A patient-reported outcomes study presented at SLEEP 2018 provides confirmatory real-world evidence of previously presented data showing the 7-hour action of REMfresh Ion-Powered Melatonin, a continuous release and absorption melatonin (CRA-melatonin). The product is 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 induces sleep onset and provides lasting and restorative sleep for up to 7 hours.
This new data shows a correlative relationship between a 7-hour Mesa Wave pharmacokinetic profile and real-world evidence of improvements in sleep duration, onset, maintenance, and sleep quality after taking REMfresh.
The post-marketing REMfresh Patient Reported Outcomes DURation (REMDUR) study was presented at SLEEP 2018.
In a sample of 500 patients on REMfresh responding to an online survey, 77.6% achieved 6 or more hours of sleep compared to 23.6% who slept that duration prior to taking REMfresh. A vast majority of respondents also reported a major or moderate improvement in sleep onset (91.6%), sleep maintenance (94.8%), and total sleep quality (97.2%). More than three-quarters (76.6%) of patients indicated they take REMfresh nightly. The proportion of patients reporting nightly CRA-melatonin use was significantly greater than the proportion of patients with less than nightly use. More than 98% of patients reported they were very likely or likely to continue taking REMfresh to treat their sleep complaints.
“The real-world evidence reported today in REMDUR provides further confirmation that REMfresh represents a significant advance in the use of melatonin as a baseline therapy for treating sleep complaints,” says David C. Brodner, MD, a 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, Fla, and senior medical advisor for Physician’s Seal LLC (makers of REMfresh), in a release . “It is no longer just a treatment for jet lag, but the CRA-melatonin found in REMfresh has been shown to provide substantial relief to individuals having nightly sleep challenges.”
REMDUR confirmed clinical trial findings from REMAKT (REM Absorption Kinetics Trial), a US-based randomized, crossover pharmacokinetic evaluation study in healthy, non-smoking adults that compared REMfresh with an immediate-release melatonin (IR-melatonin). The study results, 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 IR-melatonin. Conversely, the levels of the 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.
The REMfresh studies build upon the body of evidence from prolonged-release melatonin (PR-M), marketed in Europe, which demonstrated 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 absorption in the intestines, thereby extending the continual and gradual release pattern of melatonin through the night. There was a fast time to Cmax, 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.
Conventional melatonin products have had challenges at mimicking the profile of a Mesa Wave. The scientific work behind REMfresh sought to overcome these challenges by having the melatonin formulation in a matrix that maintains a patented, solubility-enhancing pH environment to help with the transport to the brush border of the gut and its subsequent absorption.
Designed as a hydrogel matrix tablet, REMfresh provides rapid release of the melatonin from the surface of the tablet, as the hydrogel release-controlling matrix is setting up in the acidic environment (pH of 1 to 3.5) in the stomach. As the tablet moves into the higher pH (5.5 to 6.5) environment of the small-intestine, which is above the pKa of melatonin (~4.0), the acidic moiety in the tablet is designed to maintain the pH within the tablet below 4.0 for 7+ hours. The hydrogel matrix, after proper hydration, allows continuous release of the active melatonin and acidic moiety into the lumen of 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.