Effects of Single Dose Tadalafil on Urethral and Anal Closure Function

Phase 1

Completed

• Conditions: Fecal Incontinence; Urinary Incontinence,Stress
• Interventions: Drug: Tadalafil 40 MG; Drug: Placebo

• Registration Number: NCT05095077
• Lead Sponsor: University Hospital Bispebjerg and Frederiksberg

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-08-01
• Study First Submitted: 2021-08-26
• Study First Submitted QC: 2021-10-13
• Study First Posted: 2021-10-27
• Primary Completion: 2021-12-30
• Study Completion: 2022-01-01
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-04
• Last Update Posted: 2022-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 24

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Tadalafil	Tadalafil 40 MG	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.
Placebo	Placebo	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Difference in average UOP-tadalafil and average UOP-placebo during squeezing.	2-hours post-dose
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 anal opening pressure (AOP) after administration of 40 mg tadalafil compared to AOP after placebo (during relaxation).
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

Trial Locations

Locations (1)

Zelo Phase 1 unit; 🇩🇰 Copenhagen, Denmark