Randomized, multicenter, active-controlled open-label study of NPC-25, zinc histidine hydrate, (non-inferiority to NOBELZIN™, zinc acetate dihydrate) for patients with hypozincemia

Objective

This study evaluated the efficacy and safety of NPC-25, zinc histidine hydrate, in patients with hypozincemia. This randomized multicenter active-controlled open-label trial aimed to verify the non-inferiority of NPC-25 to NOBELZIN™, zinc acetate dihydrate.

Methods

Participants whose serum zinc concentrations were <70 μg/dL at two points within 8 weeks before the start of treatment were randomized 1:1 into the NPC-25 (active drug) administration group and the NOBELZIN™ (control drug) administration group, using dynamic allocation. The initial daily doses were 50 mg or 100 mg as the baseline serum zinc levels, and administration periods were set at maximum of 24 weeks with the goal of maintaining the target serum zinc concentration (≥80 and <200 μg/dL) for 8 weeks, with extension up to 52 weeks as needed in the NPC-25 group, but not the NOBELZIN group. The primary efficacy endpoint was the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dosage within 24 weeks after the start of administration. The key secondary endpoints were the cumulative achievement percentage for target serum zinc concentration at each observation time point, the cumulative achievement percentage for maintenance of target concentration for 8 weeks at the same dosage at each observation time point, change in mean serum zinc concentration, and comparison of dosage amount. Safety assessments included the incidence of adverse events and adverse drug reactions, as well as changes in clinical laboratory and physical measurements.

Results

For the primary endpoint for full analysis (FAS) set (n=103, NPC-25 group; n=107, NOBELZIN group), the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dose was 86.4 % (89/103) in the NPC-25 group and 80.4 % (86/107) in the NOBELZIN group, which confirmed the non-inferiority of NPC-25 to NOBELZIN™. For the secondary endpoint for FAS, at each observation point, although there was no significant difference between the two groups in the proportion of participants who achieved the target serum zinc concentration, there was a tendency that the maintenance of the target concentration for 8 weeks was achieved earlier with NPC-25.

There was also a tendency to achieve maintenance with a lower daily dose in the NPC-25 group. Furthermore, at each observation point, there was no significant difference between the two groups in terms of the mean serum zinc concentration or the average change in serum zinc concentration from baseline. In the safety assessment for safety population (SP), the incidence of nausea and vomiting was lower with NPC-25 than with NOBELZIN (2.8 % and 6.4 % with nausea, 0.9 % and 2.8 % with vomiting), but there were no significant differences in other adverse drug reactions.

Conclusion

In this study, non-inferiority of NPC-25 to NOBELZIN™ was confirmed in terms of efficacy and safety. Furthermore, regarding safety, NPC-25 resulted in a lower frequency of digestive symptoms, such as nausea and vomiting.