Circadin (melatonin prolonged release) / Lundbeck, Neurim, Flynn Pharma, Insud Pharma, Biocodex, Kuhnil Pharma, Teva - LARVOL DELTA

Oral Melatonin VS Nebulized Dexmedetomidine Premedication on Attenuation of Hemodynamic Response to Direct Laryngoscopy and Tracheal Intubation in Hypertensive Patients (clinicaltrials.gov) - P2/3 | N=70 | Not yet recruiting | Sponsor: Tanta University

Intubation • New P2/3 trial

The revival of the mini-tablets: Recent advancements, classifications and expectations for the future. (PubMed, Eur J Pharm Biopharm) - "Most recently, two novel products with different concepts were authorized by the EMA and entered the market which are highlighted in this review: the first orodispersible mini-tablet with enalapril maleate for congenital heart failure (Aqumeldi® from Proveca Pharma) and the first single unit mini-tablet with matrix-type controlled melatonin release for insomnia (Slenyto® from Neurim Pharmaceuticals)...Film-coatings enabling gastric resistance, taste masking or sustained-release properties have been realized in both fluid-bed and drum coaters using the same polymers as for conventional tablets. There is still a significant lack in regulatory guidance despite the recent success of the mini-tablet concept, starting from suitable characterization methods in the pharmacopoeias up to the design and conduct of clinical studies on mini-tablets."

Journal • Review • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Insomnia • Sleep Disorder

Mela-Nia: A Novel Inhaled Formulation of Melatonin to Treat Adults with Insomnia: Pharmacokinetic Study (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Woolcock Institute of Medical Research

New P1 trial • CNS Disorders • Insomnia • Sleep Disorder

Mela-Nia: A Novel Inhaled Formulation of Melatonin to Treat Adults with Insomnia: Efficacy Study (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Woolcock Institute of Medical Research

New P1 trial • CNS Disorders • Insomnia • Sleep Disorder • Aβ42 • BDNF • CRP • GFAP • IL6 • NEFL

The Basel BOMP-AID Randomized Trial (clinicaltrials.gov) - P4 | N=190 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • CNS Disorders

Comparing Two Doses of Oral Melatonin as Premedication in Children Undergoing Surgery (clinicaltrials.gov) - P=N/A | N=120 | Recruiting | Sponsor: Al-Azhar University | Not yet recruiting ➔ Recruiting

Enrollment open • Surgery • Psychiatry

Comparing Two Doses of Oral Melatonin as Premedication in Children Undergoing Surgery (clinicaltrials.gov) - P=N/A | N=120 | Not yet recruiting | Sponsor: Al-Azhar University

New trial • Surgery • Psychiatry

Cognitive Behavioral Therapy and Multimodal Therapy in Treating Sleep Disturbance in Patients With Cancer (clinicaltrials.gov) - P2 | N=68 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2028 ➔ Dec 2025 | Trial primary completion date: Jun 2028 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Sleep Disorder • Solid Tumor

In vitro Modified Release Studies on Melatoninergic Fluorinated Phenylalkylamides: Circumventing their Lipophilicity for Oral Administration. (PubMed, Curr Pharm Des) - "Moreover, a number of these derivatives were proven suitable for dealing with sleep onset problems, whilst others for dealing with combined sleep onset/sleep maintenance dysfunctions."

Journal • Preclinical • Sleep Disorder

Melatonin in Obese Patients in Laparoscopic Cholecystectomy (clinicaltrials.gov) - P=N/A | N=60 | Not yet recruiting | Sponsor: Ain Shams University

New trial • Anesthesia • Obesity • Pain

Melatonin treatment has consistent but transient beneficial effects on sleep measures and pain in patients with severe chronic pain: the DREAM-CP randomised controlled trial. (PubMed, Br J Anaesth) - "Circadin™ treatment did not improve sleep disturbance in patients with severe chronic pain compared with placebo at 6 weeks, but there were consistent improvements in aspects of sleep in the shorter term. Given its favourable safety profile, it could be beneficial for some patients with chronic pain."

Journal • CNS Disorders • Fibromyalgia • Musculoskeletal Pain • Oncology • Pain • Rheumatology • Sleep Disorder

Identification of Cyclocybe erebia metabolites that affect the circadian rhythm of Eluc expression under control of Bmal1 promoter in mouse fibroblast cells. (PubMed, J Biosci Bioeng) - "Compounds 1 and 2 were named cyclocircadins A and B, respectively. These findings suggested that natural diterpenoids could be a source of compounds with the activity affecting circadian rhythms."

Journal • Preclinical • CNS Disorders • Metabolic Disorders • Sleep Disorder • ARNTL

Cognitive Behavioral Therapy and Multimodal Therapy in Treating Sleep Disturbance in Patients With Cancer (clinicaltrials.gov) - P2 | N=68 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2023 ➔ Jun 2028 | Trial primary completion date: Jun 2023 ➔ Jun 2028

Trial completion date • Trial primary completion date • CNS Disorders • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Sleep Disorder • Solid Tumor

Potent Lipophilic Melatoninergic x-fluoro-y-methoxy Substituted Phenylalkylamides: Molecular Dynamics Calculations and in vitro Modified Release in Aqueous Media from Tablet Formulations. (PubMed, Curr Pharm Des) - "Apart from the nature and relevant content of the formulants used, this bimodal release profile of the new analogues depends, to a large extent, on the diverse structural arrangement of their side chains in space, as nicely demonstrated by the molecular dynamics calculations, conducted in the context of this study."

