledronic acid (ZOL) experienced significantly lower rates of skeletal-related events (SREs) and mortality compared to those who did not receive bisphosphonate therapy.

Patients who maintained longer treatment persistency with ZOL (≥1.5 years) had a much lower incidence of SREs and fractures, highlighting the importance of consistent treatment for maximizing clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistency with zoledronic acid is associated with clinical benefit in patients with multiple myeloma. Henk, HJ., Teitelbaum, A., Perez, JR., et al.[2018]

The combination of estramustine phosphate (EMP) at 900 mg/m2 and paclitaxel at 225 mg/m2 is well tolerated in women with solid tumors, with significant antitumor activity observed against breast and ovarian cancers.

The maximum-tolerated dose was identified as EMP 1,200 mg/m2, which caused severe side effects like nausea and vomiting, leading to the use of a lower dose (900 mg/m2) in further studies without affecting paclitaxel pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacologic study of estramustine phosphate and short infusions of paclitaxel in women with solid tumors. Garcia, AA., Keren-Rosenberg, S., Parimoo, D., et al.[2017]

This trial will assess the efficacy of suvorexant, an FDA-approved sleep aid, in reducing nighttime wakefulness and delirium in 120 older cardiac surgery patients in the ICU.

The study aims to determine if suvorexant can improve sleep quality and reduce the incidence of postoperative delirium, which is important for recovery in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. Azimaraghi, O., Hammer, M., Santer, P., et al.[2021]

Suvorexant, an orexin receptor antagonist, significantly improved sleep parameters in healthy young men, with all doses (10 mg, 50 mg, and 100 mg) showing better sleep compared to placebo, particularly in reducing the time to persistent sleep and wake after sleep onset.

While suvorexant was generally well tolerated, higher doses (50 mg and 100 mg) showed some next-day residual effects, such as reduced alertness and slower reaction times, indicating a need for careful dosing in potential therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sun, H., Kennedy, WP., Wilbraham, D., et al.[2022]

Suvorexant, the first orexin receptor antagonist approved by the FDA for treating insomnia, has been shown to effectively induce and maintain sleep in adult and elderly patients over treatment periods of up to 12 months.

While the FDA approved doses of 5, 10, 15, and 20 mg due to concerns about safety and next-morning effects like somnolence and unusual behaviors, suvorexant represents a novel approach to insomnia treatment, potentially leading to new therapies targeting orexin receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. Jacobson, LH., Callander, GE., Hoyer, D.[2015]

Suvorexant (Belsomra®) is a new sleep medication that works by blocking orexin neurons, leading to a rapid onset of sleep, and is effective at a prescribed dose of 10 mg before bedtime.

A highly sensitive urine assay was developed to accurately identify and quantify suvorexant, demonstrating excellent precision and stability, which is crucial for monitoring its use due to potential misuse and interactions with other sedatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). Sullinger, S., Bryand, K., Kerrigan, S.[2017]

Suvorexant, a dual orexin receptor antagonist approved for insomnia, is primarily metabolized in the body with 90% of its radioactivity recovered after administration, indicating effective absorption and elimination.

The drug mainly inhibits CYP3A4 and CYP2C19 enzymes but is unlikely to cause significant drug interactions at clinical doses due to low plasma concentrations, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans. Cui, D., Cabalu, T., Yee, KL., et al.[2017]

References

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

Advances in Treatment of Sleep-Disordered Breathing. [2021]

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

Therapy Update for Metastatic Castration-Resistant Prostate Cancer. [2017]

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

Mineralocorticoid insufficiency due to suramin therapy. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[Comparison of Abiraterone Acetate Plus Prednisolone and Combined Androgen Blockade in High-risk Metastatic Hormone-Sensitive Prostate Cancer]. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features-An exploratory analysis of placebo-controlled trials. [2022]

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

Persistency with zoledronic acid is associated with clinical benefit in patients with multiple myeloma. [2018]

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

Phase I and pharmacologic study of estramustine phosphate and short infusions of paclitaxel in women with solid tumors. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. [2021]

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

Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. [2015]

14. England pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). [2017]

15. England pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans. [2017]