Efficacy of Intracavernosal as add-on Therapy to Sildenafil 100 mg on Demand Compared to Sildenafil 100 mg on Demand for the Treatment of Erectile Dysfunction (ED) Not Sufficiently Responsive to Standard Therapy With Phosphodiesterase Type 5 Inhibitors

NCT05196308 | Completed Phase 2

• 2 other identifiers: APHP2110422021-005496-39
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to investigate the efficacy of intracavernosal (Xeomin®) (100U) as add-on therapy to sildenafil 100 mg on demand in men with ED and insufficient response to standard therapy with 100 mg sildenafil on demand during the 4-week open-label run-in phase. The secondary objectives are to further describe the efficacy and safety of (Xeomin®) 100U IC as add-on therapy to sildenafil 100 mg on demand:

• i) a log diary five-item questionnaire completed after each sexual attempt (Sexual Encounter Profile);
• ii) a self-reporting measure that scores erection hardness on a 4 point scale completed after each sexual attempt;
• iii) The Global Assessment Question.
• to assess effect persistence at month 6 and month 9.
• to assess safety of (Xeomin®) 100U IC in combination with sildenafil 100 mg on demand.

Conditions

Erectile Dysfunction

Keywords

Erectile Dysfunction; phosphodiesterase type 5 inhibitors; efficacy

Outcome Measures

Primary Outcomes (3)

• Change in the erectile function

  Change in the erectile function between baseline and month 3, measured by the International Index of Erectile Function - Erectile Function domain score (IIEF-EF). The International Index of Erectile Function (IIEF) is a 15-item self-report instrument assessing male sexual function. The Erectile Function (EF) domain score of the IIEF, comprised of items 1 to 5 and 15 from the IIEF, is used in this study.

  at baseline and month 3

• Change in SEP2

  Question providing information as whether the erection is hard enough to penetrate (SEP2). The SEP is a log diary with 5 questions answered after each sexual intercourse attempt, providing information as to whether the erection was hard enough to penetrate (SEP 2), or whether it was maintained for completion (SEP 3) or a satisfactory sexual experience (SEP 4).

  at baseline and month 3

• Change in SEP3

  Question providing information as duration of erectile. The SEP is a log diary with 5 questions answered after each sexual intercourse attempt, providing information as to whether the erection was hard enough to penetrate (SEP 2), or whether it was maintained for completion (SEP 3) or a satisfactory sexual experience (SEP 4).

  at baseline and month 3

Secondary Outcomes (4)

• Change in SEP 4 score

  at baseline and month 3

• The Erection Hardness Score (EHS)

  at baseline and month 3

• Global Assessment Question (GAQ)

  at baseline and month 3

• Persistence of efficacy

  at 6- and 9- month

Study Arms (2)

Xeomin® receivers

EXPERIMENTAL

Patients will receive Xeomin®.

Drug: Investigational product administration Xeomin® (MERZ PHARMACEUTICALS GMBH)

Placebo receivers

PLACEBO COMPARATOR

Patients will receive placebo injection instead of Xeomin®.

Drug: Placebo administration

Interventions

Investigational product administration Xeomin® (MERZ PHARMACEUTICALS GMBH) DRUG

Administration of the investigational product. For the double-blind treatment phase, experimental group : Patients will receive Xeomin® (MERZ PHARMACEUTICALS GMBH), 100 U, a paired intracavernosal injection to be performed by the investigator.

Xeomin® receivers

Placebo administration DRUG

For the double-blind treatment phase, control group : Patients will receive placebo of Xeomin® 100 U, a paired intracavernosal injection is to be performed by the investigator.

Placebo receivers

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: Male subject aged ≥18 to ≤ 80 years at visit1
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects have to fulfill all of the following criteria before being included in the open-label run-in phase:
• Written informed consent obtained from the subject
• History of ED for at least 6 months prior to screening, defined as "the inability to achieve and maintain an erection of the penis sufficient to complete satisfactory sexual intercourse" (NIH), the diagnosis of ED has to be confirmed by a physician
• Understanding of study procedures and willingness to abide by all procedures during the course of the study
• Male subject aged ≥18 to ≤ 80 years at visit 1
• Have a monogamous relationship with a female sexual partner (vaginal penetration required for several of the primary efficacy variables) for at least 6 months prior to screening
• Highly motivated to obtain treatment for ED
• History of previous use of at least 1 marketed PDE5 inhibitor and insufficient therapeutic efficacy despite use of the highest approved dose
• Subjects have to fulfill all of the following criteria before being included in the double blind treatment phase:
• At least 4 attempts at sexual intercourse during the open-label run-in phase with use of 100 mg sildenafil approximately 1 hour before attempting intercourse
• IIEF-EF score \<17
• At least 50% of attempts at sexual intercourse during the open-label run-in phase had been unsuccessful i.e. the following question in the Subject Diary had to be answered with "No":
• "Did your erection last long enough for you to have successful intercourse?" (SEP3: success in maintenance of erection)
• Highly motivated to obtain treatment for ED according to the investigator judgment
• Ability to understand and follow study-related instructions

You may not qualify if:

• Hypersensitivity to the active substance (Clostridium Botulinum neurotoxin type A) or to any of the excipients (Human albumin, sucrose)
• BW \<50 kg
• ED caused by other primary sexual disorders including premature ejaculation or ED caused by untreated endocrine disease (eg, hypopituitarism, hypothyroidism, or hypogonadism)
• History of penile implant.
• The presence of clinically significant penile deformity in the opinion of the investigator.
• Patients with chronic stable angina treated with long-acting nitrates, or patients with chronic stable angina who have required short-acting nitrates in the last 90 days, or angina occurring during sexual intercourse in the last 6 months.
• Patients having met the criteria for unstable angina within 6 months prior to Visit 1, history of myocardial infarction or coronary artery bypass graft surgery within 90 days prior to Visit 1, or percutaneous coronary intervention (eg, angioplasty or stent placement) within 90 days prior to Visit 1.
• Any supraventricular arrhythmia with an uncontrolled ventricular response (mean heart rate \>100 bpm) at rest despite medical or device therapy, or any history of spontaneous or induced sustained ventricular tachycardia (heart rate \>100 bpm for 30 sec) despite medical or device therapy, or the presence of an automatic internal cardioverter-defibrillator.
• A history of sudden cardiac death (arrest) despite medical or device therapy.
• Any evidence of congestive heart failure within 6 months prior to Visit 1.
• A significant conduction defect within 90 days prior to Visit 1.
• Systolic blood pressure \>170 or \<90 mm Hg or diastolic blood pressure \>100 or \<50 mm Hg at screening (if stress is suspected, retest under basal conditions), or patients with malignant hypertension.
• \<12 weeks since most recent injection of BTX-A/B into any body region for any indication
• Neurological disorder associated with neuro muscular dysfunction of any kind in medical history.
• Planned concomitant treatment with BTX -A/B of any body region during the study.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Neuro-Urology-Andrology, Physical Medicine and Rehabilitation Department, Raymond Poincaré Hospital, APHP

Garches, 92380, France

Location

Related Publications (3)

• Fisher WA, Gruenwald I, Jannini EA, Lev-Sagie A, Lowenstein L, Pyke RE, Reisman Y, Revicki DA, Rubio-Aurioles E. Standards for Clinical Trials in Male and Female Sexual Dysfunction: III. Unique Aspects of Clinical Trials in Male Sexual Dysfunction. J Sex Med. 2017 Jan;14(1):3-18. doi: 10.1016/j.jsxm.2016.08.016.

  PMID: 28065358 BACKGROUND

• Mulhall JP, Goldstein I, Bushmakin AG, Cappelleri JC, Hvidsten K. Validation of the erection hardness score. J Sex Med. 2007 Nov;4(6):1626-34. doi: 10.1111/j.1743-6109.2007.00600.x. Epub 2007 Sep 21.

  PMID: 17888069 BACKGROUND

• Giuliano F, Denys P, Joussain C. Effectiveness and Safety of Intracavernosal IncobotulinumtoxinA (Xeomin(R)) 100 U as an Add-on Therapy to Standard Pharmacological Treatment for Difficult-to-Treat Erectile Dysfunction: A Case Series. Toxins (Basel). 2022 Apr 16;14(4):286. doi: 10.3390/toxins14040286.

  PMID: 35448895 DERIVED

MeSH Terms

Conditions

Erectile Dysfunction

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Study Officials

• François GIULIANO, MD, PhD

  Neuro-Urology-Andrology, Raymond Poincaré Hospital, APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: January 19, 2022
• Study Start: March 18, 2022
• Primary Completion: July 23, 2024
• Study Completion: November 15, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)