Journal • Preclinical • Sleep Disorder

Correction EQL Pharma enters into license agreement with large pharmaceutical company in Turkey for Mellozzan (melatonin) [Google translation] (Cisionwire) - "EQL has entered into an exclusive license agreement for its product Mellozzan (melatonin) with a major pharmaceutical company for sales in Turkey and Kazakhstan. 'EQL has previously signed license agreements with parties for a number of countries, but this is a milestone as it is our first agreement with the sale of one of our products outside the borders of Europe,' says Axel Schörling, CEO at EQL Pharma."

Licensing / partnership • CNS Disorders

The utility of melatonin for the treatment of sleep disturbance following traumatic brain injury: A scoping review. (PubMed, Arch Phys Med Rehabil) - "Melatonin has good tolerability after short-term use and the potential to be a therapeutic agent for those with sleep disturbance following TBI. Melatonin was shown to be beneficial to sleep quality, sleep duration and sleep efficiency. Additional clinically relevant outcomes of improved mental health suggest that melatonin use may be a promising treatment option for individuals experiencing co-occurring disorders of mood and sleep disturbance post-injury."

Journal • Review • CNS Disorders • Fatigue • Insomnia • Psychiatry • Sleep Disorder • Vascular Neurology

Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects (clinicaltrials.gov) - P4 | N=0 | Withdrawn | Sponsor: Institution de Lavigny | Unknown status ➔ Withdrawn

Trial withdrawal • CNS Disorders • Epilepsy

Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. (PubMed, Expert Rev Clin Pharmacol) - "Melatonin is rapidly absorbed and undergoes first pass hepatic metabolism by cytochrome CYP1A2; over 80% is excreted in the urine as 6-sulfatoxymelatonin (inactive). Immediate-release melatonin (IRM) is short-acting (3-4 hours), whereas PRM provides therapeutic levels throughout the night. Drugs interacting with CYP1A2 are likely to slow-down melatonin metabolism. High variability in bioavailability among subjects calls for dose optimization. Melatonin was essentially safe for short-term use (up to 3 months). Long-term data available for Ped-PRM demonstrate fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%) with no evidence of effects on height, BMI or pubertal development, tolerance or withdrawal effects following long-term use of this product. Studies on long-term safety of IRM and oversight of melatonin supplement manufacture are warranted."

Journal • Autism Spectrum Disorder • CNS Disorders • Fatigue • Genetic Disorders • Insomnia • Pediatrics • Sleep Disorder • CYP1A2

Swedish Internet forum users' views and experiences of melatonin treatments for troubled sleep. (PubMed, Sleep Health) - "The current study suggests that experiences with melatonin treatments are diverse, and the views on exogenous melatonin polarized, albeit with a general consensus on the importance of individual factors when it comes to administration and efficacy. The study also suggests that there is an extensive off-label use of melatonin (eg, younger patients and longer treatment periods than indicated). More studies on melatonin treatments are warranted to bridge the gap between scientific knowledge and clinical practice."

Journal

The Basel BOMP-AID Randomized Trial (clinicaltrials.gov) - P4 | N=190 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2023 ➔ Dec 2024

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders

MeCOVID: Efficacy of Melatonin in the Prophylaxis of Coronavirus Disease 2019 (COVID-19) Among Healthcare Workers. (clinicaltrials.gov) - P2/3; N=450; Completed; Sponsor: Instituto de Investigación Hospital Universitario La Paz; Recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer’s Disease (CTAD 2021) - P2 | "The 2q12 (2:107,510,000–107,540,000) 5–6 SNPs polymorphism cluster may serve as a predictor of cognitive worsening with piromelatine treatment in patients with mild Alzheimer’s disease. In line with previous reports on association between progressive cognitive deterioration with parallel deterioration in sleep (7). The main limitation in the study is the small sample due to the available GWAS specimens."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Insomnia • Psychiatry • Schizophrenia • Sleep Disorder • APOE

Cognitive Behavioral Therapy and Multimodal Therapy in Treating Sleep Disturbance in Patients With Cancer (clinicaltrials.gov) - P2; N=64; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; Trial completion date: Jun 2021 ➔ Jun 2023; Trial primary completion date: Jun 2021 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Sleep Disorder • Solid Tumor

MAST: Effects of Melatonin Supplementation on Renal Physiology in a Habitual Sleep Restricted Population. (clinicaltrials.gov) - P2; N=12; Terminated; Sponsor: Brigham and Women's Hospital; Phase classification: P3 ➔ P2; N=80 ➔ 12; Recruiting ➔ Terminated; International shortage of the chemical para-aminohippuric acid (PAH) due to manufacturing changes, led to inability to perform key measurements to meet trial objectives

Clinical • Enrollment change • Phase classification • Trial termination • Genetic Disorders • Obesity

Chronic Piromelatine Treatment Alleviates Anxiety, Depressive Responses and Abnormal Hypothalamic-Pituitary-Adrenal Axis Activity in Prenatally Stressed Male and Female Rats. (PubMed, Cell Mol Neurobiol) - "Piromelatine also corrected to control level the PNS-induced alterations of corticosteroid receptors only in male offspring. Our findings suggest that the piromelatine treatment exerts beneficial effects on impaired behavioral responses and dysregulated HPA axis in both sexes, while it corrects the PNS-induced changes in the hippocampal corticosteroid receptors only in male offspring."

Journal • Preclinical • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder