Title
Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1
Double-Blind, Placebo-Controlled, Dose-Range-Finding, Crossover Trial of Single Day Administration of ERX-963 in Adults With Myotonic Dystrophy Type 1
Phase
Phase 1Lead Sponsor
Expansion Therapeutics, Inc.Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Myotonic Dystrophy, Type 1 (DM1) Myotonic DystrophyIntervention/Treatment
ERX-963 ...Study Participants
12Participants in this study will receive two treatments, placebo and ERX-963, on different days in a randomized fashion.
The primary purpose of this study is to investigate the safety and tolerability of ERX-963 in participants diagnosed with Myotonic Dystrophy, Type 1 (DM1).
The secondary purpose is to evaluate the potential of ERX-963 treatment to reduce excessive daytime sleepiness / hypersomnia and improve cognitive function in DM1 participants compared to placebo treatment.
This study is evaluating single administration of two dose levels of ERX-963 to explore the relationship between dose, safety, tolerability, exposure and clinical benefit. This is a multi-center, randomized, double-blind, placebo-controlled, two-treatment period crossover study in two cohorts of participants with DM1.
Participants who have consented and meet eligibility criteria will receive two treatments, placebo and ERX-963, in a randomized crossover fashion with a washout period between the treatments. On treatment days, participants will receive treatment followed by repeated blood collection for pharmacokinetic analysis and administration of a battery of outcome measures relevant to sleep and cognition.
Active medicine
Comparator
Participants in this arm will receive ERX-963 followed by a washout period. After the washout period, participants will receive placebo.
Participants in this arm will receive placebo followed by a washout period. After the washout period, participants will receive ERX-963.
Key Inclusion Criteria: 18 to 65 years of age DM1 defined by genetic testing or clinical-confirmation Epworth Sleepiness Scale (ESS) of > 11 or participants who have long sleep periods of an average of > 10 hours a day Age of onset of DM1 greater than 16 years Key Exclusion Criteria: Significant respiratory compromise Significant cardiac disease Diagnosis of symptomatic Restless Leg Syndrome or significant untreated nocturnal hypoxias Significant moderate to severe hepatic insufficiency Clinically active depression, anxiety, or other medical condition that, in the investigator's opinion, would interfere with the safety and efficacy assessments History of seizures History of panic disorders
| Event Type | Organ System | Event Term | Cohort 1: Placebo Period | Cohort 1: 1 mg ERX-963 Period | Cohort 2: Placebo Period | Cohort 2: 2 mg ERX-963 Period |
|---|
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. Treatment-emergent AEs were AEs which started between the date and time of study drug dosing and through Study Day 2, within each period. Drug-related AEs were assessed by the investigator to determine the relationship (related or unrelated) between the study intervention and each AE occurrence.
Participants will self-report their level of sleepiness by self-rated questionnaire "Stanford Sleepiness Scale" (SSS). This is a single item questionnaire on a 7-point scale (1-7). Higher values indicate worse outcome.
The PGI-I is a 7-point rating system used by the patient to rate their overall clinical condition after intervention relative to before intervention where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse, and 7=very much worse.
The CGI-I is a 7-point rating system used by the clinician or investigator to compare the patient's overall clinical condition after intervention relative to before intervention where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse, and 7=very much worse (Guy, 1976; Busner, 2007).
Participants will be tested for their response time and number of lapses during the PVT.
Participants will be tested for the proportion of correct response to the One-back task.
