Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Becker Muscular Dystrophy

Exclusion Criteria

• •1. Exposure to another investigational drug within 3 months prior to the start of study treatment.
• •2. Use of any pharmacological treatment, other than corticosteroids, that could have affected muscle strength or function within 3 months prior to the start of study treatment (e.g., growth hormone). vitamin D, calcium, and other supplements were allowed.
• •3. Surgery that could have affected muscle strength or function within 3 months before study entry or planned surgery at any time during the study.
• •4. Presence of other clinically significant disease that in the Investigator's opinion could have adversely affected the safety of the patient or could have impaired the assessment of study results.
• •5. A diagnosis of other uncontrolled neurological diseases or presence of relevant somatic disorders not related to BMD that could have interfered with the ability to perform the muscle function tests and/or to comply with the study protocol procedures.
• •6. Platelet count, white blood cell (WBC) count and hemoglobin at screening less than the lower limit of normal (LLN). If laboratory screening results were \< LLN, platelet count, WBC count and hemoglobin were to be repeated once, and if again \< LLN became exclusionary.
• •7. Symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction \< 50% at screening or with heart transplant.
• •8. Current liver disease or impairment, including but not limited to elevated total bilirubin (\>. 1.5 x upper limit of normal \[ULN\]), unless secondary to Gilbert's disease or pattern consistent with Gilbert's disease.
• •9. Inadequate renal function defined by serum cystatin C \> 2 x ULN. If the value was \> 2 x ULN, serum Cystatin C was to be repeated once, and if again \> 2 x ULN became exclusionary.
• •10. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening.
• •11. Baseline corrected QT interval using Fridericia's correction (QTcF) \> 450 msec (as the mean of 3 consecutive readings 5 minutes apart) or history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, or family history of long QT syndrome).
• •12. Current psychiatric illness/social situations rendering the patient unable to understand or comply with the muscle function tests and/or with the study protocol procedures.
• •13. Hypersensitivity to the components of the study medication.
• •14. Sorbitol intolerance or sorbitol malabsorption, or the hereditary form of fructose intolerance.
• •15. Contraindications for muscle biopsy.
• •16. Contraindications forMRI/MRS (e.g., claustrophobia, metal implants or seizure disorders).
• •17. Hypertriglyceridemia (˃ 1.5 x ULN). At screening, patients with hypertriglyceridemia could be enrolled if on stable treatment and with controlled levels of triglycerides (i.e., within normal range) for at least six months.