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

Inclusion Criteria

• Ambulant patients with BMD diagnosis confirmed by genetic testing.
• Able and willing to give informed consent in writing.
• Able to perform 6MWT at screening with a minimum distance of 200 m and maximum distance of 450 m.
• If in treatment with systemic corticosteroids and/or angiotensin-converting-enzyme (ACE) inhibitor , and/or β or α adrenergic receptor blocker, no significant change in dosage or dosing regimen (excluding changes related to body weight) was to be presented for a minimum of 6 months prior to start of study treatment.
• Patients had to be willing to use adequate contraception from randomization until 3 months after the last dose of study treatment, and included the following:
• True abstinence when in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar ovulation, symptothermal, post ovulation methods) and withdrawal were not acceptable methods of contraception.
• Condom with spermicide, with the female partner using an acceptable method of contraception, such as an oral, transdermal, injectable or implanted steroid-based contraceptive, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such as a cervical cap with spermicide jelly.

Exclusion Criteria

• Exposure to another investigational drug within 3 months prior to the start of study treatment.
• 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.
• Surgery that could have affected muscle strength or function within 3 months before study entry or planned surgery at any time during the study.
• 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.
• 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.
• Platelet count, white blood cell (WBC) count and hemoglobin at screening less than the lower limit of normal (LLN). If laboratory screening results were . 1.5 x upper limit of normal [ULN]), unless secondary to Gilbert's disease or pattern consistent with Gilbert's disease.
• 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.
• Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening.
• 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).
• 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.
• Hypersensitivity to the components of the study medication.
• Sorbitol intolerance or sorbitol malabsorption, or the hereditary form of fructose intolerance.
• Contraindications for muscle biopsy.
• Contraindications forMRI/MRS (e.g., claustrophobia, metal implants or seizure disorders).
• 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.