Effects of Single Dose Tadalafil on Urethral and Anal Closure Function

NCT05095077 | Completed Phase 1

• 2 other identifiers: PDE5I-UPR-AAR-012020-005839-76
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Urinary Incontinence,Stress; Fecal Incontinence

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Tadalafil

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Tadalafil 40 MG DRUG

Single dose on study day 1/2

Tadalafil

Placebo DRUG

Identical to active IMP

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital Bispebjerg and Frederiksberg: lead

Study Sites (1)

Zelo Phase 1 unit

Copenhagen, 2400, Denmark

Location

MeSH Terms

Conditions

Urinary Incontinence, Stress; Fecal Incontinence

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Urinary Incontinence; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Thea Christoffersen

  Zelo Phase 1 unit, University Hospital Bispebjerg and Frederiksberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The tadalafil tablets and placebo are over-encapsulated in identical hard-gelatin capsules. The over-encapsulation, packaging and labelling is performed by the hospital pharmacy.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Principal Investigator

Model Details: Two-period (AB/BA) crossover study

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: October 27, 2021
• Study Start: August 1, 2021
• Primary Completion: December 30, 2021
• Study Completion: January 1, 2022
• Last Updated: April 6, 2022

Record last verified: 2022-04

Locations

DK (1)