Efficacy of Intracavernosal Xeomin With Tadalafil for Mild-Moderate Erectile Dysfunction

Clinical Efficacy of Intracavernosal Xeomin as an Adjunctive Therapy to on Demand Tadalafil 20 mg for the Treatment of Mild to Moderate Erectile Dysfunction: A Randomized Crossover Pilot Study

Erectile dysfunction (ED) affects approximately 30 million men in the United States and is associated with factors such as aging, smoking, diabetes, hypertension, obesity, and sedentary lifestyle. ED can also negatively impact the quality of life of patients and their partners. Treatment decisions are typically made jointly between patients and their urologists, often starting with less invasive options. Oral phosphodiesterase-5 inhibitors (PDE5 inhibitors), including sildenafil, tadalafil, and vardenafil, are commonly used as first-line therapy. While these medications improve erectile function in many patients, approximately 30-40% do not respond adequately to PDE5 inhibitor therapy alone. Patients who do not achieve sufficient benefit may require additional or more invasive treatment options.

Study Overview

• Status: Not yet recruiting
• Conditions: Erectile Dysfunction
• Intervention / Treatment: Other: Placebo; Drug: IncobotulinumtoxinA (100 Units); Drug: Tadalafil 20 MG

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Hypersensitivity to the active substance (Clostridium Botulinum neurotoxin type A) or to any of the excipients (Human albumin, sucrose)
• BW <50 kg
• Diagnosis of spinal cord injury
• ED caused by other primary sexual disorders including premature ejaculation or ED caused by untreated endocrine disease (e.g., hypopituitarism, hypothyroidism, or hypogonadism)
• History of penile implant.
• The presence of clinically significant penile deformity in the opinion of the investigator.
• Concomitant diagnosis of Peyronie's disease
• 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 (e.g., 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.
• Known hypersensitivity to human serum albumin, sucrose, or the active substance BTX-A.
• Generalized disorders of muscles activity (e.g. myasthenia gravis, Lambert-Eaton-Syndrome, amyotrophic lateral sclerosis) or any other significant peripheral neuromuscular dysfunction which might interfere with the study.
• Any condition that would interfere with the patient's ability to provide informed consent or comply with study instructions, would place patient at increased risk, or might confound the interpretation of the study results.
• Current treatment with nitrates (as outlined in previous Exclusion Criterion, cancer chemotherapy, or anti-androgens.
• History of drug, alcohol, or substance abuse within the past 6 months.
• Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• Treatment within the last 30 days with a drug or device that has not received regulatory approval at the time of study entry.
• Ongoing severe or uncontrolled systemic disease, current malignancy, hemophilia, or HIV infection in medical history.
• Severe or uncontrolled respiratory disease in medical history.
• Evidence or suspicion that the subject is not willing or unable (e.g. Due to severe cognitive communication impairment) to understand the information that is given to him as part of the informed consent, in particular regarding the risks and discomfort which he would agree to be exposed to.
• Any reason which in the investigator's opinion is likely to compromise the subject's ability to participate in the study.
• Subject who is imprisoned or is lawfully kept in an institution
• Participation in a clinical study within 12 weeks prior to screening or planned participation during this study.
• Previous participation in this clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xeomin + PDE5i; Subjects in this portion of the trial will be administered 20 mg of Tadalafil in conjunction with 100 units of Xeomin	Drug: IncobotulinumtoxinA (100 Units); Intracavernosal Xeomin; Drug: Tadalafil 20 MG; PDE5 Inhibitor Medication
Placebo Comparator: Placebo + PDE5i; Subjects in this portion of the trial will be administered 20 mg of Tadalafil in conjunction with a placebo	Other: Placebo; Placebo; Drug: Tadalafil 20 MG; PDE5 Inhibitor Medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in erectile function	Change in erectile function as measured by the validated IIEF-EF domain (3-6 months) following Xeomin portion of the crossover study. This domain provides a score on a scale of 6-30, where scores can be interpreted as follows: 26-30: No Erectile Dysfunction; 22-25: Mild Erectile Dysfunction; 17-21: Mild to Moderate Erectile Dysfunction; 11-16: Moderate Erectile Dysfunction; 6-10: Severe Erectile Dysfunction	3-6 months
Change in erectile hardness	Change in erectile hardness as measured by the validated erectile hardness scale (EHS) (3-6 months) following Xeomin portion of the crossover study. The scale ranges from Grade 0 - Grade 4. It measures the firmness of an erection using the following grade interpretation: Grade 0: Penis does not enlarge.; Grade 1: Penis is larger, but not hard.; Grade 2: Penis is hard, but not hard enough for penetration.; Grade 3: Penis is hard enough for penetration, but not completely hard.; Grade 4: Penis is completely hard and fully rigid	3-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence of efficacy in erectile function	Persistence of efficacy in erectile function as measured by the validated IIEF-EF domain (3-6 months in placebo portion of crossover study). This domain provides a score on a scale of 6-30 over a period of time, where scores can be interpreted as follows: 26-30: No Erectile Dysfunction; 22-25: Mild Erectile Dysfunction; 17-21: Mild to Moderate Erectile Dysfunction; 11-16: Moderate Erectile Dysfunction; 6-10: Severe Erectile Dysfunction	3-6 months
Persistence of efficacy in erectile hardness	Persistence of efficacy in erectile hardness as measured by the validated erectile hardness scale (EHS) (3-6 months in placebo portion of crossover study). The scale ranges from Grade 0 - Grade 4. It measures the firmness of an erection over a period of time using the following grade interpretation: Grade 0: Penis does not enlarge.; Grade 1: Penis is larger, but not hard.; Grade 2: Penis is hard, but not hard enough for penetration.; Grade 3: Penis is hard enough for penetration, but not completely hard.; Grade 4: Penis is completely hard and fully rigid	3-6 months

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Merz North America, Inc.

Publications and helpful links

General Publications

• Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh J, Khera M, McVary KT, Miner MM, Nelson CJ, Sadeghi-Nejad H, Seftel AD, Shindel AW. Erectile Dysfunction: AUA Guideline. J Urol. 2018 Sep;200(3):633-641. doi: 10.1016/j.juro.2018.05.004. Epub 2018 May 7.
• Abou Zahr R, Bou Kheir G, Mjaess G, Jabbour T, Chalhoub K, Diamand R, Roumeguere T. Intra-Cavernosal Injection of Botulinum Toxin in the Treatment of Erectile Dysfunction: a Systematic Review and Meta-Analysis. Urology. 2022 Dec;170:5-13. doi: 10.1016/j.urology.2022.08.039. Epub 2022 Sep 15.
• Giuliano F, Joussain C, Denys P, Laurin M, Behr-Roussel D, Assaly R. Intracavernosal OnabotulinumtoxinA Exerts a Synergistic Pro-Erectile Effect When Combined With Sildenafil in Spontaneously Hypertensive Rats. J Sex Med. 2022 Jun;19(6):899-906. doi: 10.1016/j.jsxm.2022.03.213. Epub 2022 Mar 29.
• Giuliano F, Joussain C, Denys P. Safety and Efficacy of Intracavernosal Injections of AbobotulinumtoxinA (Dysport(R)) as Add on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 for Erectile Dysfunction-Case Studies. Toxins (Basel). 2019 May 21;11(5):283. doi: 10.3390/toxins11050283.
• Giuliano F, Joussain C, Denys P. Long Term Effectiveness and Safety of Intracavernosal Botulinum Toxin A as an Add-on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 Injections for Erectile Dysfunction. J Sex Med. 2022 Jan;19(1):83-89. doi: 10.1016/j.jsxm.2021.10.011. Epub 2021 Dec 20.
• 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.
• Giuliano F, Denys P, Joussain C. Safety and Effectiveness of Repeated Botulinum Toxin A Intracavernosal Injections in Men with Erectile Dysfunction Unresponsive to Approved Pharmacological Treatments: Real-World Observational Data. Toxins (Basel). 2023 Jun 5;15(6):382. doi: 10.3390/toxins15060382.
• Lowe G, Bahnson R. Non-invasive management of primary phosphodiesterase type 5 inhibitor failure in patients with erectile dysfunction. Ther Adv Urol. 2009 Dec;1(5):235-42. doi: 10.1177/1756287210362069.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: April 12, 2026
• First Submitted That Met QC Criteria: April 12, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: xeomin; Incobotulinumtoxin A
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Mental Disorders; Genital Diseases, Male; Male Urogenital Diseases; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Erectile Dysfunction; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Indole Alkaloids; Heterocyclic Compounds, 3-Ring; Carbolines; Tadalafil; incobotulinumtoxinA
• Other Study ID Numbers: IIT12255

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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