Real-World Data From Surveillance Study Confirms Excellent Safety And Tolerability Profile Of REMfresh® Ion-Powered Melatonintm At 12 Months

BOCA RATON, Fla., July 23, 2018 /PRNewswire/ -- Physicians Seal, LLC^® (PS) today announced favorable results from its REMfresh^® Safety Update at 12 Months (REMSU-12) for REMfresh^® Ion-Powered Melatonin^tm, a real-world surveillance study reporting on the safety and tolerability profile of REMfresh^® (CRA-melatonin^tm). It is estimated that 87,467 individual patients used the product since the beginning of the surveillance. No serious adverse events were reported. Additionally, the self-reporting rates and patterns of non-serious adverse events were very low with only 15 events received. The two top-reported, non-serious adverse events were pruritis (2) and dizziness (2). The robust scientific literature on melatonin does not show that REMfresh^® (CRA-melatonin^tm) is known to cause any of these non-serious adverse events.

REMSU-12 captured and analyzed serious and non-serious adverse event reports for REMfresh^® (CRA-melatonin^tm) over a 12-month period from March 9, 2017 to March 9, 2018.

"The findings from REMSU-12 reaffirm the safety and tolerability profile of REMfresh^® (CRA-melatonin^tm) in real-world settings," 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^®. "This calculation results in an estimated 0.02 percent adverse event reporting rate for REMfresh^® (CRA-melatonin^tm), which is remarkably low.  More importantly, no pattern of next morning drug hangover was seen. This confirms the extremely benign side-effect profile of REMfresh^® seen in two prior studies."

REMfresh^® Ion-Powered Melatonin^tm is the first and only, continuous release and absorption melatonin^tm (CRA-melatonin^tm) to mimic the body's own 7-hour Mesa Wave^tm, the natural pattern of melatonin blood levels during a normal night's sleep cycle. This induces sleep onset and provides lasting and restorative sleep for up to 7 hours. Since REMfresh^® is not a drug, there is no drug hangover.

"REMfresh^® (CRA-melatonin^tm) 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 new therapies that will induce sleep and keep them asleep until the morning, without causing residual effects they'll feel the next day. With its unique delivery system that imitates the body's own natural sleep pattern, REMfresh^® has revolutionized the role of melatonin, when delivered in the CRA form. It is no longer just a treatment for jet lag, but the CRA-melatonin^tm found in REMfresh^® has been shown to provide substantial relief to individuals having nightly sleep challenges," said Dr. Brodner.

Nearly one-third of U.S. adults sleep less than the recommended seven hours daily.^1,2 Increasing evidence suggests an association between sub-optimal sleep duration and adverse health outcomes including a higher risk of diabetes, hypertension, heart attack, stroke, obesity and depression.³ A pooled analysis of 16 studies and over one million patients found short sleep duration corresponded with greater risk of morbidity and mortality.⁴

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. As people age, melatonin levels can drop by as much as 70 percent⁵ and their bodies may no longer produce enough melatonin to ensure adequate sleep.

Other available products, such as immediate-release melatonin, help initiate the onset of sleep but are usually unable to sustain prolonged sleep maintenance due to an immediate burst of melatonin, which is quickly degraded due to its relatively short half-life (60 minutes). Absorption in the lower digestive tract is limited by melatonin's limited ability to be absorbed in a low acidity or neutral pH environment.  

About REMSU-12
The REMfresh^® Safety Update at 12 Months (REMSU-12) report for REMfresh^® Ion-Powered Melatonin^tm is a real-world surveillance study reporting on the safety and tolerability profile of REMfresh^® (CRA-melatonin^tm) among 87,467  individual patients who used the product. Approximately 3.5 million REMfresh^® (CRA-melatonin^tm) caplets were sold in the U.S. during a 12-month period from March 9, 2017 to March 9, 2018.

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 12-month cluster analysis and trend analysis of adverse events reports received for REMfresh^® (CRA-melatonin^tm) was conducted by the same personnel.

The adverse events for this study were collected and processed from March 9, 2017 to March 9, 2018. An analysis of the data by reviewers showed that there were no reported serious adverse events associated with the use of REMfresh^® (CRA-melatonin^tm) during this time frame. A total of 15 non-serious adverse events were received. The two top-reported, non-serious adverse events were pruritis (2) and dizziness (2). The robust scientific literature on the widely used melatonin substance does not show that it is known to cause any of these non-serious adverse events.

About Non-Prescription REMfresh^®
REMfresh^® (CRA-melatonin^tm) is the first and only, continuous release and absorption formulation of UltraMel^® melatonin (available as 2 mg and 5 mg and with a 0.5 mg anticipated in the second half of 2018). UltraMel^® melatonin is a high-quality, 99 percent ultra-pure melatonin sourced from Western Europe exclusively for Physician's Seal^®.

REMfresh^® (CRA-melatonin^tm) 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. As with all supplements, individual results may vary.

