Post-Authorization Safety Study (PASS) of LysaKare® in Adult Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) Patients

The purpose of the study was to evaluate the effect of arginine/lysine solution administration on serum potassium levels. A systematic assessment of serum potassium levels was performed during infusion and up to 24 hours post start of infusion compared to baseline.

The study schedule for each patient consisted of a screening period followed by an infusion day with an optional overnight in-clinic stay, and a follow up call 48h post infusion.

Screening Phase:

At screening, patient eligibility was determined according to inclusion and exclusion criteria, with evaluation of patient's vital signs, ECG and laboratory parameters. The duration of screening could be as short as one day but could not exceed 7 days. Patients who showed potassium level \> 6.0 mmol/L (\> 5.5 mmol/L for Poland only) at screening could have their potassium level corrected and could be re-screened afterwards.

Treatment Phase:

Eligible patients were admitted to the in-clinic unit and dosed with arginine/lysine solution for infusion of 1,000 mL, which was administered intravenously over a period of 4 hours. Before the infusion (at 0 h time point), a set of baseline tests were performed. During and after the infusion, patient condition was monitored for evaluation of any adverse events. Only patients with a potassium level of ≤ 6 mmol/L at screening (\> 5.5 mmol/L for Poland only) were allowed to be dosed. Potassium testing on the infusion day was performed at 0h (before the infusion), and at 2h, 4h, 6h, 8h, 12h, and 24h after the start of infusion. Vital signs and ECGs were taken as specified in the assessment schedule. All patients were monitored closely for signs and symptoms of hyperkalemia, e.g. dyspnoea, weakness, numbness, chest pain and cardiac manifestations (conduction abnormalities and cardiac arrhythmias). Other common adverse reactions during arginine/lysine solution administration are nausea and vomiting. Before the start of arginine/lysine solution infusion, an intravenous bolus of an anti-emetic was given. The choice of anti-emetic drugs was at the discretion of the physician.

Follow-up Phase:

All patients were called for a safety follow-up in 48 hours after dosing. Patients were not scheduled to receive repeat dosing with arginine/lysine solution as concomitant medication with Lutathera® within 7 days of the arginine/lysine solution infusion in the study.

Eligibility Criteria:
Inclusion Criteria:

* Patients with somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), who are eligible for the treatment with Lutathera as per Lutathera label indication.
* Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related procedures.

Exclusion Criteria:

* Pre-existing hyperkalemia (\>6.0 mmol/L at screening) if not adequately corrected before starting the LysaKare (arginine/lysine) infusion. For Poland only, pre-existing hyperkalemia (\> 5.5 mmol/L at screening) if not adequately corrected before starting the LysaKare (arginine/lysine) infusion.
* Instances when Lutathera is not recommended per the Lutathera Summary of Product Characteristics (SmPC).
* Pregnancy or lactation, positive pregnancy test at screening or pre-dose based on the contraindication for Lutathera.
* Any significant medical or social condition which may interfere with the subject's ability to comply with the study visit schedule or the study assessments.
* Patients who have received any investigational agent within the last 30 days.
* Patients that have received a dose of Lutathera prior to the screening visit or are scheduled for Peptide Receptor Repeat (PRRT) treatment within 7 days of the study infusion of arginine/lysine solution.
* Other protocol-defined exclusion criteria may apply.

Exclusion Criteria (Poland Only):

- Pre-existing hyperkalemia (\> 5.5 mmol/L at screening) if not adequately corrected before starting the arginine/lysine solution infusion.