Millions of women worldwide have accidental leakage of urine they cannot control after giving birth. Dealing with this problem can be embarrassing and can even add to feelings of anxiety or depression. If you are experiencing this sort of bothersome accidental bladder leakage, the University of Pennsylvania Health System care team is here to help. A group of doctors and researchers have developed a program, funded by the U.S. National Institutes of Health, to help these new moms. This research study, called Training for Urinary Leakage Improvement after Pregnancy or “TULIP,” is designed to learn more about what treatment options can work best for new moms with bothersome accidental bladder leakage. 

This is a prospective, multinational, randomized, double-blind, clinical trial evaluating the safety and effectiveness of a novel AV interval modulation (AVIM) algorithm downloaded into a previously implanted dual-chamber Medtronic pacemaker. Patients within 90 days of de novo implant of an Astra/Azure pacemaker also having uncontrolled hypertension may be approached for inclusion into this study.

Please refer to Protocol Synopsis (Protocol v1.0 pg 11-12). Please refer to Objectives and Endpoints (Protocol v1.0 pg 22-23). Please refer to Protocol Synopsis (Protocol v1.0 pg 11-12). Please refer to Objectives and Endpoints (Protocol v1.0 pg 22-23). Please refer to Protocol Synopsis (Protocol v1.0 pg 11-12). Please refer to Objectives and Endpoints (Protocol v1.0 pg 22-23). Please refer to Schedule of Assessments (Protocol v1.0 pg 15-17).

Primary Objective: To compare the efficacy of 2 doses of BHV-7000 to placebo as an adjunctive therapy for refractory focal onset epilepsy as measured by the change from baseline in 28-day average seizure frequency. Secondary Objcetives: -To compare the efficacy of 2 doses of BHV-7000 to placebo as adjunctive therapy for refractory focal onset epilepsy as measured by the proportion of subjects that have at least a 50% reduction in seizures per month (28 days). -To compare the efficacy of BHV-7000 to placebo during the first month of treatment. To compare the efficacy of BHV-7000 to placebo during the first week of treatment. -To compare the efficacy of BHV-7000 to placebo on seizure freedom (100% seizure reduction during the DBP). -To compare the efficacy of BHV-7000 to placebo on the patient global impression of change (PGI-C) at week 12. -To assess the safety and tolerability of BHV-7000. Exploratory objectives: -To describe the blood concentrations of BHV-7000 in subjects with refractory focal onset epilepsy -To assess the effect of BHV-7000 on depression in subjects that have symptoms of depression at screening. -To assess the efficacy of BHV-7000 to placebo on the clinician global impression of disease severity. -To compare the efficacy of BHV-7000 to placebo on the patient global impression of change (PGI-C) at week 4. -To assess the efficacy of BHV-7000 to placebo on quality of life (QOL). -To assess the satisfaction of patients treated with BHV-7000 to placebo. Change in log-transformed 28-day adjusted seizure frequency from OP over the 12-week DBP. -Proportion of subjects with at least a 50% reduction in 28-day average seizure frequency over the course of the DBP compared to the OP. -Change in log-transformed 28-day adjusted seizure frequency from OP over the first month of the DBP. -Change in log-transformed 7-day adjusted seizure frequency from OP over the first week of the DBP. -Proportion of subjects that are seizure free during the DBP. - Proportion of subjects at week 12 with PGI-C response of minimally improved, much improved or very much improved. -Safety is assessed by the number of unique subjects with deaths, SAEs, AEs leading to discontinuation, moderate and severe AEs and grade 3 and 4 laboratory abnormalities.

Please refer to Protocol V2.2, Version date 12Feb2024, Section 6.2 (Study Objectives Part B) on page 28 for a full list of primary, secondary, and other exploratory objectives. Please refer to Protocol V2.2, Version date 12Feb2024, Section 7.2 (Study Endpoints Part B) on page 29 for a full list of primary endpoint variables. Please refer to Protocol V2.2, Version date 12Feb2024, Section 7.2 (Study Endpoints Part B) on pages 29 and 30 for a full list of secondary and other exploratory endpoint variables.