E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult men and women with either:
* OAB Wet
* OAB Dry |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 100000004857 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Safety Objective: To evaluate the safety and tolerability of vibegron for up to 52 weeks in patients with symptoms of overactive bladder (OAB) who previously completed treatment in study RVT-901-3003 |
|
E.2.2 | Secondary objectives of the trial |
Secondary and Exploratory Efficacy Objectives:
* To evaluate the efficacy of vibegron in patients with symptoms of OAB
* To evaluate the effect of vibegron on patient-perceived outcomes in patients with symptoms of OAB
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Has completed participation in study RVT-901-3003.
2. Willing and able to provide written informed consent.
3. For females of reproductive potential: Agrees to remain abstinent or use (or have their male partner use) an acceptable method of birth control (as defined in Section 5.2.1) each time the patient has intercourse until the Follow-up Visit.
4. For females of reproductive potential: Agrees not to donate ova (eggs) until at least 1 month after the last dose of Study Treatment.
5. Has demonstrated ≥ 80% compliance with self-administration of Study Treatment in study RVT-901-3003.
6. Has completed a minimum of 4 Complete Diary Days for study RVT-901-3003 Week 12.
7. Is ambulatory and in good general physical and mental health as determined by the Investigator.
8. In the opinion of the Investigator, is able and willing to comply with the requirements of the protocol, including completing electronic versions of questionnaires, the Voiding Diary, and Voided Volume Diary (will require ability to collect, measure, and record voided volume by herself/himself using a graduated urine collection and measurement container [provided by the Sponsor, if needed]).
|
|
E.4 | Principal exclusion criteria |
1. Was unable to complete participation in study RVT-901-3003 for any reason.
2. Has a change in history or current evidence of any clinically significant condition, therapy, lab abnormality, or other circumstance that might, in the opinion of the Investigator, confound the results of the study, interfere with the patient’s ability to comply with study procedures, or make participation in the study not in the patient’s best interest. Includes any serious or unstable, clinically relevant change in gastrointestinal, renal, hepatic, cardiovascular, lymphatic, or psychiatric, or other medical disorder during the RVT-901-3003 study
3. Has coronary or neurovascular interventions planned during the duration of the study.
4. Has uncontrolled hyperglycemia (defined as fasting blood glucose >150 mg/dL or 8.33 mmol/L and/or non-fasting blood glucose >200 mg/dL or 11.1 mmol/L) based on most recent available lab results in study RVT-901-3003 or, if in the opinion of the Investigator, is uncontrolled.
5. Has uncontrolled hypertension (systolic blood pressure of ≥ 180 mm Hg and/or diastolic blood pressure of ≥ 100 mm Hg) or has a resting heart rate (by pulse) > 100 beats per minute.
a. Patients who have systolic blood pressures ≥ 160 mm Hg or < 180 mm Hg are excluded, unless deemed by the Investigator and/or Medical Monitor as safe to proceed in this study and able to complete the study per protocol; these patients must be on stable hypertension medication for at least 90 days.
b. All patients with signs and symptoms of uncontrolled hypertension, regardless of blood pressure measurement, are excluded from the study. These include, but are not limited to neurological symptoms or findings, hematuria, proteinuria, retinopathy, unstable angina, acute heart failure.
6. Has clinically significant ECG abnormality which, in the opinion of the Investigator, exposes the patient to risk by participating in the study
7. Has alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit of normal (ULN), or bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome) based on most recent available lab results in study RVT-901-3003.
8. Has an estimated glomerular filtration rate (eGFR) < 30mL/min/1.73 m2 based on most recent available lab results in study RVT-901-3003.
9. Use of any prohibited medications as detailed in Section 7.7.3.
10. Plans to initiate or change the dosing of any medications listed in Section 7.7.5 during the study that in the opinion of the investigator is assessed to be clinical significant.
11. Has an allergy, intolerance, or a history of a significant clinical or laboratory adverse experience associated with any of the active or inactive components of the vibegron formulation or tolterodine formulation.
12. Is currently participating or has participated in a study with an investigational compound or device within 28 days of signing informed consent, not including participation in study RVT-901-3003.
13. Has a history of significant drug or alcohol abuse/dependence within a year of informed consent, as assessed by the investigator.
14. Has a varying sleep schedule anticipated during times when the voiding diaries are to be completed.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Safety Endpoint: Incidence of any adverse event by system organ class and preferred term |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary Endpoints:
* Change from baseline (CFB) at Week 52 in average number of micturitions per 24 hours in all OAB patients
* CFB at Week 52 in average number of urge urinary incontinence (UUI) episodes per 24 hours in OAB Wet patients
* CFB at Week 52 in average number of urgency episodes (need to urinate immediately) over 24 hours in all OAB patients
* Percent of all OAB patients with a 50% reduction from baseline in urgency episodes (need to urinate immediately) per 24 hours at Week 52
* Percent of OAB Wet patients with a 75% reduction from baseline in UUI episodes per 24 hours at Week 52
* CFB at Week 52 in average number of total urinary incontinence episodes over 24 hours in OAB Wet patients
* CFB at Week 52 in average volume voided per micturition in all OAB patients
* CFB at Week 52 in Coping Score from the OAB-q LF (1 week recall) in all OAB patients
* CFB at Week 52 in Health-related Quality of Life (HRQL) Total Score from the OAB-q LF (1-week recall) in all OAB patients
* CFB at Week 52 in Symptom Bother Score from the OAB-q-LF (1-week recall) in all OAB patients
Exploratory Endpoints:
* Percent of OAB Wet patients with zero UUI episodes at Week 52
* Percent of all OAB patients with average number of micturitions < 8 per 24 hours at Week 52
* Percent of OAB Wet patients with a 50% reduction from baseline in total incontinence episodes per 24 hours at Week 52
* Percent of OAB Wet patients with zero UUI episodes at Week 52
* CFB in percent of Diary Days with zero UUI episodes at Week 52 in OAB Wet patients
* CFB at Week 52 in percent of dry diary days (zero UUI episodes) in OAB Wet patients
* For all OAB patients with ≥ 1 night time voids associated with urgency (NVU) at baseline, CFB at Week 52 in the average number of NVU per 24 hours
* CFB at Week 52 in overall bladder symptoms based on Patient Global Impression of Severity (PGI-Severity) in all OAB patients
* CFB at Week 52 in overall control over bladder symptoms based on Patient Global Impression of Control (PGI-Control) in all OAB patients
* CFB at Week 52 in overall symptom frequency based on Patient Global Impression of Symptom Frequency (PGI-Frequency) in all OAB patients
* CFB at Week 52 in overall urgency-related leakage over bladder symptoms based on Patient Global Impression of Urgency-Related Leakage (PGI-Leakage) in all OAB Wet patients
* Overall change of bladder symptoms based on Patient Global Impression of Change (PGI-Change) in all OAB patients at Week 52
* CFB at Week 52 in Concern Score from the OAB-q-LF (1-week recall) in all OAB patients
* CFB at Week 52 in Sleep Score from the OAB-q-LF (1-week recall) in all OAB patients
* CFB at Week 52 in Social Interaction Score from the OAB-q-LF (1-week recall) in all OAB patients
* CFB at Week 52 in scores of the Work Productivity and Activity Impairment Questionnaire-Urinary Symptoms (WPAI-US)
* CFB at Week 52 in scores of the EQ-5D in all OAB patients
* CFB at Week 52 in average number of nighttime voids for all patients
* CFB at Week 52 in average number of nighttime voids for patients with nocturia at baseline
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Czech Republic |
Estonia |
Hungary |
Latvia |
Lithuania |
Poland |
Slovakia |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 24 |