REMfresh^® (CRA-melatonin^tm) is non-habit forming and does not contain narcotics, hypnotics, barbiturates, sedatives, antihistamines, alcohol or other harsh or additive chemicals. The usual adult recommended dose is 1-2 tablets 30-60 minutes before bedtime. Follow specific dosing instructions found on the back of the box for proper use of supplements.

REMfresh^® (CRA-melatonin^tm) is available at Walmart, Rite Aid and CVS/pharmacy. In 2017 REMfresh^® was ranked as  the #1 recommended brand for sleep management by sleep doctors⁶.  

REMfresh^® (CRA-melatonin^tm) was studied in a landmark, U.S.-based randomized, crossover pharmacokinetic (PK) evaluation study, called REMAKTtm (REM Absorption Kinetics Trial), in healthy, non-smoking adults that compared REMfresh^® (CRA-melatonin) with a market-leading, immediate-release melatonin (IR-melatonin). The study results, peer-reviewed and presented last year at SLEEP 2017, 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. SLEEP 2017 is the Annual Meeting of the Associated Professional Sleep Societies (APSS), LLC, a joint partnership of the American Academy of Sleep Medicine (AASM) and the Sleep Research Society (SRS).

Complete and final results from a real-world, observational study of 500 patients who took REMfresh^®  (CRA-melatonin^tm), called REMDUR (REMfresh^® Patient Reported Outcomes DURation) presented recently at SLEEP 2018, provides confirmatory real-world evidence of the previously peer-reviewed and presented REMAKTtm data showing the 7-hour action of REMfresh^®. This new data shows a correlative relationship between a 7-hour Mesa Wave^tm pharmacokinetic (PK) profile and real-world evidence of improvements in sleep duration, onset, maintenance and sleep quality after taking REMfresh^® (CRA-melatonin^tm). In a sample of 500 patients on REMfresh^® (CRA-melatonin^tm) responding to an online survey, 77.6 percent achieved 6 or more hours of sleep compared to 23.6 percent who slept that duration prior to taking REMfresh^® (p<.0001). A vast majority of respondents also reported a major or moderate improvement in sleep onset (91.6 percent, p<.0001), sleep maintenance (94.8 percent, p<.0001) and total sleep quality (97.2 percent, p<.0001). More than three-quarters (76.6 percent) of patients indicated they take REMfresh^® (CRA-melatonin^tm) nightly. The proportion of patients reporting nightly CRA-melatonin^tm use was significantly greater than the proportion of patients with less than nightly use (p<.0001). Most importantly, over 98 percent of patients reported they were very likely or likely to continue taking REMfresh^® (CRA-melatonin^tm) to treat their sleep complaints.

About Physician's Seal®
Physician's Seal^® is the innovator of REMfresh^®, the first and only continuous release and absorption, 99 percent ultra-pure melatonin^tm (CRA-melatonin^tm) that mimics the way the body naturally releases and maintains melatonin over a 7-hour period. Physician's Seal^®, 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 and connect with us on Facebook and You Tube.                   

Its sister subsidiary, IM HealthScience^® (IMH) is the innovator of IBgard^® and FDgard^® for the dietary management of Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD), respectively. In 2017, IMH added Fiber Choice^®, a line of prebiotic fibers, to its product line via an acquisition. IMH^® is a privately held company based in Boca Raton, Florida. It was founded in 2010 by a team of highly experienced pharmaceutical research and development and management executives. The company is dedicated to developing products to address overall health and wellness, including conditions with a high unmet medical need, such as digestive health. The IM HealthScience^® advantage comes from developing products based on its patented, targeted-delivery technologies called Site Specific Targeting^® (SST^®). For more information, visit www.imhealthscience.com to learn about the company, or www.IBgard.com,  www.FDgard.com, and www.FiberChoice.com.

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. You should not use this information for diagnosing a health problem or disease. 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.                     

¹ Ford, E.S., Cunningham, T.J., & Croft, J.B. (2015, May 1). Trends in Self-Reported Sleep Duration among US Adults from 1985 to 2012. Sleep, 38(5):829-832. doi: 10.5665/sleep.4684.
² Watson, N.F., Badr, M.S., Belenky, G., Bliwise, D.L., Buxton, G.M., Buysse, D.,...Tasali, E. (2015). Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society on the Recommended Amount of Sleep for a Healthy Adult: Methodology and Discussion. Journal of Clinical Sleep Medicine, 11(8):931-952. doi:10.1176/appi.ajp.158.11.1856.
³ Colten, H.R., & Altevogt, B.M. (Eds). (2006). Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem.  Institute of Medicine (US) Committee on Sleep Medicine and Research. Washington, DC: National Academies Press (US). doi: https://doi.org/10.17226/11617.
⁴ Cappuccio, F.P., D'Elia, L., Strazzullo, P.,&  Miller, M.A. (2010). Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep, 33(5):585-592
⁵ Zisapel, N. (2010). Melatonin and sleep. The Open Neuroendocrinology Journal, 3: 85-95.
⁶ Among primary care physicians with a certification in sleep disorders who recommended a brand of modified-release melatonin. Quintiles IMS ProVoice July-September 2017 survey.

SOURCE REMfresh