Effects of Single Dose Tadalafil on Urethral and Anal Closure Function

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

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.

Study Overview

• Status: Completed
• Conditions: Fecal Incontinence; Urinary Incontinence,Stress
• Intervention / Treatment: Drug: Tadalafil 40 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Zelo Phase 1 unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tadalafil; 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; Single dose on study day 1/2
PLACEBO_COMPARATOR: 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.	Drug: Placebo; Identical to active IMP

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Bispebjerg and Frederiksberg
• Investigators: Principal Investigator: Thea Christoffersen, Zelo Phase 1 unit, University Hospital Bispebjerg and Frederiksberg

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2021
• Primary Completion (ACTUAL): December 30, 2021
• Study Completion (ACTUAL): January 1, 2022

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (ACTUAL): October 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Gastrointestinal Diseases; Urination Disorders; Intestinal Diseases; Rectal Diseases; Urinary Incontinence; Urinary Incontinence, Stress; Fecal Incontinence; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: PDE5I-UPR-AAR-01; 2020-005839-76 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No