Physician’s Seal, LLC® Announces Data Analysis Plans for Ongoing Patient-Reported Outcomes (PRO) Studies Designed to Provide Confirmatory Real-World Evidence of Improvement in Sleep Duration and Sleep Quality for REMfresh®, the First and Continuous Release and Absorption Melatonin™ (Cra-Melatonin®)
- Ongoing PRO Study, REMfresh® Duration VALidation (REMVAL), will be analyzed upon study completion to assess improvement in sleep duration, onset, maintenance, quality and patient satisfaction in a general patient population. A second, ongoing study, REMfresh Short Sleep Cohort Assessment (REMSS) will assess improvements in sleep duration and maintenance among patients with chronic short sleep duration.
- Previously peer-reviewed and presented clinical study, REM Absorption Kinetics Trial (REMAKT), demonstrated REMfresh, a scientific breakthrough in sleep management with its continuous release and absorption, 99 percent ultra-pure melatonin (CRA-melatonin®), mimics the body’s own 7-hour Mesa Wave®, a natural pattern of melatonin blood levels during a normal night’s sleep cycle.
- Drug-free, nonprescription REMfresh ranks for a second year as the #1 recommended modified-release melatonin brand – and for the first year as the #1 recommended melatonin brand overall by primary care physicians with certification in sleep disorders.
Boca Raton, Fla.- (April 18, 2019) – Physician’s Seal, LLC®, innovators of REMfresh® (CRA-melatonin®), a clinically studied, drug-free, nonprescription sleep brand, today announced the data analysis plans for two significant patient- reported outcomes (PRO) studies related to the use of REMfresh® to treat occasional sleeplessness. REMfresh is the first and only continuous release and absorption melatonin™ (CRA-melatonin®) formulation to give patients up to 7 hours of sleep support.
It is anticipated that these two PRO studies will provide validation of a correlative relationship between REMfresh’s 7-hour Mesa-Wave pharmacokinetic (PK) profile and real-world evidence of improvement in sleep quality. PRO studies are being used more regularly by regulatory authorities and academia to provide real-world patient experiences in assessing a new technology or therapy.
The first ongoing study, REMfresh Duration VALidation (REMVAL), is designed to assess improvement in sleep duration, onset, maintenance, quality and patient satisfaction in a general patient population. The second ongoing study, REMfresh Short Sleep Cohort Assessment (REMSS), a cohort analysis of patients suffering with chronic short sleep duration (< 4 hours of sleep nightly), is designed to assess improvement in sleep duration and maintenance. The initial phase of these studies has reached the appropriate patient participation thresholds. Statistics & Data Corporation, a top-tier clinical data services provider, has independently determined that the number of participants in the study provides adequate power (>90%) to detect even small improvements in sleep outcomes. This high power, or probability of seeing statistically significant results if CRA-melatonin® is truly working to improve sleep outcomes, applies to the overall study population (REMVAL) as well as the cohort of short sleepers (REMSS). There will be an extended phase of recruitment to be completed no later than May 1, with all results to be peer-reviewed and presented at medical meetings later in 2019.
A previously peer-reviewed and presented pharmacokinetic (PK) evaluation study, REM Absorption Kinetics Trial (REMAKT), demonstrated REMfresh mimics the body’s own 7-hour Mesa-Wave® release profile, a natural pattern of melatonin blood levels during a normal night’s sleep cycle.
“Sleep research continues to be important because the cumulative effects of sleep loss are now becoming an important public health issue,” said David C. Brodner, M.D., a leading sleep specialist who is Double Board-Certified in Otolaryngology — Head and Neck Surgery as well as 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 continued, “Melatonin products have been used primarily as chronobiotics to address sleep disorders associated with abnormal timing of the circadian system, such as jet lag and shift work, but that is now fast changing. With its patented Ion Powered Pump® (IPP®) delivery system that mimics the body’s own natural sleep pattern, REMfresh may allow more individuals having trouble sleeping to experience drug-free, consistent, restorative sleep and have an improved quality of life with up to 7 hours of sleep support.”
“The clinical data on REMfresh, unveiled at the annual SLEEP medical meetings in 2017 and 2018, represented a significant advance in drug-free sleep maintenance therapy, an area of high unmet need,” said Dr. Brodner. “With the growing availability of nonprescription REMfresh nationwide, it is gratifying to see the remarkably strong patient satisfaction and “willingness to recommend” scores.
The results from these ongoing PRO studies are anticipated to provide further confirmatory real-world evidence of improvements in sleep duration and quality with the use of REMfresh.”
