Ospolot (sultiam) / AOP Orphan Pharma - LARVOL DELTA

Loss-of-function variant in KCNH3 is associated with global developmental delay, autistic behavior, insomnia, and nocturnal seizures. (PubMed, Seizure) - "Our results propose KCNH3, which is primarily expressed in the nervous system, as a new disease gene associated with a neurodevelopmental phenotype including seizures."

Journal • Cardiovascular • CNS Disorders • Developmental Disorders • Epilepsy • Insomnia • Mental Retardation • Sleep Disorder • KCNH2 • KCNH3

The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea. (PubMed, ERJ Open Res) - "STM treatment in OSA induced a reduction of both CA activity and HIF-1α concentration. The effects remained 2 weeks after treatment completion, suggesting prolonged effects of STM in OSA."

Biomarker • Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder • HIF1A

Late Breaking Abstract - A randomized, double-blind, placebo controlled, dose-finding trial of sulthiame in obstructive sleep apnea (ERS 2024) - "STM, in the evaluated dose range, provides a consistent reduction of sleep disordered breathing and improvement of sleep quality, hypoxia, and daytime sleepiness. STM is a promising candidate for drug therapy in OSA."

Clinical • Late-breaking abstract • Cardiovascular • Fatigue • Obstructive Sleep Apnea • Pain • Respiratory Diseases • Sleep Disorder

The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnea (ERS 2024) - "STM treatment in OSA induced a reduction of both CA activity and HIF-1α concentration. The effects remained two weeks after treatment completion, suggesting prolonged effects of STM in OSA."

Biomarker • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • HIF1A

SURF: Effect of Sulthiame on EEG in Childhood Epilepsy Syndromes (clinicaltrials.gov) - P=N/A | N=15 | Recruiting | Sponsor: University Hospital, Angers | Trial completion date: Sep 2024 ➔ Nov 2024 | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

The epilepsy phenotype of KCNK4-related neurodevelopmental disease. (PubMed, Seizure) - "Gain-of-function variants in KCNK4 cause a spectrum of epilepsies, ranging from benign isolated epilepsy to epileptic encephalopathy, with focal to bilateral tonic-clonic seizures being the most commonly observed. Importantly, a subgroup of patients present with a mild extra-neurological phenotype without characteristic facial dysmorphism or generalized hypertrichosis. This report expands the phenotypic spectrum of KNCK4-associated disease and provides new insights into the clinical heterogeneity of this rare neurodevelopmental syndrome."

Journal • CNS Disorders • Dermatology • Developmental Disorders • Epilepsy • Mental Retardation • Pain • Psychiatry • KCNK4

Sulthiame use in children with pharmacoresistant epilepsies: A retrospective study. (PubMed, Epileptic Disord) - "These data demonstrate the therapeutic potential of sulthiame, even in patients with highly pharmacoresistant epilepsy. Improvements may be seen in both seizure frequency and sleep SWI."

Journal • Retrospective data • CNS Disorders • Epilepsy • Vascular Neurology • NDUFS1 • SATB1

Retrospective Study Of Sulthiame In Treatment Of Pediatric Epilepsy (CNSF 2024) - "These data indicate that sulthiame is effective and well-tolerated in children with CSWS, regardless of the etiology and type of epilepsy."

Retrospective data • CNS Disorders • Epilepsy

Efficacy, Safety, and Tolerability of Three Doses of Sulthiame in Patients With Obstructive Sleep Apnea. A Randomized, Double-blind, Placebo Controlled, Dose-ranging Study (STM-042/K) (ATS 2024) - P2 | "Treatment with STM in the evaluated dose range provides a consistent reduction of sleep disordered breathing together with improvement of sleep quality, hypoxia, and excessive daytime sleepiness. STM is a promising candidate for drug therapy in moderate to severe OSA. Keywords: RCT; carbonic anhydrase inhibition; drug therapy; obstructive sleep apnea; pharmacology.: 1."

Clinical • Late-breaking abstract • Cardiovascular • Excessive Daytime Sleepiness • Fatigue • Obstructive Sleep Apnea • Pain • Respiratory Diseases • Sleep Disorder

Use of Acetazolamide for Electrical Status Epilepticus During Slow-wave Sleep (AAN 2024) - "Sulthiame has been used to treat ESES successfully but is unavailable in the United States...Eight patients were prescribed AZM as a second-line medication for ESES, first being a benzodiazepine - diazepam or clobazam...The literature is limited on AZM use for ESES. We note that AZM has shown efficacy (66%) comparable to BZDs (60% in other studies), both clinically and electrographically. Since, it is better tolerated we support the consideration of an AZM trial as a second-line medication in patients who have failed or did not tolerate BZDs, prior to initiation of steroids."

CNS Disorders • Epilepsy • Metabolic Disorders • Rare Diseases

Use of Dextrose containing fluids and intralipids in a patient with KCNA1 related neuromyotonia (ACMG 2024) - "Treatment to prevent attacks is limited by lack of clinical trials but commonly used or proposed treatments include Acetazolamide, Phenytoin, Sulthiame, Carbamazepine, and Lamotrigine...She has required antiepileptic medication since presentation of symptoms with most presently being treated with carbamazepine and Ativan... Our patient presents with a familial VUS in KCNA1, which segregates with affected family members with episodic myotonia which is a described phenotype associated with pathogenic variants in KCNA1. Current management includes avoidance of triggers, antiepileptic medication, and acetazolamide which is effective in some patients, but acute management during attacks of myotonia is lacking. In addition to recommended treatment of KCNA1 related disorders which our patient has responded well to for prevention of attacks, our patient and her father have had success in acute treatment of attacks with dextrose containing fluids and intralipids."

Clinical • Ataxia • CNS Disorders • Epilepsy • Gastroenterology • Gynecology • Movement Disorders • Nephrology • Otorhinolaryngology • Renal Calculi • Vertigo

SURF: Effect of Sulthiame on EEG in Childhood Epilepsy Syndromes (clinicaltrials.gov) - P=N/A | N=15 | Recruiting | Sponsor: University Hospital, Angers | Initiation date: Jul 2023 ➔ Oct 2023 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • CNS Disorders • Epilepsy

Pharmacokinetic Variability of Sulthiame: The Impact of Age, Drug-Drug Interactions, and Biochemical Markers of Toxicity in Patients with Epilepsy. (PubMed, Ther Drug Monit) - "This study revealed the extensive intraindividual and interindividual pharmacokinetic variability of sulthiame, with age as a contributing factor. Sulthiame has clinically relevant interactions with clobazam. The use of TDM and pH as a biochemical marker may contribute to individualized and safe sulthiame treatment."

Journal • PK/PD data • CNS Disorders • Epilepsy • CYP2C19

Cannabidiol Effect on the Antiepileptic Drug Serum Levels – Experience from the Danish Epilepsy Center (AES 2023) - "In polytherapy with Cannabidiol with or without clobazam were used: valproic acid (17 case), topiramat (11), perampanel (8), lacosamide (8), rufinamide (8), levetiracetam (7), zonisamid (7), lamotrigine (5), bivaracetam (4), ethosuximide (4), stiripentol (4), eslicarbazepin (2), oxcarbazepine (2), pregabalin (2) and sultiame (1)...Topiramate level in all cases was the same or only slightly increased or decreased... There seems to be no simple relationship between Cannabidiol and most antiepileptic drugs. Cannabidiol politherapy with antiepileptic drugs requires control of serum antiepileptic drug levels especially in polytherapy in such medicine as valproic acid, brivaracetam, lacosamide, and perampanel but also rufinamide."

CNS Disorders • Developmental Disorders • Epilepsy • Movement Disorders

Efficacy, Safety and Tolerability of Sulthiame in Patients With Obstructive Sleep Apnea (OSA) (clinicaltrials.gov) - P2 | N=298 | Completed | Sponsor: Desitin Arzneimittel GmbH | Active, not recruiting ➔ Completed

Trial completion • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Modification of endotypic traits in obstructive sleep apnea by the carbonic anhydrase inhibitor sulthiame. (PubMed, Chest) - "The effect of STM in OSA may be explained by a reduction of ventilatory instability (LG) as well as upper airway collapsibility (V / V)."

Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Modification of OSA endotypic traits by sulthiame (ERS 2023) - "STM reduced AHI in OSA already in the lower concentration range. The effect of STM in OSA may be explained by reduced ventilatory instability and improved upper airway collapsibility.; General respiratory patient care; Physiology; Epidemiology; Cell and molecular biology"

Cardiovascular • Hypertension • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Efficacy, Safety and Tolerability of Sulthiame in Patients With Obstructive Sleep Apnea (OSA) (clinicaltrials.gov) - P2 | N=298 | Active, not recruiting | Sponsor: Desitin Arzneimittel GmbH | Recruiting ➔ Active, not recruiting | Trial completion date: May 2023 ➔ Aug 2023 | Trial primary completion date: Mar 2023 ➔ Aug 2023

Enrollment closed • Trial completion date • Trial primary completion date • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

EPIPOP: Population Pharmacokinetics of Antiepileptic in Pediatrics (clinicaltrials.gov) - P=N/A | N=1000 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Unknown status ➔ Recruiting | Trial completion date: Jun 2022 ➔ Jun 2026 | Trial primary completion date: Jun 2022 ➔ Jun 2026

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

SURF: Effect of Sulthiame on EEG in Childhood Epilepsy Syndromes (clinicaltrials.gov) - P=N/A | N=15 | Not yet recruiting | Sponsor: University Hospital, Angers

New trial • CNS Disorders • Epilepsy

Evaluation of medical treatment and brain magnetic resonance imaging (MRI) in children with electrical status epilepticus in sleep (ESES): A single-center experience (EPNS 2023) - "Levetiracetam, valproic acid, clobazam and sulthiame were used most frequently. These results indicated that MRI findings have no significant correlation with seizure control and reduction of the SWI on the EEG in children with ESES. On the other hand, seizure control correlated significantly with neurocognitive state and seizure frequency and clobazam was found to be very effective in complete seizure control."

Clinical • MRI • CNS Disorders • Epilepsy • Sleep Disorder

Types of focal cortical dysplasias and drug-resistant epilepsy (EPNS 2023) - "A significant reduction in the frequency of attacks was noted when Sultiam was used in girls with typical "fencer's pose" attacks (reduction from 120 to 5 per day)...Among the presented clinical cases for 2022, it was frontal localization in girls (FKD Ia, IIb, IIc). As a result, the best control of attacks was noted with FCD IIb and FCD IIc - Engels IA."

CNS Disorders • Epilepsy

ELECTRICAL STATUS EPILEPTICUS IN SLEEP (ESES): Diagnostic and management challenges: Single centre experience (EPNS 2023) - "Clobazam was used as monotherapy in 4 children, 4 with other antiepileptics (AED) including Lamotrigine, Levetiracetam, Ethosuximide & Sulthiame. 1 child had Sodium Valproate monotherapy, 1 had steroids (non- response to Clobazam)...In our study, Clobazam was found to be superior to other AED monotherapy as reported in the literature. Response to steroids in the LKS cases was 50% with 25% requiring it for 2 years. 92 % of our cases showed significant morbidity of cognition, learning, behaviour, autism and ADHD.Timely neuropsychology assessments and genetic testing was not done for all children."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Psychiatry

Use of sulthiame as add-on therapy in children with non-self-limited focal epilepsies of childhood. (PubMed, Epilepsy Behav) - "In our study, STM was found to be effective and well-tolerated in children and adolescents with non-SeLFE. In the patients who responded, improvement in the EEG was seen."

Journal • CNS Disorders • Epilepsy

ERS International Congress 2022: highlights from the Sleep Disordered Breathing Assembly. (PubMed, ERJ Open Res) - "The currently available options include positive airway pressure and a combination of it and pharmacological agents (e.g. sulthiame). This article summarises the most relevant studies and topics on these subjects presented at the ERS International Congress 2022. Each section has been written by Early Career Members of the ERS Assembly 4."

Journal • Cardiovascular • CNS Disorders • Inflammation • Sleep Disorder