Unprecedented 2-Year, Real-World Post-Marketing Surveillance Study For REMfresh®, The First And Only Drug-Free, Nonprescription Sleep Product That Mimics The Body's Own 7-Hour Mesa Wave, Now Peer-Reviewed And Accepted For Poster Presentation At Upcoming Sleep 2020, The World's Premier Sleep Conference

BOCA RATON, Fla., Aug. 6, 2020 /PRNewswire/ --

• REMfresh^® Safety Update at 24 Months (REMSU24) for REMfresh^® continuous release and absorption melatonin (CRA-melatonin^®) reconfirms excellent safety profile seen in REMSU12
• No serious adverse events for REMfresh reported during the two-year surveillance
• REMfresh is a patented, drug-free, nonprescription, #1 sleep doctor-recommended brand,¹ designed to achieve 7-hour sleep
• REMSU24 reconfirms the benign safety and tolerability profile observed in the peer-reviewed and published landmark clinical study,² REM Absorption Kinetics Trial (REMAKT), which demonstrated that REMfresh mimics the body's own 7-hour Mesa Wave^®, a natural pattern of melatonin blood levels during a normal night's sleep cycle

Physician's Seal, LLC^® (PS), innovators of REMfresh^® (CRA-melatonin^®), a clinically studied, drug-free nonprescription #1 sleep doctor-recommended melatonin sleep brand, today announced favorable results from its REMfresh^® Safety Update at 24 Months (REMSU24), which is now available on the SLEEP 2020 web site: https://www.sleepmeeting.org/wp-content/uploads/2020/06/34th_Annual_Meeting_of_the_Associated_Professional_Sleep_Societies_Abstract_Book_-_2020.pdf 

The peer-reviewed and published e-poster is entitled, "24-Month Post Marketing Safety Surveillance Data of a Novel Continuous Release and Absorption Melatonin (CRA-melatonin) Delivery System Confirms Favorable Safety Profile," (Abstract: 0471). The study's research abstract was published recently in an online supplement of the journal, Sleep. The findings also will be presented in August at Virtual SLEEP 2020, the 34^th annual meeting of the Associated Professional Sleep Societies LLC.       

REMSU24 is a real-world surveillance study reporting on the safety and tolerability profile of REMfresh in an estimated 320,255 individual patients who used the product as a purchased product during the two-year surveillance period. *

REMSU24 captured and analyzed serious and non-serious adverse event reports for REMfresh over a 24-month period from March 9, 2017 to March 9, 2019. No serious adverse events were reported. Additionally, the self-reporting rates and patterns of non-serious adverse events were very low with only 51 events recorded, a 0.016% event rate. The two most frequent, non-serious adverse events, headaches and nightmares, are known comorbidities of insomnia. The robust scientific literature on melatonin does not show that REMfresh is known to cause any of these non-serious adverse events and, in fact, these reported non-serious adverse events are often co-morbid conditions for people suffering from chronic sleeplessness.^3,4,5 

"The findings from REMSU24 are consistent with the outcome observed from REMSU12, which reaffirms the safety and tolerability profile of REMfresh in an extended and comprehensive real-world setting," said David C. Brodner, M.D., a leading sleep specialist who is Double Board-Certified in Otolaryngology -- Head and Neck Surgery and Sleep Medicine, Founder and Principle Physician at The Center for Sinus, Allergy, and Sleep Wellness, in Palm Beach County, Florida, and Senior Medical Advisor for Physician's Seal, LLC^®.

Dr. Brodner said, "This calculation results in an estimated 0.016 percent adverse event reporting rate for REMfresh, which is remarkably low. The outcome does not cause any concern for the safety profile of the product. This also confirms the benign safety and tolerability profile of REMfresh seen in prior studies and especially in the landmark REMAKT study² where REMfresh showed superiority over the leading marketed, conventional melatonin product. In fact, the scatter of these non-serious adverse events in REMSU24 probably cannot be separated from what could be expected in the general population. More importantly, no pattern of next-morning drug hangover was seen."