Value of Patient-Reported Outcomes Studies: Incorporate Patient Perspective
Increasingly, there is an appreciation by the U.S. Congress, regulatory authorities and academia, of the substantive value that real-world patient experience brings to assessing a new technology or therapy. In addition to the traditional randomized, placebo-controlled trial studies, regulatory authorities are now incorporating the patient perspective in their decision making, including PRO studies. A PRO study is a measurement based on a report that comes directly from the patient about the status or change in their health condition and without amendment or interpretation of the patient’s response by health-care intermediaries. PRO measures can be used to capture a patient’s everyday experience outside of the clinician’s office, and the effects of a treatment on the patient’s activities of daily living. Together, clinical measures and PRO measures can provide a fuller picture of patient benefit.
Chronic disorders of sleep and wakefulness affect an estimated 50-70 million adults in the United States. The cumulative long term effects of sleep loss have been associated with a wide range of damaging health consequences, including obesity, diabetes, impaired glucose tolerance, cardiovascular disease, hypertension, anxiety and depression.2 In terms of preventing health consequences, sleeping 6-8 hours per night consistently may provide optimal health outcomes.
Patient-Reported Outcomes (PRO) Study Design
These ongoing PRO studies are designed to obtain real-world evidence about patients’ sleep patterns, duration of sleep before and after REMfresh® (CRA-melatonin®), daily REMfresh use, onset of action, sleep maintenance, quality of sleep and overall satisfaction with REMfresh.
Patients with sleep disturbances in the general population who received a sample of CRA-melatonin (REMfresh) from their physicians were invited to complete a 13-question survey.
It is anticipated that the results of these studies should yield data that further validates the first PRO study, REMfresh® Patient Reported Outcomes DURation (REMDUR), that was peer-reviewed and presented at the annual medical meeting for sleep specialists, SLEEP 2018. The REMDUR study demonstrated that more than 77 percent of patients achieved 6 or more hours of sleep compared to 23.6 percent who slept that duration prior to taking REMfresh (p<.0001).
REMAKT Clinical Study Presented at Medical Congress
Pharmacokinetic data on REMfresh® was peer-reviewed and then presented in 2017 and 2018 at SLEEP, the Annual Meeting of the Associated Professional Sleep Societies LLC (APSS), and a joint meeting of the American Academy of Sleep Medicine (AASM) and the Sleep Research Society (SRS).
The study, REM Absorption Kinetics Trial (REMAKT), was a U.S.-based randomized, crossover pharmacokinetic (PK) evaluation study in healthy, non-smoking adults that compared REMfresh (CRA-melatonin) with a market-leading, immediate-release melatonin (IR-melatonin). The study found 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.
Analysis presented at SLEEP 2017 and 2018 showed that REMfresh builds upon the body of evidence from prolonged-release melatonin (PR-M), which demonstrated in well-conducted, placebo-controlled studies, statistically significant improvement in sleep quality, morning alertness, sleep latency and quality of life in patients aged 55 years and older compared with placebo. REMfresh was designed to overcome the challenges of continuous release and absorption in the intestines, thereby extending the continual and gradual release pattern of melatonin through the night (known as the Mesa Wave®, a flat-topped hill with steep sides. There was the desirable fast time to reach the sleep threshold level, which is anticipated to result in improved sleep onset, while the extended median plateau time to 6.7 hours and rapid fall-off in plasma levels at the end of the Mesa Wave may help to improve sleep maintenance and morning alertness.
Over 5,000 healthcare practitioners are estimated to have used REMfresh for their patients.
About Statistics & Data Corporation (SDC)
SDC delivers top-tier clinical trial services to pharmaceutical, biologic, and medical device/diagnostic companies since 2005. With strategic scientific consulting and clinical data services (biostatistics, data management/EDC, and IRT/IWRS) expertise at our core, our services are scalable via our diverse and complementary strategic partnerships to provide full service clinical trial solutions.
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 ultra-pure melatonin sourced from Western Europe exclusively for Physician’s Seal.
REMfresh caplets continuously release bioavailable, 99 percent ultra-pure melatonin over 7 hours, which may 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, acidic factors built inside the tablet maintain a lower pH within the tablet over 7 hours, to allow for continuous release and absorption of active melatonin into the intestines.
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. As with all supplements, individual results may vary.
REMfresh is non-habit forming and does not contain narcotics, hypnotics, barbiturates, sedatives, antihistamines, alcohol or other harsh additive chemicals. 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.
REMfresh is available at Walgreens, CVS, Rite Aid, Amazon.com/remfresh 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 ultra-pure melatonin (CRA-melatonin®) 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.
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 recurring indigestion), respectively. In 2017, 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.
1 U.S. Food and Drug Administration. Real World Evidence. Retrieved from https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence
U.S. Food and Drug Administration. 21st Century Cures Act. Retrieved from https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/21st-century-cures-act
2 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.
3 Cappuccio, F.P., D’Elia, L., Strazzullo, P., & Miller, M.A. (2010). Sleep duration and all-cause mortality: A systemic review and meta-analysis of prospective studies. Sleep, 33(5):585-592.
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.