Ambulatory blood pressure monitoring (ABPM) is a sensitive method used to determine whether small changes in blood pressure and heart rate are induced by new drugs. This randomized, double-blind, placebo-controlled ABPM trial was used to characterize the blood pressure and heart rate profile of the novel β3-adrenergic receptor agonist vibegron in patients with overactive bladder (OAB).

Patients with OAB were randomly assigned 1:1 to receive once-daily vibegron 75 mg or placebo for 28 days. The primary endpoint was change from baseline to day 28 in mean daytime (waking hours) ambulatory systolic blood pressure. Key secondary endpoints were change from baseline to day 28 in mean daytime ambulatory diastolic blood pressure and heart rate and in mean 24-hour ambulatory systolic blood pressure, diastolic blood pressure, and heart rate. Endpoints were analyzed using linear models and included terms for treatment, age group, sex, pre-existing hypertension, and baseline ABPM values. Point estimates for treatment group means and treatment differences were presented with a 2-sided 90% confidence interval (CI). For the primary endpoint, the upper limit of the CI was evaluated against a criterion of 3.5 mmHg. A sample size of 90 evaluable patients per treatment group would have 75% power to detect a treatment effect of 3.5 mmHg in daytime systolic blood pressure, assuming a standard deviation of 10 mmHg and a 2-sided significance level of 0.10. Given an estimated 10% drop out rate or unevaluable data, planned enrollment was 200 patients.

A total of 214 patients with OAB were randomized; of these, 96 in the vibegron group and 101 in the placebo group had evaluable ABPM measurements at baseline and day 28. Mean age was 59.3 years and 74.6% were female; 39.6% and 30.7% of patients receiving vibegron or placebo, respectively, had pre-existing hypertension. The least squares mean difference (90% CI) change from baseline to day 28 in daytime systolic blood pressure was 0.81 (‒0.88, 2.49) mmHg for vibegron vs placebo (Table). Changes in daytime diastolic blood pressure and heart rate were comparable for vibegron and placebo (Table). The 90% CIs include 0, demonstrating no statistically significant differences were seen in mean 24-hour systolic blood pressure (Figure), diastolic blood pressure, or heart rate (Table). The most commonly reported treatment-emergent adverse event was hypertension (vibegron: n=5 [4.7%, 95% CI=1.6% to 10.7%]; placebo: n=4 [3.7%, 95% CI=1.0% to 9.2%]); no event of hypertension with vibegron was considered treatment related. Of the 5 reported events of hypertension with vibegron, 1 occurred in a patient taking a prohibited medication (phentermine) known to increase blood pressure; this patient was identified as an extreme outlier for ABPM measurements.

In patients with OAB, once-daily vibegron was not associated with clinically meaningful or statistically significant effects on blood pressure or heart rate using ABPM. The upper bound of the 90% CI for change from baseline to day 28 in daytime systolic blood pressure was <2.5 mmHg (lower than the upper limit of 3.5 mmHg) for vibegron vs placebo, providing even stronger evidence that vibegron does not have clinically relevant effects on daytime systolic blood pressure. The safety profile of vibegron was comparable with placebo and consistent with other trials of vibegron in patients with OAB.

Using ABPM, this study shows that the β3-adrenergic receptor agonist vibegron had no clinically or statistically significant effects on blood pressure and heart rate and displayed a hemodynamic safety profile comparable with placebo.