REMfresh is the first and only, continuous release and absorption melatonin, designed to mimic the body's own 7-hour Mesa Wave^®, the natural pattern of melatonin blood levels during a normal night's sleep cycle. This helps induce sleep onset and helps provide lasting and restorative sleep support for up to 7 hours. Since REMfresh is not a drug, there is no drug hangover.

Recent research demonstrates that sleep and the circadian system are strong regulators of immune function essentially contributing to the regulation of adaptive immunity.⁶  The study also shows that chronic sleep loss poses an enhanced risk for various diseases as a consequence of persistent low-grade systemic inflammation and immunodeficiency characterized by an enhanced susceptibility to infections, which have detrimental effects on health.⁶

REMfresh ranks for the third year as the #1 recommended modified-release melatonin brand, for the second year as the #1 recommended melatonin brand and for the first year as the #1 recommended nonprescription sleep aid brand overall by primary care physicians with certification in sleep disorders.¹

"REMfresh has been shown to be an effective drug-free solution that is now available to the millions of Americans in need of a good night's sleep, many of whom seek alternative therapies that will help induce sleep and keep them asleep until the morning, without causing residual effects they'll feel the next day. Delivered with its patented Ion Powered Pump^® (IPP^®) technology, that imitates the body's own natural sleep pattern, REMfresh is revolutionizing the role of melatonin. It is no longer just for jet lag, but the 99% ultrapure, CRA-melatonin found in REMfresh has been shown to provide substantial benefit to individuals having nightly sleep challenges," said Dr. Brodner.

Public Health Implications for Lack of Sleep
Chronic disorders of sleep and wakefulness affect an estimated 50-70 million adults in the United States.⁷ Long-term immune system consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome and type 2 diabetes.⁸ Evidence suggests that sleep disturbances may lead to health complications such as viral infections.⁹  Further, sleep disruption may also worsen the symptoms of some gastrointestinal disorders and increase the risk of certain cancers and death.⁸

Importantly, the public health implications are significant as nearly one-third of U.S. adults do not meet the recommended amount of sleep daily for adults of at least 7 hours.^10,11

Traditional treatments, including benzodiazepines, non-benzodiazepines, sedative antidepressants and non-prescription first-generation antihistamines, come with limitations in efficacy, safety and tolerability.¹² Importantly, prolonged use of prescription sleep aids may be associated with dependence, tolerance and withdrawal symptoms, including rebound insomnia.¹²

Additionally, results from a recent study suggest that 12% of older adults (greater than or equal to 65 years of age) use over the counter sleep medications.¹³ Many reported self-managing their sleep problems by taking over the counter diphenhydramine and/or doxylamine, which are not meant to be taken long term by individuals of any age and classified as potentially inappropriate for older adults.^13,14

Melatonin: The Body's Natural Sleep Ingredient
Melatonin is produced by the pineal gland in the brain and is the body's natural sleep ingredient. Melatonin levels normally begin to rise in the mid-to late evening and remain high for the majority of the night. Levels begin to decline towards early morning, as the body's wake cycle is triggered. Importantly, the decline in melatonin as people age may contribute to the common complaint of poor sleep quality amongst the elderly.¹⁵

Other available products, such as immediate-release melatonin, help initiate the onset of sleep but often are unable to sustain prolonged sleep maintenance. An explanation for this is that after the initial absorption in the stomach, the absorption of conventional melatonin may not be sustainable in the low acidity environment beyond the stomach.

Additionally, the melatonin absorbed from the stomach is rapidly metabolized due to melatonin's relatively short half-life (60 minutes). Continuous absorption in the lower digestive tract is limited by melatonin's limited ability to be absorbed in the low acidity or close to neutral pH environment beyond the stomach. This fundamental challenge for melatonin absorption is overcome in the case of patented REMfresh, which has a built-in low pH pump that is designed to keep ion-powered absorption going for seven hours.

