Overview

This study is testing a medicine called surlorian in adults who have a genetic muscle condition known as autosomal dominant RYR1-related myopathy (RYR1-RM). The goal is to find out whether surlorian improves muscle weakness, and whether it is safe and well tolerated.

Eligibility

Inclusion Criteria:

• Can understand the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with all protocol requirements
• Confirmed genetic diagnosis of RYR1-RM with autosomal dominant mutation
• Clinical evidence of weakness affecting any proximal muscle group(s) as assessed by the Investigator
• Can walk 10 m with or without a cane (no other walking aid allowed)
• Is either a female of non-childbearing potential or male or female, who agrees to use highly effective contraception/preventive exposure measures from the time of first dose of IP (for a male participant) or the signing of the informed consent form (ICF) (for a female participant) during the trial, and until 7 days after the last dose of IP.

Exclusion Criteria:

• Unable or unwilling to understand and comply with protocol requirements or unlikely to complete the study as planned, as judged by the Investigator
• Any clinically significant medical condition that, in the opinion of the Investigator, would interfere with the study
• Females who are pregnant, breastfeeding or intend to become pregnant, or of childbearing potential not using adequate contraceptive methods
• Participants with severe pulmonary dysfunction at screening, or evidence of pulmonary exacerbation (defined as an acute worsening of respiratory symptoms that result from a decline in lung function)
• Cardiac disease by history or at screening that, in the Investigator's opinion, is likely to worsen overall performance of efficacy measures during the study
• History of seizure disorder, neurologic disease, or neuromuscular disease other than RYR1-RM
• History of chronic orthopedic issues, acute injury, or expected surgery during the study that may affect the ability to complete study assessments
• Positive test results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
• Participants with screening alanine aminotransferase (ALT) levels \>3 × upper limit of normal (ULN) or screening aspartate aminotransferase (AST) levels \>5 × ULN (isolated elevations of total bilirubin \<2 × ULN with direct bilirubin below the ULN will be included)
• History within the past year of alcohol or other drug substance abuse
• Known hypersensitivity to the investigational product of related compounds
• Treatment with statins, proton pump inhibitors or H2 blockers within 7 days or 5 half-lives, whichever is longer, prior to the first dose of the study drug
• Treatment with sensitive or narrow therapeutic index CYP3A4 substrates within 7 days or 5 half-lives, whichever is longer, prior to first dose of the study drug
• Treatment with strong or moderate CYP2C8 inhibitor or inducers within 7 days or 5 half-lives, whichever is longer, prior to the first dose of the study drug
• Currently enrolled in another study or received treatment with any other investigational drug within 30 days or \> 5 half-lives, whichever is longer, prior to screening
• Has reported any suicide ideation of Category 4 or 5 on the C-SSRS within 6 months prior to screening or any suicidal behavior in the last two years prior to screening as indicated by any 'yes' answers on the suicidal behavior section of the C-SSRS