Summary of safety profile The safety profile of Duvyzat is based on a phase 3, double-blind, placebo-controlled, 18-months study in a total of 179 ambulant DMD patients aged 6 years or older on concomitant steroid treatment, of which 118 receiving givinostat up to 62 mg twice daily and 61 receiving placebo (EPIDYS Study).
9%). Tabulated list of adverse reactions Adverse reactions are listed below according to MedDRA system organ class and frequency (see Table 3). The table contains adverse events reported in givinostat-treated patients at a frequency greater than 2% compared to placebo-treated patients in EPIDYS study.
7 Frequency groupings are defined to the following convention: Very common (≥1/10) and common (≥1/100 to <1/10) uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).
Table 3 – Adverse Drug Reactions reported in givinostat-treated patients at a frequency greater than 2% compared to placebo-treated patients in the placebo-controlled EPIDYS Study System Organ Class Very common Common Infections and infestations Gastroenteritis Blood and lymphatic system disorders Thrombocytopenia(a) Metabolism and nutrition disorders Hypertriglyceridaemia(b) Decreased appetite Psychiatric disorders Anxiety Nervous system disorders Dizziness Vascular disorders Haematoma Gastrointestinal disorders Diarrhoea(c), Vomiting, Abdominal pain(d) Constipation Skin and subcutaneous tissue disorders Erythema, Rash Musculoskeletal and connective tissue disorders Myalgia, Arthralgia, Muscular weakness General disorders and administration site conditions Pyrexia Fatigue Investigations Blood thyroid stimulating hormone increased(e) (a) Thrombocytopenia includes platelet count decreased and thrombocytopenia; (b) Hypertriglyceridaemia includes hypertriglyceridaemia and blood triglycerides increased; (c) Diarrhoea includes diarrhoea and faeces soft; (d) Abdominal pain includes abdominal pain and abdominal pain upper; (e) Blood thyroid stimulating hormone increased includes thyroid function test abnormal and blood thyroid stimulating hormone increased.
Description of selected adverse reactions Haematological changes Givinostat has been shown to reduce platelet count with the greatest reduction observed after approximately 88 days and platelet counts remained low throughout treatment.
There were no serious bleeding events related to thrombocytopenia. After givinostat dose reduction, platelets return to normal values in approximately 3-4 weeks. 2% of patients treated with Duvyzat and in no patient on placebo. 2% as moderate.
Low platelet counts resulted in Givinostat dose reduction in 28% of patients. Patients with baseline platelet counts below the lower limit of normal were excluded from the studies. Decreased haemoglobin and decreased neutrophils were also observed in patients treated with givinostat compared to placebo.
8 Triglyceride changes Givinostat has been shown to increase triglyceride levels, with the greatest increase observed after approximately 221 days. After givinostat dose interruption, triglyceride levels return to baseline values in approximately 90 days.
, levels > 300 mg/dl) resulted in discontinuation and led to dosage modification in 2% and 8%, respectively, of patients treated with Duvyzat. 9% of patients treated with Duvyzat. 7%) as severe. Gastrointestinal disturbances Gastrointestinal disturbances, including diarrhoea, vomiting and abdominal pain occurred in patients treated with givinostat.
Diarrhoea was reported in 38% of patients treated with Duvyzat (with 1 severe case reported) compared to 18% of patients on placebo. Diarrhoea usually occurred within the first few weeks of initiation of treatment with Duvyzat. Vomiting occurred in 29% of patients treated with Duvyzat (with 2 severe cases reported) compared to 13% of patients on placebo.
Vomiting usually occurred within the first 2 months of treatment. Abdominal pain occurred in 34% of patients treated with Duvyzat compared to 23% of patients on placebo. One case of abdominal pain was serious. Description of other laboratory abnormalities Adverse reactions of hypothyroidism and/or thyroid stimulating hormone (TSH) increased occurred in 5% of patients treated with Duvyzat compared to 2% of patients who received placebo.
In addition, hypothyroidism (common) events were observed during long-term treatment. Blood thyroid stimulating hormone levels were generally within 2 times the upper limit of normal with no or minor changes in thyroid hormones. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.