About REMSU24
The REMfresh^® Safety Update at 24 Months (REMSU24) report for REMfresh^® is a real-world surveillance study reporting on the safety and tolerability profile of REMfresh^® among the estimated 320,255 individual patients who used the product.

An independent call center with pharmacovigilance-trained health care personnel in accordance with U.S. Food and Drug Administration (FDA) and global regulatory guidelines on properly reporting events was retained to receive and record REMfresh customer questions, product issues and adverse events. In addition, a 24-month cluster analysis and trend analysis of adverse events reports received for REMfresh (CRA-melatonin) was conducted by the same personnel.

About REMAKT
REM Absorption Kinetics Trial (REMAKT), a U.S.-based randomized, crossover pharmacokinetic (PK) evaluation study in healthy, non-smoking adults compared REMfresh (CRA-melatonin) with a market-leading, immediate-release melatonin (IR-melatonin). The study results, which were approved after peer-review and then published in Primary Care Companion for CNS Disorders² in August 2019, showed that melatonin levels with REMfresh exceeded the targeted sleep maintenance threshold for a median of 6.7 hours, compared with 3.7 hours with the leading IR-melatonin. Conversely, the levels of the market-leading IR-melatonin formulation dramatically increased 23 times greater than the targeted levels of exogenous melatonin for sleep maintenance and had a rapid decline in serum levels that did not allow melatonin levels to be maintained beyond 4 hours.

About REMDUR¹⁶ and REMVAL¹⁷
The 7-hour action of REMfresh together with its benign tolerability profile, has been validated by real-world, patient-reported outcomes (PRO) studies, REMfresh^® Patient Reported Outcomes DURation (REMDUR) and REMfresh Duration Validation (REMVAL). Additionally, REMfresh Short Sleep Cohort Assessment (REMSS)¹⁸ analyzed a cohort of 311 patients who reported sleeping four hours or less nightly, further establishing the sleep duration benefits of REMfresh in these high-risk patients. The cohort was derived from REMVAL. These studies, involving a total of over 1,600 patients, have been peer reviewed, accepted and then presented at SLEEP 2018 and SLEEP 2019, respectively, the Annual Meetings of the Associated Professional Sleep Societies (APSS), and a joint meeting of the American Academy of Sleep Medicine (AASM) and the Sleep Research Society (SRS).  These studies demonstrated significant user benefit in sleep onset, sleep duration and sleep quality when taking REMfresh.

About Nonprescription REMfresh^®     
REMfresh^® (CRA-melatonin^®) is the first and only, continuous release and absorption formulation of 0.5mg (Lite), 2 mg and 5mg (Extra Strength) UltraMel^® melatonin. UltraMel^® melatonin is a high-quality, 99 percent ultrapure melatonin sourced from an FDA DMF-approved facility in Western Europe exclusively for Physician's Seal.

REMfresh caplets, 99% ultrapure melatonin, continuously released and absorbed over 7 hours, is designed to help a person fall asleep faster, stay asleep longer and experience quality sleep, such as deep sleep and REM sleep.

REMfresh was designed as a hydrogel matrix tablet with its patented, scientifically advanced Ion-Powered Pump^® (IPP^®) technology, pioneered by Physician's Seal. Initially, there is a rapid release of the melatonin from the surface of the tablet in the acidic environment of the stomach. As the tablet moves into the higher pH of the small intestine, where melatonin is unlikely to dissolve, food grade organic acid built inside the tablet, helps maintain a lower pH within the tablet over 7 hours, to allow for continuous release and absorption of active melatonin throughout the GI tract.  

REMfresh is a dietary supplement and is regulated under the Federal Dietary Supplement Health and Education Act, which does not require pre-approval. Melatonin has been in common use for over two decades and has a well-established profile of safe use by millions of people around the world. Physicians note that melatonin has an advantage compared to many sleep drugs when it comes to morning dysfunction, drowsiness, or unusual night occurrences such as sleepwalking.  

