Ultrasound Doppler Measurements of Penile Blood Flow as a Predictor of Clinical Efficacy

Introduction: Historically, ultrasound doppler measurements of penile blood flow have been used to assess degrees of Erectile Dysfunction of mixed aetiology. Objective: To determine if Ultrasound Doppler measurements of penile blood flow could be a useful predictive Phase 1 pharmacodynamic tool in dose optimization, and could correlate with clinical efficacy. Methods: This study assessed an experimental topical gel based on glyceryl trinitrate (GTN) at a variety of doses by measuring haemodynamic changes within penile cavernosal arteries. A placebo controlled, double-blind, dose ranging, cross over study was conducted in 15 healthy, adult men. Doses of GTN studied were 0.01, 0.075, 0.25 and 0.6mg, and were applied to the glans penis. Results: Significant differences in penile blood flow (haemodynamics) were noted only in the 0.6mg dose although 0.25mg showed some directional improvement. At the 0.6mg dose the most prominent haemodynamic changes were seen with regard to diastolic velocity, pulsatility index and overall waveform which would be positively associated with the ability to obtain an erection. All doses were well tolerated and there was no clear evidence of headache as a drug related adverse event. No fall in blood pressure or symptoms associated with hypotension were reported. On this basis the 0.6mg dose was chosen for a Phase II(a) study, previously reported in J Sex. Med 2018; 15:167-175, and shown to be superior to placebo in the primary endpoint of the IIEF-EF domain in 230 patients. The product was very well tolerated with only 18 instances of headache in 1003 intercourse attempts (14 considered to be related to treatment). Conclusion: Ultrasound Doppler measurements of penile blood flow has been shown to be a useful predictive Phase 1 pharmacodynamic tool in dose optimization, and correlates well with clinical efficacy. Disclosure: Work supported by industry: yes, by Futura Medical Developments Ltd. A consultant, employee (part time or full time) or shareholder is among the authors (Futura Medical Developments Limited).