ANTIHYPERTENSIVE EFFECT OF ILOPERIDONE IN PARTICIPANTS WITH BIPOLAR MANIA I WITH COMORBID HYPERTENSION IN A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective: Development of novel antihypertensives and delivery mechanisms to enhance efficacy and compliance is an active area of clinical research. Iloperidone is an alpha1 adrenergic, serotonin and dopamine neurotransmitter receptor antagonist. A post-hoc analysis assessed the antihypertensive effect of iloperidone in a subset of participants in a recent phase 3 bipolar study that had a medical history of hypertension and baseline systolic blood pressure (SBP) readings at or above the hypertension thresholds. Design and method: This phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled male and female participants ages 18-65 years diagnosed with bipolar I disorder. Participants were randomized 1:1 to iloperidone (up to 24 mg/d given twice daily) or placebo for 4 weeks. All patients were hospitalized to ensure compliance with dosing and discontinued other antipsychotic treatment prior to their first dose of study medication. Standing and supine blood pressure and pulse measurements were assessed after the participant had rested in the supine position for at least 3 minutes and again after 2 minutes in the standing position. During the titration (Days 1-7), these measurements were done 3-hours after the morning dosing. Results: Of the 413 participants in the safety population, the subset with baseline SBP > 130 (n = 88 [21.3%]) had notable and statistically significant decreases were seen throughout the 28 days of treatment for participants on iloperidone relative to placebo. This includes differences in SBP (mmHg) reduction from iloperidone (n = 47) to placebo (n = 41) of -8.70 on Day 1 (p = 0.0027), -11.08 on Day 7 (p = 0.0001), and -12.27 on Day 28 (p = 0.0001). For iloperidone treated participants with baseline standing SBP < 130 mmHg (n = 158 [38.3%]), there was less of a decrease in SBP. Conclusions: Iloperidone was able to decrease SBP in participants with baseline Standing SBP > 130 mmHg, including those with comorbid hypertension. Additional studies to assess the blood pressure lowering effects of iloperidone in hypertensive patient populations are warranted.