Conclusioni sulla pressione
6.5. Overall Conclusions
The effects of naproxcinod on BP were a central focus of all phases of the naproxcinod
development program. Particular attention was taken to assure standardized, accepted
methodologies to measure BP, including both cuff BP measurements during office visits as well
as extensive use of ABPM studies (3 trials involving 548 participants, with data collected at
various time points up to 13 weeks of treatment) to evaluate BP over an entire 24-hour period
(two dosing cycles).
The results of these studies consistently demonstrated a difference in the BP response to
naproxcinod compared to naproxen. The ABPM studies documented that when comparing
equimolar doses of these two agents, there was a lower (1 to 5 mmHg) BP response with
naproxcinod, and this conclusion was further supported by PK/PD analysis in a subset of
patients. OBPM similarly demonstrated a small but consistent difference in BP between
naproxcinod and naproxen, with the distribution of BP changes in the naproxcinod-treated
patients being similar to that of placebo while naproxen resulted in a shift of this distribution to
higher BP values, with a greater incidence of BP destabilization. Based on these highly
consistent data, naproxcinod mitigates the BP increase seen with naproxen in the overall
population, in particular in these hypertensive OA patients receiving RAB therapy.
Specific attention throughout all phases of the development program was also directed toward
potential hypotensive effects of naproxcinod therapy. No evidence of clinically important side
Naproxcinod NDA 22-478
Advisory Committee Briefing Document
62
effects attributed to hypotension was observed, other than a slightly increased incidence of
dizziness in patients on naproxcinod. There was no evidence of an increased incidence of
discontinuation due to potential hypotension-related adverse effects (see Section 8.7).