REMfresh is non-habit forming and does not contain narcotics, hypnotics, barbiturates, sedatives, antihistamines or alcohol. The usual adult recommended dose is 1-2 tablets 30-90 minutes before bedtime. Specific dosing instructions found on the back of the box should be followed for proper use of supplements. REMfresh is available in 0.5mg (Lite), 2mg and 5mg (Extra Strength) versions.

Over 5,000 healthcare practitioners are estimated to have used REMfresh for their patients.

REMfresh is available at Walgreens, CVS, Rite Aid, select Walmart stores, Target, Kroger, Meijer, Amazon.com and www.REMfresh.com.

About Physician's Seal^® 
Physician's Seal^® is the Innovator of REMfresh^®, the first and only continuous release and absorption, 99 percent ultrapure melatonin (CRA-melatonin^®), that mimics the way the body naturally releases and takes up melatonin over a 7-hour period. Physician's Seal (PS), founded in 2015, is a privately held company based in Boca Raton, Florida. It is committed to bringing cutting-edge life science applications to doctors and their patients. For more information, visit www.REMfresh.com.

Physician's Seal's sister subsidiary, IM HealthScience^® (IMH), is the innovator of the two medical foods IBgard^® and FDgard^® for the dietary management of Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD or meal-triggered indigestion), respectively. IMH rounds out its line of digestive products with Fiber Choice^®, a well-known, natural prebiotic chewable daily fiber that helps support regularity. IMH^® is a privately held company based in Boca Raton, Florida. It was founded in 2010 by a team of highly experienced pharmaceutical executives. Both PS and IMH are dedicated to developing products to address overall health and wellness in digestive health and sleep. The Physician's Seal and IM HealthScience advantage comes from developing products based on patented, targeted-delivery technologies, including IPP^® (Ion-Powered Pump^®) and SST^® (Site Specific Targeting^®) technologies. For more information, visit www.imhealthscience.com to learn about the company, or www.IBgard.com, www.FDgard.com and www.FiberChoice.com.

* Future analysis will include the estimated number of patients who consumed REMfresh samples received from physicians.

References:

¹ Among primary care physicians with a certification in sleep disorders who recommended a brand of melatonin. IQVIA ProVoice Feb.-March 2020 survey.

² Seiden, D.J., & Shah, S.M. A Randomized, Crossover, Pharmacokinetics Evaluation of a Novel Continuous Release and Absorption Melatonin Formulation. Primary Care Companion for CNS Disorders 2019. doi: https://doi.org/10.4088/PCC.19m02450

³ Tran D.P and Spierings E.L. (2013) Headache and insomnia: their relation reviewed; Cranio. Jul; 31(3): 165-70.

⁴ Schlarb A.S. et.al. (2015) Nightmares and Associations with Sleep Quality and Self-Efficacy among University Students; J. Sleep Disorders and Management; 1:1.

⁵ Kim S.K. et. al. (2018) Relationship between sleep quality and dizziness; PLoS One. 13(3): e0192705.

⁶ Besedovsky, L, et. al. (2012) Sleep and immune function. Plfugers Arch. 463(1); 121-137

⁷ Institute of Medicine (US) Committee on Sleep Medicine and Research; Colten HR, Altevogt BM, eds. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington, DC: National Academies Press; 2006.

⁸ Goran M, Wille M, Hemels, MEH. (2017) Short- and long-term consequences of sleep disruption, Nat Sci Sleep, 9: 151-161.

⁹ Ibarra-Coronado EG, et al. (2015) The bidirectional relationship between sleep and immunity against infections, J Immunol Res 678164.

¹⁰ Watson NF, Badr MS, Belenky G, et al. (2015) Joint consensus statement of the American Academy of Sleep Medicine and the Sleep Research Society on the recommended amount of sleep for a healthy adult: methodology and discussion; J Clin Sleep Med 11(8): 931-52.

