Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness and Other Non-Muscular Symptoms in Patients With Myotonic Dystrophy Type 1

Completed · Phase 2 · Has a placebo group

Conditions studied: Myotonic Dystrophy 1, Excessive Daytime Sleepiness

In brief

The primary objective of this study is to evaluate the safety and efficacy of pitolisant compared with placebo in treating excessive daytime sleepiness (EDS) in patients with Myotonic Dystrophy Type 1 ages 18 to 65 years. The secondary objectives of this study are to assess the impact of pitolisant on fatigue, cognitive function and the burden of disease along with assessing the long-term safety and effectiveness of pitolisant in patients with Myotonic Dystrophy Type 1 ages 18 to 65 years.

Key facts

Study ID: NCT04886518
Run by: Harmony Biosciences Management, Inc.
People needed: 30
Starts: 2021-06-28
Expected to finish: 2024-10-31
Last updated by the study team: 2025-04-25

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Is able to provide voluntary, written informed consent.
Has a diagnosis of DM1 confirmed by genetic testing (cytosine-thymine-guanine [CTG] repeat of ≥100) from the Screening Visit.
Male or female patients ages 18 to 65 years at the time of enrollment.
Has a Clinical Global Impression of Severity (CGI-S) assessment of moderate or severe for overall severity of EDS at Screening.
If on a wake-promoting treatment that could affect EDS (including stimulants, modafinil, and armodafinil):
Must be on a stable dose for at least 2 months prior to Screening and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase).
If not on a stable dose for 2 months prior to Screening, washout for 5 half-lives prior to randomization and agree to remain off these treatments for the duration of the Double-Blind Treatment Phase of the study.
Washout of cannabidiol and tetrahydrocannabinol for 28 days prior to randomization and agree to remain off for the duration of the Double-Blind Treatment Phase of the study.
Able to walk independently with or without an assistive device (e.g., cane, walker, orthoses allowed).
A patient who is a female of child-bearing potential (FCBP) must have a negative serum pregnancy test at the Screening Visit and negative urine pregnancy test at the Baseline Visit and agree to remain abstinent or use an effective method of non-hormonal contraception to prevent pregnancy for the duration of the study and for 21 days after final dose of study drug.
In the opinion of the Investigator, the patient is capable of understanding and complying with the protocol and administration of oral study drug.

