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Tadalafil Once-a-day: Why, When, for Whom?. Contents. Modern management of erectile dysfunction Why the Once-Daily/Once-a-day (OAD) Alternative to On-Demand Dosing in Erectile Dysfunction (ED) Tadalafil OAD Efficacy in ED Tadalafil OAD Safety and Tolerability in ED

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Tadalafil once a day why when for whom

Tadalafil Once-a-day:

Why, When, for Whom?


Tadalafil once a day why when for whom

Contents

  • Modern management of erectile dysfunction

  • Why the Once-Daily/Once-a-day (OAD) Alternative to On-Demand Dosing in Erectile Dysfunction (ED)

  • Tadalafil OAD Efficacy in ED

  • Tadalafil OAD Safety and Tolerability in ED

  • Tadalafil OAD – Psychosocial Outcome and Partner Data


Tadalafil once a day why when for whom

ErectileDysfunction - Treatment algorithm

Lifestyle changes

andriskfactor

modification

Identifyandtreat

‘curable‘ causesof

ED

Hatzimouratidis K. et al.; EurUrol2010, 57: 804-814


Tadalafil once a day why when for whom

Link of ED andCardiovascularDisease

Study population: 9.457 men (age>55 years), 85% (8.063) without CVD atstudystart (7 yearsoffollow-up)

N= 4247 (number of men without ED at study start)

Thompson I.M.; JAMA 2005;294:2996-3002


Tadalafil once a day why when for whom

Link of ED andCardiovascularDisease

Time until cardiovascular event after initial report of ED (without any reports of ED or CV before)

Thompson I.M.; JAMA 2005;294:2996-3002

At risk, n = 2495; number of cardiovascular events, 255; 5-year estimate of cardiovascular events, 11%.


Tadalafil once a day why when for whom

Link of ED andCardiovascularDisease

Erectiledysfunctionis a strong predictorforseriouscardiovascularevents

Böhm M. et al.; Circulation 2010; 121:1439-1446


Tadalafil once a day why when for whom

ReductionofAdipositasMay ImproveED

  • 110 obesemen, 35 – 55 years, BMI 30-49 kg/m2 –

2 yearsintervention: Reductiondietandincreasedphysicalactivity

Weightloss: Intervention group – 15 kg Controlgroup – 2 kg

CG

IG

CG

IG

IG

CG

CG

IG

CG

IG

p=0,01

p=0,02

p=0,02

p=0,02

p=0,008

 Waist-to-hip ratio

 Glucose (mg/dl)

 IIEF-Score

 Blood pressure (mmHg)

 Platelet aggregation (%)

Endothelian function: Response to L-Arginin

CG: Control group (n=55) IG: Intervention group (n=55) ED defined as IIEF≤ 21

Esposito K et al.;JAMA 2004;291;2978-84


Tadalafil once a day why when for whom

PhysicalActivityand Maintenance ofErectileFunction

The risk of severe erectile dysfunction was decreased by 82.9% for males with physical activity of at least 3000 kcal/wk compared with males with physical activity under 3000 kcal/wk (OR = 0.171, p = 0.018)

PhysicalActivityCorrelateswith IIEF-5-Score

Kratzik C. et al; EurUrol; 2009; 55, 509-517


Physical activity and pde 5 inhibitors

PhysicalActivityand PDE-5-Inhibitors

Physicalactivitymaysupport PDE-5-Inhibitors in treatmentof ED

Mild ED

Normalised erections

n= 27

n= 30

physicalactivity

only

**p= 0.003

IIEF-EF: 24.7**

IIEF-EF: 26.7**

*p= 0.004

Maio G. et al.: J Sex Med. 2010;7(6):2201-8


Tadalafil once a day why when for whom

ErectileDysfunction - Treatment Algorithm

PDE-5Is arefirstlinetherapy1aA

Daily administrationof PDE5-Is mayimproveresultsandrestoreerectilefunction1bA

PDE-5Is arefirstlinetherapy1aA

Daily administrationof PDE5-Is mayimproveresultsandrestoreerectilefunction1bA

Longereffectivedaily

Shorter effectiveon demand

Longer effective(up to 36 h) on demand

Sildenafil 25 – 100 mg

Vardenafil 5 – 20 mg

Tadalafil 5mg

Tadalafil 10/20 mg

Hatzimouratidis K. et al.; EurUrol2010,57: 804-814


Tadalafil once a day why when for whom

Introduction –

Why the Once-Daily Option

  • Oral PDE5 inhibitors successfully treat ED1; however,

    • Ameliorating the full psychological impact of ED remains a challenge2

    • One complication is the lack of a clear pattern of timing of sexual activity for many couples2

  • Once-daily dosing would offer an alternative for couples who prefer spontaneous instead of scheduled sexual activities, or for those who anticipate frequent sexual activities

ED=erectile dysfunction; PDE5=phosphodiesterase 5

1. Eardley I et al. J Sex Med 2010;7:524-40.

2. Fisher W et al. J Sex Med 2005;2:675-84.


Tadalafil once a day why when for whom

Introduction –

Why the Once-Daily Option

  • Dosing paradigms that eliminate coordinating dosing with sexual activity are desirable to accommodate individual patterns and spontaneity of sexual intimacy1-3

  • Tadalafil is suited for use as a once-daily ED therapy, owing to its long half-life (17.5 hours)4

ED=erectile dysfunction; PDE5=phosphodiesterase 5

1. Carson C et al. BJU Int 2004;93:1276-81.

2. Rajfer J et al. Int J Impot Res 2007;19:95-103.

3. Dunn M et al. Int J Impot Res 2007;19:119-23.

4. Forgue S et al. Br J Clin Pharmacol 2006;61:280-8.


Tadalafil once a day why when for whom

Tadalafil Pharmacokinetics and Once-Daily Dosing

  • The mean half-life of tadalafil is 17.5 hours1,2

    • Steady-state plasma concentrations are attained within5 days of daily dosing

    • Exposure is approximately 1.6-fold greater than after a single dose3:

      • Daily tadalafil 10 mg  16 mg at steady state

      • Daily tadalafil 5 mg  8 mg at steady state

  • This duration of efficacy may permit men with ED and their partners to disconnect sexual activity from dosing

ED=erectile dysfunction

1. Cialis [US Package Insert] 2010.

2. Cialis [EU Summary of Product Characteristics] 2010.

3. Forgue S et al. Br J Clin Pharmacol 2006;61:280-8.


Tadalafil once a day why when for whom

Predicted Tadalafil

Concentration-Versus-Time Profiles

Tadalafil Plasma Concentrations Over 1 Week

400

350

Tadalafil 5 mg OAD

300

Tadalafil 20 mg single dose

250

200

Tadalafil Plasma Concentration (ng/mL)

150

100

50

0

0

24

48

72

96

120

144

168

Time (hours)

OAD=Once-a-Day or Once-Daily

Wrishko R et al. J Sex Med 2009;6:2039-48.


Contents

Contents

  • Modern management of erectile dysfunction

  • Why the Once-Daily/Once-a-day (OAD) Alternative toOn-Demand Dosing in Erectile Dysfunction (ED)

  • Tadalafil OAD Efficacy in ED

  • Tadalafil OAD Safety and Tolerability in ED

  • Tadalafil OAD – Psychosocial Outcome and Partner Data


Overview of once daily tadalafil clinical registration studies

Overview of Once-Daily Tadalafil Clinical (Registration) Studies

ED=erectile dysfunction; OAD=Once-Daily/Once-a-Day

3. Hatzichristou D et al. Diabet Med 2008;25:138-146.

1. Porst H et al. Eur Urol 2006;50:351-359.

2. Rajfer J et al. Int J Impot Res 2007;19:95-103.


Study 1 secondary endpoint percentage of men with no ed at 12 weeks iief ef 26

Study 1 Secondary Endpoint: Percentage of Men With “No ED” at 12 Weeks(IIEF EF ≥26)

Placebo

100

Tadalafil 5 mg OAD

90

Tadalafil 10 mg OAD

80

*p<0.001 vs placebo

70

*

52%

*

51%

60

% of Patients

50

40

30

20

8%

10

0

Tadalafil10 mg OAD

(n=101)

Tadalafil 5 mg OAD

(n=103)

Placebo

(n=48)

Patients with IIEF EF <26 at Baseline

IIEF EF=International Index of Erectile Function Erectile Function Domain

Porst H et al. EurUrol 2006;50:351-359.


Historical comparison iief ef domain pooled once daily and integrated on demand

Historical Comparison: IIEF EF DomainPooled Once-Daily and Integrated On-Demand

Placebo

Tadalafil 2.5 mg OAD

Tadalafil 5 mg OAD

Tadalafil 10 mg On-Demand

Tadalafil 20 mg On-Demand

*p<0.001 vs placebo

*23.2

*21.9

*21.1

*19.2

15.3

14.9

Mean IIEF EF Domain Score

Baseline

(n=147)

(n=93)

(n=203)

(n=638)

(n=321)

(n=1143)

Once-Daily1

(12-week data from a 12-2 and 24-week3 study)

On-Demand4

(11 pooled 12-week studies)

IIEF EF=International Index of Erectile Function Erectile Function Domain; OAD = Once-Daily/Once-a-Day

1. Donatucci et al. Curr Med Res Opin 2008; 24:3383-3392.

2. Porst H et al. Eur Urol 2006;50:351-359

3. Rajfer J et al. Int J Impot Res 2007;19:95-103.

4. Carson et al. BJU Int 2004;93:1276-1281.


Historical comparison sep3 pooled once daily and integrated on demand

Historical Comparison: SEP3Pooled Once-Daily and Integrated On-Demand

Placebo

Tadalafil 5 mg OAD

Tadalafil 2.5 mg OAD

Tadalafil 10 mg On-Demand

Tadalafil 20 mg On-Demand

*p<0.001 vs placebo

*68%

*62%

*58%

*50%

Mean Per-Patient % SEP3 “Yes”

31%

33%

Baseline

(n=144)

(n=92)

(n=201)

(n=638)

(n=321)

(n=1143)

Once-Daily1

(one 12-2 and one 24-week3 study)

On-Demand4

(11 pooled 12-week studies)

SEP3=Sexual Encounter Profile Question 3: “Did your erection last long enough to have successful intercourse?”

1. Donatucci et al. Curr Med Res Opin 2008; 24:3383-3392.

2. Porst H et al. EurUrol 2006;50:351-359

3. Rajfer J et al. Int J Impot Res 2007;19:95-103.

4. Carson et al. BJU Int 2004;93:1276-1281.


Once daily tadalafil longterm effectiveness

Once-Daily Tadalafil: Longterm Effectiveness


Once daily tadalafil open label extensions of oad studies general ed population

Once-Daily Tadalafil Open-Label Extensions of OAD Studies (General ED Population)

  • 1-year, open-label extension (once-daily tadalafil 5 mg)3following Study 1 (12-week double-blind, placebo-controlled of once-daily tadalafil 5 mg or 10 mg (N=234)1

  • 2-year, open-label extension (once-dailytadalafil 5 mg)3following Study 2 (24-week double-blind, placebo-controlled of once-daily tadalafil 2.5 mg or 5 mg (N=238)2

ED=erectile dysfunction; OAD=Once-Daily/Once-a-Day

  • Porst H et al. Eur Urol 2006;50:351-359.

  • Rajfer J et al. Int J Impot Res 2007;19:95-103.

3. Porst H et al. J Sex Med 2008;5:2160-2169.


Once daily tadalafil open label extension studies 1 and 2

Once-Daily Tadalafil:Open-Label Extension Studies 1 and 2

Treatment Free

Run-In Period

Study 1 Open-Label Extension*

*Extension primary endpoints: AEs, ECGs, labs

†PAIRS and GAQ only measured in Study 22

AE=adverse event; ECG=Electrocardiogram; GAQ=Global Assessment Question; IIEF=International Index of Erectile Function; PAIRS=Psychological and Interpersonal Relationship Scales; SEP=Sexual Encounter Profile

12-Week

Placebo-

Controlled

Tadalafil 5 mg OAD (N=234)

Study 11

Treatment Free

Week:

-4

0

12

Month:

4

8

12

13

IIEF

Labs

ECG

IIEF

Labs

ECG

IIEF

Labs

ECG

IIEF

Labs

ECG

Randomization

Treatment Free

Run-In Period

Study 2 Open-Label Extension*

24-Week

Placebo-

Controlled

Study 22

Tadalafil 5 mg OAD (N=238)

Week:

-4

0

24

Month:

3

6

9

12

15

18

21

24

IIEF

SEP

IIEF

GAQ†

Labs

ECG

IIEF

IIEF

GAQ†

Labs

ECG

IIEF

GAQ†

Labs

ECG

IIEF, SEP, PAIRS†

Every 4 Weeks

Every 3-4 Months: SEP and PAIRS

  • Porst H et al. Eur Urol 2006;50:351-359.

  • Rajfer J et al. Int J Impot Res 2007;19:95-103.

3. Porst H et al. J Sex Med 2008;5:2160-2169.


Once daily tadalafil 5 mg longterm effectiveness iief ef

Once-Daily Tadalafil 5 mg Longterm Effectiveness: IIEF EF

23

2-Year Extension

1-Year Extension

Mean IIEF EF Domain Score

229

229

217

213

205

204

170

153

139

Baseline

4-mos

8-mos

12-mos

Baseline

6-mos

12-mos

18-mos

24-mos

In the 1-year extension, patients were washed out for 1 month following the open-label extension

At the end of this washout period, the mean IIEF EF Domain score was 16.0

IIEF EF=International Index of Erectile Function Erectile Function Domain; mos = months’ study visit

Porst H et al. J Sex Med 2008;5(9):2160-2169.


Once daily tadalafil 5 mg longterm effectiveness percentage of men achieving iief ef 26

Once-Daily Tadalafil 5 mg Longterm Effectiveness: Percentage of Men Achieving IIEF EF ≥26

24

1-Year Extension Study

2-Year Extension Study

% of Patients with NormalIIEF EF Domain Score

N=202

N=135

Patients with IIEF EF <26 at Baseline

IIEF EF=International Index of Erectile Function Erectile Function Domain

Porst H et al. J Sex Med 2008;5(9):2160-2169.


Once daily tadalafil longterm effectiveness iief ef in 1 and 2 yr open label extensions

Once-Daily Tadalafil Longterm Effectiveness: IIEF EF in 1- and 2-yr Open-Label Extensions

1-Year Open-Label Extension

2-Year Open-Label Extension

30

24.8

24.1

25

20

14.0

15

Mean IIEF EF Domain Score

16.0

13.7

10

5

N=

N=

229

205

229

---

---

204

213

170

206

---

---

153

---

139

217

---

0

Baseline

4

8

12

16

20

24

Month of Open-Label Extension

IEF EF=International Index of Erectile Function Erectile Function Domain; N=number of evaluable patients

Porst H et al. J Sex Med 2008;5(9):2160-2169.


Oad longterm effectiveness conclusions

OAD Longterm Effectiveness: Conclusions

Efficacy improvements observed after 12 and 24 weeks in the placebo-controlled study periods1,2 were maintained as effectiveness improvements after 1 and 2 years ofopen-label treatment3

There was no evidence of tolerance or treatment resistance (tachyphylaxis) after up to 2 years of tadalafil 5 mgonce-daily dosing3

Longterm, once-daily tadalafil treatment provides a viable treatment alternative to on-demand dosing of tadalafil for men with ED3

26

ED=erectile dysfunction; OAD=once-daily/once-a-day

1. Porst H et al. Eur Urol 2006;50:351-359.

2. Rajfer J et al. Int J Impot Res 2007;19:95-103.

3. Porst H et al. J Sex Med 2008;5(9):2160-2169.


Tadalafil oad onset of efficacy 2 study 1 2 retrospective sub analysis 3 and prospective study 3

Tadalafil OAD Onset of Efficacy: 2-Study1,2 Retrospective Sub-Analysis3 and Prospective Study3

  • Porst H et al. EurUrol2006;50(2):351-359.

  • Rajfer J et al. Int J Impot Res 2007;19(1):95-103.

  • SeftelA et al. J Urol. 2011 ;185(1):243-8


Tadalafil once a day why when for whom

ErectileDysfunction - Treatment Algorithm

Hatzimouratidis K. et al.; EurUrol2010, 57 : 804-814


Tadalafil 5 mg oad onset of efficacy retrospective 2 trial 1 2 subanalysis 3

Tadalafil 5 mg OAD Onset of Efficacy: Retrospective 2-Trial1,2 Subanalysis3

Successful IntercourseDuring First 10 Days of Therapy3

100

80

*

*

*

*

*

*

*

*

*

60

Tadalafil 5 mg OAD

% Patients w/Successful Attempt

Placebo

40

20

0

10

6

4

2

8

Day of Therapy

*p<0.05 by Chi-square test.

Plot is percentage of patients having successful intercourse by Day 1, by Day 2, etc.

1. Porst H et al. Eur Urol 2006;50:351-359.

2. Rajfer J et al. Int J Impot Res 2007;19:95-103.

3. Seftel A et al. J Urol. 2011 ;185(1):243-8

.


Tadalafil once a day why when for whom

Tadalafil 2.5 mg and 5 mg OAD Onset of Efficacy Prospective Study: Percentage Successful Attempts by SEP3 (Secondary Analysis)

Cumulative Percentage of Successful Intercourse Attempts by SEP3During 14-Day Double-Blind Period

50

*

*

45

*

*

Tadalafil 5 mg OAD

40

*

*

Tadalafil 2.5 mg OAD

35

Placebo

30

% of Successful Attempts

25

20

15

*p<0.025 tadalafil 5 mg OAD versus placebo (Day 2 to Day 14)

†p<0.025 tadalafil 2.5 mg OAD versus placebo (Day 3 to Day 14)

10

5

0

Baseline

7

11

2

3

4

Day 1

14

SEP3=Sexual Encounter Profile Question 3: “Did your erection last long enough to have successful intercourse?”

Seftel A et al. J Urol. 2011 ;185(1):243-8


Tadalafil 5 mg oad onset of efficacy conclusions

Tadalafil 5 mg OAD Onset of Efficacy: Conclusions

Onset of efficacy of once-daily tadalafil 2.5 mg or 5 mg within a few days (Day 2 or Day 3) of initiating therapy was demonstrated by the following:

A 2-study (general ED population)1,2 retrospective analysis3

A prospective trial (N=372)3comprised of a 2-week double-blind placebo-controlled period with instructions for multiple attempts followed by a 2-week open-label period (tadalafil 5 mg only;no attempt requirements)

ED=erectile dysfunction

1. Porst H et al. Eur Urol 2006;50:351-359.

2. Rajfer J et al. Int J Impot Res 2007;19:95-103.

3. Seftel A et al. J Urol. 2011 ;185(1):243-8.


Tadalafil oad reliability of efficacy 2 study 1 2 retrospective analysis 3

Tadalafil OAD Reliability of Efficacy: 2-Study1,2 Retrospective Analysis3

1. Porst H et al. Eur Urol 2006;50(2):351-359.

2. Rajfer J et al. Int J Impot Res 2007;19(1):95-103.

3. Shabsigh R et al. Int J Impot Res 2010;22(1):1-8.


Tadalafil oad reliability of efficacy

Tadalafil OAD: Reliability of Efficacy

  • A pooled retrospective analysis of the two general ED OAD registration studies1,2 for the initial 12 weeks of either study examined first-attempt success rate and the reliability of response* in men treated with tadalafil 2.5 mg OAD (n=96) or 5 mg OAD (n=206) versus placebo (n=148)3

  • Cumulative proportion of men with intercourse success (“Yes” to SEP3) at any time (to Week 12) by number of attempts was also calculated

*Defined as rate of intercourse success (following successful attempt) per Sexual Encounter Profile Question 3 (SEP3):

“Did your erection last long enough for you to have successful intercourse?” after a successful attempt

ED=erectile dysfunction; OAD=Once-a-Day or Once-Daily

1. Porst H et al. Eur Urol 2006;50(2):351-359.

2. Rajfer J et al. Int J Impot Res 2007;19(1):95-103.

3. Shabsigh R et al. Int J Impot Res 2010;22(1):1-8.


Once daily tadalafil 2 study 1 2 retrospective analysis 3 success sep3 by number of attempts

Once-Daily Tadalafil: 2-Study1,2 Retrospective Analysis3 Success (SEP3) By Number of Attempts

Cumulative Proportion of Patients With Intercourse Success (“Yes” to SEP3) by Number of Attempts During the Initial 12-Weeks of 2 Studies1,2

90

Tadalafil 5 mg OAD

80

Tadalafil 2.5 mg OAD

70

Placebo

60

% Who Recorded Successful Intercourse

50

40

30

20

10

0

0

2

4

6

8

10

12

Number of Intercourse Attempts

SEP3=Sexual Encounter Profile Question 3: “Did your erection last long enough to have successful intercourse?”

1. Porst H et al. Eur Urol 2006;50(2):351-359.

2. Rajfer J et al. Int J Impot Res 2007;19(1):95-103.

3. Shabsigh R et al. Int J Impot Res 2010;22(1):1-8.


Tadalafil 5 mg oad reliability of efficacy conclusions

Tadalafil 5 mg OAD Reliability of Efficacy: Conclusions

Reliability of efficacy of tadalafil OAD over 12 weeks ─“rate of intercourse success (SEP3) after successful attempt”─ by a 2-study1,2 retrospective analysis3 (2.5 mg or 5 mg doses only) revealed the following:

Following initial success, a greater proportion of men (85.9%; p<0.001) taking tadalafil 5 mg had subsequent success compared to placebo (70.2%)

Men who may not be initially successful under treatment with once-daily tadalafil for ED may have increased success on subsequent intercourse attempts (up to 10 attempts)3

SEP3=Sexual Encounter Profile Question 3: “Did your erection last long enough to have successful intercourse?”

1. Porst H et al. Eur Urol 2006;50(2):351-359.

2. Rajfer J et al. Int J Impot Res 2007;19(1):95-103.

3. Shabsigh R et al. Int J Impot Res 2010;22(1):1-8.


Tadalafil once daily efficacy summary

Tadalafil Once-Daily Efficacy Summary

  • Once-daily tadalafil improved erectile function by IIEF EF domain in general ED placebo-controlled studies (2.5 mg or 5 mg)1,2as well as in 1- and 2-year open-label studies (5-mg only)3

  • Onset of efficacy of tadalafil 2.5 mg or 5 mg OAD within a few days (Day 2 or Day 3) of initiating therapy has been demonstrated1-2,4

  • Reliability: Over 12 weeks and post initial success, more men on tadalafil 5 mg OAD (85.9%; p<0.001) had subsequent success than placebo (70.2%)5

ED=erectile dysfunction; IIEF EF=International Index of Erectile Function Erectile Function Domain;

OAD=Once-a-Day or Once-Daily

1. Porst H et al. EurUrol2006;50(2):351-359.

2. Rajfer J et al. Int J Impot Res 2007;19(1):95-103.

3. Porst H et al. J Sex Med 2008;5(9):2160-2169.

4. Seftel A et al. J Urol. 2011 ;185(1):243-8

5. Shabsigh R et al. Int J Impot Res 2010;22(1):1-8.


Contents1

Contents

Modern management of erectile dysfunction

Why the Once-Daily/ Once-a-Day (OAD) Alternative to On-Demand Dosing in Erectile Dysfunction (ED)

Tadalafil OAD Efficacy in ED

Tadalafil OAD Safety and Tolerability in ED

Tadalafil OAD – Psychosocial Outcome and Partner Data


Historical comparison adverse events once daily studies 1 and 2 vs on demand randomized trials

Historical Comparison: Adverse Events – Once-Daily (Studies 1 and 2) vs. On-Demand Randomized Trials

*All once-daily and on-demand trials were randomized and placebo-controlled

AE=Adverse Event; OAD=Once-A-Day; TEAE=Treatment-Emergent Adverse Events

1. Porst H et al. Eur Urol 2006;50:351-9.

2. Rajfer J et al. Int J Impot Res 2007;19:95-103.

3. Donatucci et al. Curr Med Res Opin 2008; 24:3383-92.

4. Carson CC et al. BJU Int2004;93:1276-81.


Long term safety most common adverse events at 12 months extension studies 1 and 2

Long-Term Safety: Most Common Adverse Events at 12 Months (Extension Studies 1 and 2)

AE=Adverse Event; OAD=Once-A-Day; OL=Open-Label; Treatment-Emergent Adverse Events

1. Porst H et al. J Sex Med 2008;5:2160–9.

2. Rajfer J et al. Int J Impot Res 2007;19:95-103.


Cardiovascular safety tadalafil once daily dosing 3x weekly dosing all studies combined

Cardiovascular Safety: Tadalafil Once-Daily Dosing, 3x/Weekly Dosing, All Studies Combined

*Framingham study: MI incidence rates of 0.61/100 PYs (45-54 y) and 2.25/100 PYs (75-84 y)

†Combined studies – sample sizes not additive: some received tadalafil in placebo-controlled as well as open-label trials

‡One patient who had a MI had been randomized to tadalafil, but had not taken drug

CVTEAE=Cardiovascular Treatment-Emergent Adverse Event; CI=Confidence Interval; MI=Myocardial Infarction

Kloner R et al. Am J Cardiol 2006;97:1778-84.


Tadalafil once daily safety and tolerability summary

Tadalafil Once-Daily Safety and Tolerability Summary

  • Most patients completed open-label extensions of the two once-daily studies in the general erectile dysfunction population (208/234 [1-year extension]; 139/238 [2-year extension])

  • Incidence and type of adverse events was similar for tadalafil once-daily 5 mg (24 months) and on-demand 5/10/20 mg (24 months)

  • No events suggestive of drug-related toxicity on tests of visual function were evident with 6 months’ daily treatment

  • Incidence of cardiovascular adverse events was low, and comparable for tadalafil- and placebo-treated patients


Contents2

Contents

  • Modern management of erectile dysfunction

  • Why the Once-Daily / Once-a-Day (OAD) Alternative to On-Demand Dosing in Erectile Dysfunction (ED)

  • Tadalafil OAD Efficacy in ED

  • Tadalafil OAD Safety and Tolerability in ED

  • Tadalafil OAD – Psychosocial Outcome and Partner Data


Once daily tadalafil for ed partner and psychosocial outcome data introduction

Once-Daily Tadalafil for ED: Partner and Psychosocial Outcome Data Introduction

  • Erectile dysfunction (ED) is a condition that can affect more than male erectile functioning; it also has an impact on patient and partner sexual quality of life (SQoL) and other psychosocial outcomes1,2

  • Biopsychosocial considerations that include the partner and the relationship are important in the treatment of ED3-5

1. Althof SE Int J Impot Res 2002;14 Suppl 1:S99-S104.

2. Althof SE. Urology 2002;59(6):803-10.

3. McCabe M et al. J Sex Med 2010;7(1 Pt 2):327-36

4. Hackett G et al. J Sex Med 2008;5(8):1841-65.

5. Fisher WA et al. J Sex Med 2009;6(10):2746-60.


Tadalafil once a day why when for whom

Tadalafil Once Daily and Sexual Quality of Life in Patient and Partner


Tadalafil once a day why when for whom

Tadalafil 5 mg OAD: Patient and Partner Scores on the SLQQ–SQoL Items 1-5

100

*p<0.001 change from baseline vs placebo

Placebo

Partners of Placebo-Treated

Baseline

Tadalafil 5 mg OAD

Partners of TAD 5 mg OAD-Treated

80

*

*

*

*

*

*

Better

*

*

*

*

60

Same as prior to ED

(range 0–100)

Mean Per Item SLQQ-SQoL Score

40

20

Worse

0

Item 1

Item 2

Item 3

Item 4

Item 5

Freq

of Sex

Duration

of Sex

Ease of Insertion

Ease of Orgasm

Ease Initiating

Female Partners

SLQQ-SQoL Individual Items (1→ 5)

ED Patients

SLQQ-SQoL Individual Items (1→ 5)

Item 1

Item 2

Item 3

Item 4

Item 5

Freq

of Sex

Duration

of Sex

Ease of Insertion

Ease of Orgasm

Ease Initiating

Freq=Frequency; SLQQ=Sexual Life Quality Questionnaire; SQoL=Sexual Quality of Life; TAD=tadalafil

Rubio-Aurioles et al. J Sex Med 2009;6(5):1314-23.


Tadalafil once a day why when for whom

Tadalafil 5 mg OAD: Patient and Partner Scores on the SLQQ–SQoL Items 6-10

100

*p<0.001 change from baseline vs placebo

Placebo

Partners of Placebo-Treated

Baseline

Tadalafil 5 mg OAD

Partners of TAD 5 mg OAD-Treated

80

*

*

*

*

*

*

*

*

*

*

Better

60

Same as prior to ED

Mean Per Item SLQQ-SQoL Score

40

( range 0–100 )

20

Worse

0

Item 6

Item 7

Item 8

Item 9

Item 10

Item 6

Item 7

Item 8

Item 9

Item 10

Carefree Feelings

Pleasure of Anticipation

Carefree Feelings

Pleasure Orgasm

Pleasure Overall

Partner Pleasure

Pleasure of Anticipation

Pleasure Orgasm

Pleasure Overall

Partner Pleasure

Female Partners

SLQQ-SQoL Individual Items (6→ 10)

ED Patients

SLQQ-SQoL Individual Items (6→ 10)

SLQQ=Sexual Life Quality Questionnaire; SQoL=Sexual Quality of Life; TAD=tadalafil

Rubio-Aurioles et al. J Sex Med 2009;6(5):1314-23.


Tadalafil once a day why when for whom

Once-Daily Tadalafil 5 mg and Treatment Satisfaction (Secondary Endpoint)

*p<0.001 vs placebo

Placebo

Partners of Placebo-Treated

100

Tadalafil 5 mg OAD

Partners of TAD 5 mg OAD-Treated

80

75*

73*

60

55

51

Mean SLQQ-THX Domain Score(6 items; range 0 – 100)

40

20

0

(n=238)

(n=72)

(n=244)

(n=70)

ED Patients

Female Partners

SLQQ-THX

SLQQ=Sexual Life Quality Questionnaire; TAD=tadalafil; –THX=Treatment Satisfaction Domain

Seftel AD et al. Int J Impot Res 2009;21(4):240-8.


Once daily tadalafil 5 mg and psychosocial outcomes by sear scale secondary endpoints

Once-Daily Tadalafil 5 mg and Psychosocial Outcomes by SEAR Scale (Secondary Endpoints)

*p<0.001 change from baseline vs placebo

Placebo

Tadalafil 5 mg OAD

Baseline

100

81*

80*

79*

80

73*

† SEAR score

change from baseline was minus 0.7 points

58†

60

65

54

52

59

Mean SEAR Score

55

43

51

50

46

40

39

38

20

0

n=

72

72

72

244

244

244

244

72

Sexual Relationship

Domain

Confidence

Domain

Self–Esteem SS

Overall Relationship SS

ED Patients

OAD=Once-Daily/Once-a-Day; SEAR=Self-Esteem and Relationship Questionnaire; SS=Subscale

Seftel AD et al. Int J Impot Res 2009;21:240-8.


Tadalafil once a day why when for whom

Tadalafil Once-a-day:

Why, When, for Whom?

  • Modern management of erectile dysfunction

    • Careful assessment (silent CAD!), modify risk-factors, PDE5-I’s first-line treatment, involve partner

  • Why the Once-Daily/Once-a-day (OAD) Alternative to On-Demand Dosing in Erectile Dysfunction (ED)

    • Daily dosing has been included into EAU-Guidelines – offer this treatment-option to your patients

  • Tadalafil OAD Efficacy in ED

    • Tadalafil OAD shows comparable efficacy as on-demand treatment-options (IIEF, SEP)


Tadalafil once a day why when for whom

Tadalafil Once-a-day:

Why, When, for Whom?

  • Tadalafil OAD Safety and Tolerability in ED

    • Less adverse events (historically) compared with on-demand therapy-regimens

  • Tadalafil OAD – Psychosocial Outcome and Partner Data

    • Majority of patients’ and partners’ sexual quality of life improves to scores comparable to those in couples without ED


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