Effects of Single Dose Tadalafil on Urethral and Anal Closure Function

Study Overview
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Brief Summary
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The purpose of the trial is to assess the effect of tadalafil compared to placebo (inactive comparator) on the urethral - and anal pressure and on urine flow in healthy females. Further, the purpose of the trial is to evaluate the potential for going forward with studies of tadalafil in patients suffering from urine or fecal incontinence.

Official Title
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Effects of Single Dose Tadalafil on Urethral and Anal Closure Function and on Urinary Flow in Healthy Females: A Randomised, Controlled, Double-blinded, Two-period Cross-over Study

Conditions
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Urinary Incontinence,Stress, Fecal Incontinence

Intervention / Treatment
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* Drug: Tadalafil 40 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Normal weight (Body weight 50 kg or more, Body Mass Index 18-5-30 kg/m2) Sexual abstinence or use of safe contraceptive methods i.e. intrauterine devices, hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long acting injections), or surgically sterilized partner throughout the course of the study and until six days after the study has ended for the subject. Women who are postmenopausal (defined as no menstrual periods for 12 months or more prior to enrolment) can be included without use of contraceptive methods. Presentation of a negative urine human chorionic gonadotropin (hCG) urine pregnancy test prior to dosing (on both study days) Exclusion Criteria: History of clinically significant urinary incontinence. Current acute or chronic condition, unless considered clinically irrelevant and stable by the investigator. Average systolic blood pressure <100 mmHg or >140 mmHg and/or average diastolic blood pressure <60 mmHg or >90 mmHg (average of three measurements performed at screening). Average pulse < 40 or > 100 beats/minute (average of three measurements performed at screening). Pregnancy within 6 months before screening and throughout the study period. Breastfeeding throughout the study period and 6 days after study day 2. Any systemic drug use within 2 weeks before first study drug administration (prescription drugs, over-the-counter drugs, herbal drugs and illicit drugs), except for occasional use of paracetamol (up to 4 g/day), hormonal contraceptives and hormone replacement therapy. Smoking or other regular use of any form of nicotine product during the study period and the previous 3 months. Alcohol consume 24 hours prior to dosing. Current or prior participation (within 3 months before screening) in other clinical trials that might affect the results of this study (judged by the investigator).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Two-period (AB/BA) crossover study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil<br>Subjects are randomized to either 40 mg tadalafil on study day 1 and placebo on study day 2, or placebo on study day 1 and 40 mg tadalafil on study day 2. | Drug: Tadalafil 40 MG<br>* Single dose on study day 1/2<br>|
| Placebo Comparator: Placebo<br>Subjects are randomized to either 40 mg tadalafil on study day 1 and placebo on study day 2, or placebo on study day 1 and 40 mg tadalafil on study day 2. | Drug: Placebo<br>* Identical to active IMP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo-corrected change in opening urethral pressure after single dose tadalafil | Difference in average urethral opening pressure (UOP) after administration of 40 mg tadalafil (UOP-tadalafil) compared to UOP after placebo (during relaxation). | 2 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in average anal opening pressure (AOP) after administration of 40 mg tadalafil compared to AOP after placebo (during relaxation). | Difference in average anal opening pressure (AOP) after administration of 40 mg tadalafil compared to AOP after placebo (during relaxation). | 2-hours post-dose | 
| Difference in average UOP-tadalafil and average UOP-placebo during squeezing. |  | 2-hours post-dose | 
| Difference in average AOP-tadalafil and average AOP-placebo during squeezing. |  | 2-hours post-dose | 
| Elastance (opening/closing) during relaxation and squeezing (tadalafil compared to placebo). |  | 2-hours post-dose | 
| Difference in maximum urine flow rate (Qmax) and average urine flow rate (Qave) after tadalafil and placebo administration, respectively. |  | 2-hours post-dose |