4 %). 9 %). Tabulated list of adverse reactions The adverse reactions reported in the active-controlled phase 2 and phase 3 clinical trials in patients exposed to sparsentan in chronic kidney disease population including IgAN and FSGS (N=446) are listed in the table below by MedDRA system organ class and frequency convention: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1 000 to < 1/100); rare (> 1/10 000 to < 1/1000); very rare (< 1/10 000).
Table 1:
Adverse drug reactions observed during clinical trials System organ class Very common Common Uncommon Blood and lymphatic system disorders - Anaemia Metabolism and nutrition disorders Hyperkalaemia - Nervous system disorders Dizziness Headache - Vascular disorders Hypotension Orthostatic hypotension - Renal and urinary disorders Renal impairment Acute kidney injury - General disorders and administration site conditions Oedema peripheral Fatigue - Investigations Blood creatinine increased Elevated transaminasea - a Elevated transaminase includes preferred terms of alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased, and hepatic enzyme increased.
Description of selected adverse reactions Haemoglobin decrease In PROTECT, anaemia or decreased haemoglobin was reported as an ADR in 2 ( 1 %) subjects treated with sparsentan compared to 4 (2 %) irbesartan-treated subjects. Overall, haemoglobin ≤ 9 g/dL was reported at any time post treatment in 7 (3 %) subjects in the sparsentan treatment arm and 4 (2 %) subjects in the irbesartan treatment arm.
This decrease is thought to be in part due to haemodilution. There were no treatment discontinuations due to anaemia. Hepatic associated adverse events In PROTECT, a total of 6 (3 %) subjects in the sparsentan group and 4 (2 %) subjects in the irbesartan group had elevation of liver transaminases exceeding 3 times upper-limit-of-normal without elevation of total bilirubin, after receiving study medication for 168 to 407 days, respectively.
All events were non-serious and asymptomatic, the majority were mild or moderate in intensity, all were reversible, and other reasons have been identified as potential causal factors or as potentially contributing to 10 transaminase elevations.
No clinical symptoms of hepatic injury were observed. In the sparsentan group, the study drug was discontinued in 3 subjects after positive rechallenge while in 2 subjects sparsentan treatment, was restarted with no repeated hepatic enzyme elevations.
Acute kidney injury (AKI) In PROTECT, acute kidney injury ADRs were reported in 4 (2 %) subjects in the sparsentan group and 3 (1 %) subjects in the irbesartan group. Four subjects (2 %) who received sparsentan reported serious AKI all of which were reversible.
None of the serious AKI required dialysis. In the sparsentan group, the study drug was discontinued in 3 subjects. Hyperkalaemia In PROTECT, hyperkalaemia was reported as an ADR in 20 (10 %) subjects treated with sparsentan compared to 16 (8 %) irbesartan-treated subjects.
All events were non-serious in subjects treated with sparsentan, the majority were mild to moderate in intensity and all were reversible. There were no treatment discontinuations due to hyperkalaemia. The risk of hyperkalaemia is increasing for patients with a lower eGFR.
Hypotension Hypotension was reported during treatment with sparsentan. In PROTECT, a SBP <= 100 mmHg or a reduction in SBP exceeding 30 mmHg, was reported in 12 % and 10 % of patients on sparsentan, respectively, versus 11 % and 10 % on irbesartan.
4 %) were ≥ 65 years old. Hypotension was reported in 20 (11 %) subjects < 65 years of age and in 6 (40 %) subjects 65 to 74 years of age. 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.