You may not qualify if…

Has a diagnosis of another genetic or chromosomal disorder that is distinct from DM1 and that is not being managed adequately in the opinion of the Investigator.
Experiences <6 hours on average of sleep per night based on their sleep diary during Screening (patients need to record at least 7 of 10 consecutive nights including 2 nights that fall on a weekend in their sleep diary during Screening).
Consistently consumes >600 mg of caffeine per day and is unable/unwilling to reduce caffeine intake to <600 mg per day for the duration of the Double-Blind Treatment Phase of the study; caffeine intake should remain consistent during Screening and throughout the Double-Blind Treatment Phase of the study.
Does not agree to discontinue any prohibited medication or substances listed in the protocol.
Is currently breastfeeding or planning to breastfeed over the course of the study. Lactating women must agree not to breastfeed for the duration of the study (Double-Blind Treatment Phase and OLE Phase) and for 21 days after final dose of study drug.
Participation in an interventional research study involving another investigational medication or device in the 28 days prior to enrollment; patients who undergo a washout of an investigational medication of at least 5 half-lives can be enrolled in the Double-Blind Treatment Phase of the study. Patients considering participation in another interventional research study in the OLE Phase must consult with the Investigator who will consult with the Medical Monitor.
Has a primary diagnosis of severe psychiatric illness.
Patients taking antidepressants who have not been on a stable dose of their antidepressant for at least 12 weeks prior to Screening; for patients on a stable dose of their antidepressant for at least 12 weeks prior to Screening, must agree to continue their stable dose for the duration of the Double-Blind Treatment Phase of the study. Dose adjustments will be permitted in the OLE Phase. In the Double-Blind Treatment Phase of the study, antidepressants that are strong CYP2D6 inhibitors are exclusionary.
Has a history of sleep-disordered breathing or another underlying sleep disorder that in the opinion of the Investigator is a main contributory factor to the patient's EDS.
Has a diagnosis of end-stage renal disease (ESRD; estimated glomerular filtration rate [eGFR] of <15 mL/minute/1.73 m2) or severe hepatic impairment (Child-Pugh C).
Has a diagnosis of moderate or severe renal impairment (eGFR ≥15 to ≤59 mL/minute/1.73 m2) or moderate hepatic impairment (Child-Pugh B) at Screening or during the Double-Blind Treatment Phase.
Has a family history of sudden cardiac death, unexplained death, or death from a primary dysrhythmia potentially associated with QT prolongation in any family member (i.e., first degree relative such as parent, sibling, or offspring).
Has a history of unexplained syncope.
Has a history of long corrected QT interval (QTc) syndrome or corrected QT interval using Fridericia's formula (QTcF) >450 msec for males or >470 msec for females (QTcF = QT / 3√ RR) sustained atrial fibrillation (AF) or left ventricular ejection fraction <50%.
Has a history of documented symptomatic arrhythmias (e.g., ECG, Holter monitor).
Electrocardiogram abnormalities during a 10-second, 12-lead ECG at Screening of first degree atrioventricular block (AVB; PR interval >220 msec), QRS >120 msec, heart rate (HR) <50 beats per minute (bpm), marked T-wave abnormalities, more than single atrial premature complexes (APCs) or premature ventricular contractions (PVCs), left bundle branch block, or Brugada pattern type 1.
Note: Patients with 1st degree AVB with a PR interval >220 msec, who are treated prophylactically with an allowable implanted device are not excluded from the study.
Based on Holter monitor, any episode of 3rd degree AVB, any prolonged episode of second degree AVB (>2 episodes during waking hours, >6 episodes during sleep), any prolonged episode of 2nd degree AVB (>10 seconds), any asystole longer than 3.5 seconds, any run of ventricular tachycardia (VT) >6 beats, frequent runs of non-sustained VT (>5/24 hour), >400 PVCs/24 hours, AF or paroxysmal AF, or frequent or complex atrial arrhythmias.
Has history of New York Heart Association (NYHA) class III or class IV heart failure.
Has an implanted defibrillator or implanted biventricular pacemaker. Note: Patients with implanted univentricular pacemakers that are used prophylactically to prevent or treat bradycardia or heart block may be included.
Is receiving a medication known to prolong the QT interval.
Has a history of clinically significant hypokalemia or hypomagnesemia that cannot be adequately controlled by supplementation.
Has serum potassium or magnesium levels that are outside of the normal reference ranges and considered clinically significant at Screening. Patients with mild hyperkalemia that, in the opinion of the Investigator, does not pose an arrhythmia threat may be included.
Is receiving a concomitant medication that is known to be a strong cytochrome P450 (CYP) 2D6 inhibitor, a strong CYP3A4 inducer; or a centrally acting histamine 1 receptor (H1R) antagonist (sedating antihistamine).
Note: Patients who undergo a washout of these medications of at least 5 half-lives may be enrolled in the Double-Blind Treatment Phase of the study.

Where it is running

UCI Center for Clinical Research — Irvine, California, United States
University of Colorado School of Medicine — Aurora, Colorado, United States
University of South Florida — Tampa, Florida, United States
Rare Disease Research — Atlanta, Georgia, United States
Indiana University — Indianapolis, Indiana, United States
Kennedy Krieger Institute Center for Genetic Muscle Disorders — Baltimore, Maryland, United States
University of Minnesota — Minneapolis, Minnesota, United States
University of Rochester Medical Center — Rochester, New York, United States
University of North Carolina — Chapel Hill, North Carolina, United States
Wake Forest — Winston-Salem, North Carolina, United States
University of Pennsylvania — Philadelphia, Pennsylvania, United States
The Ottawa Hospital — Ottawa, Ontario, Canada
Hôpital de Chicoutimi — Chicoutimi, Quebec, Canada

Full record on ClinicalTrials.gov

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