E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046494 |
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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 |
: In patients with overactive bladder (1) To investigate a dose-related reduction in average number of daily micturitions after 8 weeks of treatment with MK-0594 (0.25, 1, or 4 mg/day), compared with placebo. (2) To determine whether there is a lower incidence of dry mouth when treated with MK-0594 compared with tolterodine LA. |
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E.2.2 | Secondary objectives of the trial |
(3) To determine whether daily treatment with MK-0594 (0.25, 1, or 4 mg/day) reduces the average number of urgency (strong urge to urinate immediately) episodes, total incontinence episodes, and urge incontinence episodes, compared with placebo. (4) To investigate the improvement on exploratory endpoints after treatment with MK-0594 (0.25, 1, or 4 mg/day), compared with placebo. (5) To compare the effect of MK-0594 to tolterodine LA 4 mg on the average number of daily micturitions, urgency (strong urge to urinate immediately) episodes, total incontinence episodes, urge incontinence episodes, and on exploratory1 endpoints over 8 weeks of treatment. (6) To compare the effect of tolterodine LA 4 mg to placebo on the average number of daily micturitions, urgency (strong urge to urinate immediately) episodes, total incontinence episodes, urge incontinence episodes, and on exploratory1 endpoints over 8 weeks of treatment. (7) To determine the tolerability of MK-0594 over 8 weeks |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a. Patient agrees to participate as indicated by signing the appropriate informed consent.
b. Patient is female, aged 40 to 74 years, inclusive, with a history of no menses for at least 1 year and demonstrates serum FSH level equal to or greater than the lower limit of normal for post-menopausal women.
Note: Up to 10% patients can be male patients 40 to 74 years of age, inclusive.
c. Patient is ambulatory, is in good general physical and mental health, and appears capable of understanding and completing the study procedures including proper completion of the voiding diary.
d. History (may be verbal per patient) of urinary urgency for at least 3 months prior to Visit 1. Urodynamic evaluation is NOT required.
Visit 2 Criteria
e. In the opinion of the investigator, the patient can adequately complete a diary, as assessed by a review of the diary completed during screening.
f. The average number of micturitions calculated from the screening diary is ≥8 per diary day.
g. The average number of urge incontinence from the screening diary is ≥1 per diary day.
h. The total number of urge incontinence episodes exceeds the total number of stress incontinence episodes on the screening diary.
Visit 3 Criteria
i. In the opinion of the investigator, the patient can adequately complete a diary, as assessed by a review of the completed run-in diary
j. The average number of micturitions calculated from the run-in diary is ≥8 per diary day.
k. The average number of urge incontinence episodes from the run-in diary is ≥1 per diary day.
l. The total number of urge incontinence episodes exceeds the total number of stress incontinence episodes on the run-in diary. |
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E.4 | Principal exclusion criteria |
General Medical
a. Evidence from clinical history of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering MK-0594 to the patient, such as mental incompetence, multiple and/or severe allergies, and/or clinically unstable diseases of the cardiovascular, hepatic, renal, gastrointestinal, or hematologic systems that require further medical evaluation and/or treatment.
b. Evidence from current history of diabetes insipidus, uncontrolled hyperglycemia (fasting blood glucose >150 mg/dL, and/or non-fasting blood glucose >180 mg/dL) or uncontrolled hypercalcemia (blood total calcium >11 mg/dL).
Urologic
c. A history of injury, surgery, or neurodegenerative diseases (e.g., multiple sclerosis) that could affect the lower urinary tract or its nerve supply.
d. A history of Lower Urinary Tract Symptoms (LUTS) or Benign Prostatic Hypertrophy (BPH).
e. A history of rectal incontinence.
f. A history of continual urine leakage or patient is unaware of urine leakage.
g. A history of surgery to correct stress urinary incontinence or prolapsed uterus within 6 months.
h. Bladder training or electrostimulation within 2 weeks prior to Visit 1 or plans to initiate during the study.
i. Active or recurrent (>6 episodes per year) urinary tract infections by clinical history, clinical symptoms, or laboratory criteria (≥5 WBC or ≥20 bacteria per high-powered field in a spun specimen and/or a positive urine culture defined as ≥105 colony forming units (CFU)/mL in 1 specimen).
j. Requirement for an indwelling catheter or intermittent catheterization.
Medications
k. Patient is not willing to discontinue any of the following therapies at least 3 weeks prior to Visit 2 and remain off the therapy for the duration of the study:
Anticholinergics including but not limited to oxybutynin, tolterodine, trospium, darafenacin, hyoscyamine, and propantheline.
Smooth muscle relaxants including but not limited to flavoxate, dicyclomine, propiverine.
l. Patient is receiving therapy with any of the following medications for less than 8 weeks prior to Visit 1 or plans to initiate or change therapy during the study.
Tricyclic antidepressants or combinations including but not limited to amitriptyline, imipramine, and doxepin.
Seretonin and/or norepinephrine reuptake inhibitors including but not limited to duloxetine.
Calcium channel blockers including but not limited to nimodipine and nifedipine.
Alpha-adrenergic agonists including but not limited to ephedrine and pseudoephedrine.
Diuretic therapy including but not limited to furosemide and hydrochlorothiazide.
m. Patient is receiving systemic or topical hormone replacement therapy including but not limited to estrogen and estrogen/progesterone combination products for less than 12 weeks prior to Visit 1 or plans to initiate or change therapy during the study.
n. Patient has used any medication with a narrow therapeutic window, including but not limited to warfarin (COUMADIN, DuPont Pharma) and digoxin within 4 weeks prior to Visit 1.
o. Patient has used medications with known activities as strong inhibitors cytochrome P-450 3A4 (CYP3A4) (see Appendix 10), or any other medication that may pose a risk to the patient when combined with tolterodine within 4 weeks prior to Visit 1.
p. Patient previously received MK-0594 or used any investigational drug in the 1 month prior to Visit 1.
q. Patient is receiving desmopressin or other medications with antidiuretic effects. |
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E.5 End points |
E.5.1 | Primary end point(s) |
: In patients with overactive bladder (1) To investigate a dose-related reduction in average number of daily micturitions after 8 weeks of treatment with MK-0594 (0.25, 1, or 4 mg/day), compared with placebo. (2) To determine whether there is a lower incidence of dry mouth when treated with MK-0594 compared with tolterodine LA. |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |