Apomorphine SL for the treatment of erectile dysfunction in patients with spinal cord injury

373 LONG-TERM

SAFETY

EXPERIENCE

,

Montorsi F.‘. Verheyden B. Watkins V-

Jiinemann

WITH

TADALAFIL

K.‘, Moncada

Li, Valiquettc

L.‘. Drnnc

.I.*.

‘Universna Vita e Salute San Raffaele, Urology, Milan, Italy, ‘Unwersitair Ziekenhuls Mannheim, Urology. Antwerpen, Urologic, Antwerp, Belgium. ‘UniversitBtsklinikum Mannheim, Germany, ‘Hospital Gregorio Maranon, Urology, Madrid, Spain, ‘Centre Hospitalier de I’Universite de MO. HBpital St. Luc, Montreal, Canada, “Eli Lilly and Company, Statistics, Indianapolis, Indiana, United States of America, ‘Eli Lilly and Company, Clinical Research, Indianapolis, Indiana, United States ofAmerica INTRODUCTION & OBJECTIVES: Tadalafil (CialisTM) is a potent and selective Inhibitor of phosphodiesterase type 5 (PDES) being mvestigated for the treatment of erectile dysfunction (ED). This study was designed to assess the long-term safety and tolerability of tadalafil in a broad range of patients with ED. MATERIAL & METHODS: Patients who had previously partlclpated in one of five placebo-controlled safeety and efficacy studies of tad&Al were eligible for enrolment in this ongoing, la-month, international, multicentre, open-label study. All patients started on tadalafil IO mg, regardless of the dose received m their previous study. and took tadalatil as needed (maximum one dose/day). Investigators could increase the dose to 20 mg if they determined that the oatient could not achieve satisfactory intercourse after an adeauate number of sexual attimpts. A dose reduction could be made from 20 mg lo IO mg or &om 10 mg to 5 mg if an adverse event was persistent or interfered with daily activity and was iudged bv the investieator to be related to tad&&l. Patients were encouraged to remain on a d&e assigned at a scheduled study visit until at least the next study visz; however, dose modifications could be made at unscheduled visits ifnecessary Exposure and the Incidence of treatment-emergent adverse events, discontinuatmns due to adverse events (AEs), and deaths were assessed. Pre-existing conditions and severity, for determination of treatment emergence, were based on chroniz conditions and events actually present at the enrolment visit for this studv. All analvses have been nerfonned on data collected through 1 November 2001. RESULTS: A total of 1173 patients enrolled m this trial. Their mean age was 57 (*IO) years. At the time of this analysis, 970 (82.7%) patients had at some time titrated up to tadalafil 20 mg. During the study, 870 patients were exposed to >I0 mg tadalafil for at leas1 I year, of whom 574 were exposed to tadalafil 20 mg for at least 1 year. Furthermore, 991 patients were exposed to >I0 mg tadalafil for at least 6 months, of whom 721 were exposed io tadalafil 20 kg for at least 5 months. The most frequently reported (?5%) treatmentemereent AEs were headache (15.3%). dvsnensia (11.0%). infection (10.1%). back nain (7.3%), rhinitis (6.5%), flu synhrome (&.2%j, iain (6.l%), and surgical pro&lure (6.&X). Overall, 5.4% of patients discontinued due to AEs. The discontinuation rate for any individual AE was ~1%. Three deaths occurred during the conduct of the studv. none of which was judged by the investigator to be related to tadalafil treatment

374 “REAL UNDER FLEXIBLE DOSING. VARDENAFIL IMPROVED ERECTILE POPULATION OF MEN

WORLD” FUNCTION

CONDITIONS. IN A BROAd

Potemoa A.J.‘, Bernard I.“, Ulbrich E.? ‘Private Practice, Munich,

&many,

‘Bayer Vital, Medical,

Leverkuscn,

Germany

INTRODUCTION & OBJECTIVES: Vardcnafil is a potent and highly selective PDE5 inhibitor under investigation for the treatment of erectile dysfunction (ED). In this study, the safety, tolerability, and efficacy of flexible doses of vardenafil were determined. MATERIAL & METHODS: In this multicentre, open label study conducted in Germany and France, 390 of 423 enrolled men with ED initiated treatment with vardenafil. Patients started at IO mg vardenatil as needed and doses were adjusted to 5 mg or 20 mg at 2 and 6 weeks. 366 patients were included in the ITT, LOCF analysis. Efficacy parameters included answers to the Global Assessment Question (GAQ), answers to the patient diary questions on penetration (SEP2) and maintenance (SEP3), and the IIEF Erectile Function (EF) domain score. RESULTS: Overall, 91.8% of men reported improved erections (CrAQ; LOCF). In addition, overall per-patient success rates for penetration and erection maintenance wcrc 90.4% and 8 I. I %, respectively. EF domain scores had markedly increased by week 6 and were maintained to week IO. Those who remained on vardenatil 10 mg for the duration of the study showed the greatest response (see table). All regimens were generally well tolerated and adverse events (AEs) were mild to moderate in Intensity. Only 0.5% of patients titrated down to 5 mg. The most frequent AEs were headache (huh), flushing (6%). dyspepsia (2%) and rhinitis (2%).

CONCLUSIONS: In this long-term, open-label study. tadalafil showed good wfety and tolerability for the treatment of ED m a broad range of patients.

CONCLUSIONS: Vardenafil improved erectilc function, on average to close to normal function. Patients remaining on vardenatil IO mg throughout the study returned to normal erectile function. However, for those who chose to increase the dose from IO mg to 20 mg, a further improvement in EF Domain score was seen. Under these more “real world” conditions, in this broad population of ED patients. vardenatil was eflicacious and well-tolerated.

375

376

A

PILOT

STUDY

SILDENAFIL

USING

(VIAGRA)

SUBLINGUAL

APOMORPHINE

IN

APOMORPHINE

DYSFUNCTION

NON-RESPONDERS

SL FOR THE TREATMENT IN PATIENTS WITH SPINAL CORD

Strebel R.‘. ReltL A.>. Tcnti (;. Kalsi J.S.‘. MuneerA.‘,

Kell P.‘, Minhas

‘The Institute of Urology,

Urology,

lslington

London.

NHS Trust, Gum,

INTRODUCTION

S.‘. Ralph

London.

The aim of this pilot

United

Kingdom.-

‘Camden

study

was

in the management

MATERIAL

& METHODS:

to evaluate

the efficacy

of sublingual

in these patients.

Failures were defined as no benefit over baseline 30 men (mean age 58.2

over 8 weeks.

(3mg)

over a period of 8 weeks. The International

(IIEF)

questionnaire

and the global assessment

RESULTS:

All 30 patients side effect.

Although domain

there

Dysfimction

queition (GAQ) were used to assess the

scores,

medication.

management

completed

All patients

was an improvement the difference

CONCLUSIONS:

Sublingual

This

pilot

of patients

However, f&her European

Index of Erectile

of treatment.

commonest

study

the study; reported

did not reach statistical

apomorphine

who have

is

it may

failed

mild

improved

in the mean

suggests

Switzerland.

‘Balgrist

MATERIAL & METHODS: 22 patients (mean age 38 years (range 22-59) with a chronic SC1 and neurogenic erectile dysfunction were included in the study and underwent physical examination according to ASIA standards. Complete videourodynamical work-up were done and neurophysiological evaluation included somatosensory evoked potentials of the pudendal nerve, palmar and plantar sympathetic skin responses and bulbocavernous reflex recordings. Thereafter the patients received 8 units of apomorphine SL 3 mg for sublingual administration and were asked to complete IIEF-questionnaires before and after treatment. Side effects, and subjective efficacy compared to other treatment options advantages/disadvantages of the sublingual administration were recorded.

years range 20-79 years) were instructed to take 8 tablets of apomorphine

eficacy

D.‘, Schurch B.:

Sildenatil is a highly effective treatment

of erectile dysfunction

after taking 8 tablets of 1OOmg sildenafil

llauri

of Urology, Zurich. Zurich, Swuzerland

INTRODUCTION & OBJECTIVES: To evaluate the effectiveness of apomorphinc SI. 3 mg to treat erectile dysfunction in pabents with spinal cord mjury (SCI). To determine possible differences in efficacy considering chnical, urodynamical and neurophyhiological findings.

Kingdom

although 20-30% of patients may fail to gain a benefit.

apomorphine

. CurtA.‘,

‘University Hospital, Department University Ilospital, Neuro-Urology, and

United

&OBJECTIVES:

for erectile dysfunction,

D.J.’

OF ERECTILE INJURY

nausea

(8%) being

erections

IIEF

the

to the CrAQ.

and erectile

timction

significance.

a safe have

and

well-tolerated

limited

to gain benefit

role

from

studies with larger numbers of patients are required.

Urology Supplements 2 (2003) No. 1, pp. 96

in the

sildenafil.

RESULTS: I1 patients had upper motoneuron lesions (UMN), (6 complete, 5 incomplete). 9 patients presented with lower motoneuron lesions (LMN) (7 complete, 2 incomplete) and 2 patients showed mixed lesions. 7 patients experienced a certain degree of response and reported that the drug helped them in getting an erection (4 out of 9 with LMN lesions, 2 out of I I with UMN lesions and one with’ a mixed lesion). However, only 2 patients reported erections suff?zient for intercourse (both with clinical and neurophysiological complete LMN). 9 patients reported side effects (4 with nausea and 5 with cardiovascular symptoms). 3 patients stopped taking medication because of intolerable side effects. 20 out of 22 patients preferred sublingual instead of oral administration. Only 2 out of 22 would agree to continue apomorphine SL as their standard treatment, all other were in fact disappointed.

.

CONCLUSIONS: Activation of dopamine receptors in the human brain and spinal cord has been shown to elicits penile erection mediated by a complex mechanism. In our study, dopamine agonists such as the DliD2 receptor agonist apomorphine, mainly facilitate erectile function in patients with a lesion of the sacral spinal erection centre but preserved thoracolumbar erection centre, allowing centrally induced erections. The significance of a certain response in SC1 patients with UMN lesions is unclear and might be attributable to D2 receptors in the spinal cord, which has been recently shown in animals. However, the overall low response rate and the considerable side effects suggest apomorphine as a non valuable therapy for crectile dysfunction in SC1 patients.