¹¹ Nugent CN, Black LI. (2016) Sleep duration, quality of sleep, and use of sleep medication, by sex and family type, 2013-2014. US Department of Health and Human Services, CDC, National Center for Health Statistics. No. 230, January.

¹² Spadoni G, Bedini A, et al. (2015) Pharmacokinetic and pharmacodynamic evaluation of ramelteon: an insomnia therapy. Expert Opin Drug Metab Toxicol. 11(7): 1145-1156.

¹³ Olufunmilola A, Schleiden L, Albert, SM. (2017) Over-the- counter medications containing diphenhydramine and doxylamine used by older adults. Int J Clin Pharm, 39(4):806-817.

¹⁴ 2015 Beers Criteria Update Expert Panel, American Geriatrics Society 2015 Update. Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatrics Society.

¹⁵ Zisapel, N (2010) Melatonin and sleep. The Open Neuroendocrinology Journal. 3:85-95

¹⁶Seiden, D.J., Brodner, D.C., & Shah, S.M. (2018). Improvement in Sleep Maintenance and Sleep Quality with Ion Powered Pump Continuous Release and Absorption Melatonin: Results from a Self-Reported Patient Outcomes Study. (Abstract 0419). Poster Presented at SLEEP 2018, Baltimore, Maryland.

¹⁷ Brodner, D.C., Seiden, D.J., & Shah, S.M. (2019). Observed Hypnotic Effects with a Continuous-Release Ion Powered Pump Melatonin Delivery System: Self-Reported Patient Outcomes Study Results Demonstrating Improvement in Sleep Duration and Quality. (Abstract 0399). Poster Presented at SLEEP 2019, San Antonio, Texas.

¹⁸ Seiden, D.J., Brodner, D.C., & Shah, S.M. (2019) Improvement in Sleep Duration and Maintenance with Ion Powered Continuous Release and Absorption Melatonin in a Cohort of Patients with Chronic Short Sleep Duration: Results from a Patient-Reported Outcomes Study. (Abstract 0398). Poster Presented at SLEEP 2019, San Antonio, Texas.

Copyright © 2020 REMfresh^® This information is for educational purposes only and is not meant to be a substitute for the advice of a physician or other health care professional. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.  You should not use this information for diagnosing a health problem or disease. REMfresh is intended to relieve occasional sleeplessness.   Statements made in this release rely upon reviews of literature, input from PS's advisors and PS's own expertise. There may always be other opinions or emphasis points. Some of the statements from different sources may not mesh with each other. There may be inadvertent inaccuracies that PS is not aware of. Space limitations in this release only allow limited reference to some guidelines or practices which may, or may not, be fully agreed to by all scientific, medical or regulatory experts. For any of PS's products this release does not make or have any intent to make drug claims or any comparison or implied claims against FDA approved interventions for sleep disorders. Any comments on any products are based on literature reviews and input from PS's own advisors. There may be others who have other points of view. Pre-clinical findings do not always correlate with clinical or real-world findings. The reader is urged to check all current information, including the latest website disclosures and/or package inserts, of any of the medical products mentioned here, as information, including government regulations, changes all the time. The statements of individual opinions are those of the individuals quoted and do not necessarily reflect opinions of PS. Please fully read all disclaimers/clarifications/explanations. PS disclaims any injury or alleged injury resulting from any ideas, methods, instructions or products referred to here. Health care practitioners should use their independent, professional judgment in helping their patients best manage their sleep conditions. The company will strive to keep information current and consistent but may not be able to do so at any specific time. Generally, the most current information can be found on www.REMfresh.com. Individual results may vary.

REMfresh is protected by U.S. Patents No.: 8,691,275; 9,186,351; 9,241,926; 9,549,900, 10,226,447.  Keep out of reach of children. Store at room temperature. Individual results may vary.  Do not use if blister is torn or ripped or if there is any other evidence of tampering. Consult a physician if using any supplement for the first time. Please read package insert and the website for more information.

SOURCE Physician's Seal

Related Links

http://www.REMfresh.com