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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 arefirstlinetherapy 1a A

Daily administrationof PDE5-Is mayimproveresultsandrestoreerectilefunction 1b A

PDE-5Is arefirstlinetherapy1a A

Daily administrationof PDE5-Is mayimproveresultsandrestoreerectilefunction1b A

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 Domain ED” at 12 WeeksPooled 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: SEP3 ED” at 12 WeeksPooled 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: ED” at 12 WeeksLongterm 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: (General ED Population)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 (General ED Population)

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 and 2-yr Open-Label Extensions

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: and 2-yr Open-Label Extensions 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

Erectile and 2-yr Open-Label ExtensionsDysfunction - 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-Trial and 2-yr Open-Label Extensions1,2 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 Study: Percentage Successful Attempts by SEP3 (Secondary Analysis)

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: Study: Percentage Successful Attempts by SEP3 (Secondary Analysis) 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 Study: Percentage Successful Attempts by SEP3 (Secondary Analysis)

  • 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-Study Study: Percentage Successful Attempts by SEP3 (Secondary Analysis)1,2 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 Study: Percentage Successful Attempts by SEP3 (Secondary Analysis)

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 Study: Percentage Successful Attempts by SEP3 (Secondary Analysis)

  • 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 Study: Percentage Successful Attempts by SEP3 (Secondary Analysis)

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 3x/Weekly Dosing, All Studies Combined

  • 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 3x/Weekly Dosing, All Studies Combined

  • 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 Outcome Data Introduction 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 Scale (Secondary Endpoints) 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 Scale (Secondary Endpoints) 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