Comparison of the efficacy, tolerability, and smoothness indexes of two nifedipine formulations: a randomized, double-dummy, double-blind, controlled trial

Abstract

Background: Nifedipine is an effective dihydropyridine calcium channel antagonist used in the treatment of high blood pressure (BP), although side effects related to its potency and short half-life have led to development of a sustained-release formulation, nifedipine gastrointestinal therapeutic system (N-GITS) with osmotic pump. Objective: This study compared the efficacy, tolerability, and smoothness indexes of 2 formulations of nifedipine—N-GITS and slow-release microgranules (N-MG)—in patients with hypertension. Methods: This was a randomized, double-dummy, double-blind, controlled trial in outpatients with mild to moderate essential hypertension (sitting diastolic BP [DBP] >90 and <115 mm Hg). Patients were randomized to receive either N-GITS 30 mg plus N-MG placebo or N-MG 30 mg plus N-GITS placebo once daily for 12 weeks. In patients who had not achieved adequate BP control (DBP <90 mm Hg or a decrease in DBP of >10 mm Hg compared with baseline) at week 3, the dose of the respective formulations was increased to 60 mg once daily for the remainder of the trial. The primary end point was change in mean BP over 24 hours. In addition, the smoothness indexes of both formulations were compared between groups to evaluate the homogeneity of their antihypertensive effects. Tolerability was assessed in terms of the incidence of adverse events. Results: Fifty-four outpatients (44 women, 10 men; mean age, 54 years) were enrolled, 26 in the N-GITS-treated group and 28 in the N-MG-treated group. A decrease in mean BP over 24 hours was observed in both groups, with no significant differences between groups. The N-GITS-treated group showed a slight but statistically significant increase in heart rate (HR) at 12 weeks ( P = 0.017); the N-MG-treated group showed a slight but statistically significant decrease in HR ( P = 0.03). Smoothness index values (mean ± SD) for active drug versus comparison-drug placebo in all patients (including nonresponders) were 0.466 ± 0.5 for the N-GITS—treated group and 0.459 ± 0.4 for the N-MG—treated group. The corresponding smoothness index values when nonresponders (N-GITS, 1 nonresponder, 25 responders; N-MG, 3 nonresponders, 25 responders) were excluded were 0.716 ± 0.5 and 0.707 ± 0.7, respectively. No statistically significant difference in smoothness index was found between the 2 groups. Conclusion: The results of this study suggest that N-GITS and N-MG have similar therapeutic effects and smoothness indexes.