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

NCT04886518 | Completed Phase 2 Results FDA Drug

• 1 other identifier: HBS-101-CL-005
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 13

Brief Summary

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.

Conditions

Myotonic Dystrophy 1; Excessive Daytime Sleepiness

Outcome Measures

Primary Outcomes (1)

• Change in Excessive Daytime Sleepiness (EDS) Based on Change in Daytime Sleepiness Scale (DSS) Score

  The score of the DSS ranges from 0 to 15. A decrease in the DSS score represents an improvement in EDS.

  Baseline to Week 11

Secondary Outcomes (9)

• Change in Fatigue Based on Change in Fatigue Severity Scale (FSS) Score

  Baseline to Week 11

• Change in Psychomotor Function Based on Change in Cogstate Detection Test

  Baseline to Week 11

• Change in Attention Based on Change in Cogstate Identification Test

  Baseline to Week 11

• Change in Working Memory Based on Change in Cogstate One Back Test

  Baseline to Week 11

• Change in Burden of Disease Based on Change in Myotonic Dystrophy Health Index (MDHI)

  Baseline to Week 11

Study Arms (3)

Higher dose pitolisant

ACTIVE COMPARATOR

Double-Blind Treatment Phase: Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 35.6 mg pitolisant administered once daily in the morning.

Drug: Pitolisant Oral Tablet

Lower dose pitolisant

ACTIVE COMPARATOR

Double-Blind Treatment Phase: Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning

Drug: Pitolisant Oral Tablet

Placebo

PLACEBO COMPARATOR

Double-Blind Treatment Phase: Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets

Drug: Placebo oral tablet

Interventions

Pitolisant Oral Tablet DRUG

Pitolisant 4.45 mg tablets: white, round, plain, biconvex film-coated tablet, 3.7 mm in diameter. Each tablet contains 5 mg of pitolisant hydrochloride equivalent to 4.45 mg of pitolisant. Pitolisant 17.8 mg tablets: white, round, plain, biconvex film-coated tablet, 7.5 mm in diameter. Each tablet contains 20 mg of pitolisant hydrochloride equivalent to 17.8 mg of pitolisant.

Higher dose pitolisant; Lower dose pitolisant

Placebo oral tablet DRUG

Matching placebo tablets will be provided for each strength of active pitolisant film-coated tablets.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• 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.

Sponsors & Collaborators

• Harmony Biosciences Management, Inc.: lead

Study Sites (13)

UCI Center for Clinical Research

Irvine, California, 92697, United States

Location

University of Colorado School of Medicine

Aurora, Colorado, 80045, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Rare Disease Research

Atlanta, Georgia, 30329, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Kennedy Krieger Institute Center for Genetic Muscle Disorders

Baltimore, Maryland, 21205, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27157, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The Ottawa Hospital

Ottawa, Ontario, Canada

Location

Hôpital de Chicoutimi

Chicoutimi, Quebec, Canada

Location

Related Publications (1)

• D'Ambrosio ES, Chuang K, David WS, Amato AA, Gonzalez-Perez P. Frequency and type of cancers in myotonic dystrophy: A retrospective cross-sectional study. Muscle Nerve. 2023 Aug;68(2):142-148. doi: 10.1002/mus.27801. Epub 2023 Mar 27.

  PMID: 36790141 DERIVED

MeSH Terms

Conditions

Myotonic Dystrophy; Disorders of Excessive Somnolence

Interventions

pitolisant

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Mental Disorders

Results Point of Contact

• Title: Sharon Wolfe-Schwartz, Executive Director, Medical and Regulatory Writing
• Organization: Harmony Biosciences

swolfe-schwartz@harmonybiosciences.com

267-965-0270

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 14, 2021
• Study Start: June 28, 2021
• Primary Completion: October 6, 2023
• Study Completion: October 31, 2024
• Last Updated: April 25, 2025
• Results First Posted: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (11)