1. CLINICAL TRIAL ON
ERECTILE DYSFUNCTION
case study
K.UPENDRA REDDY
2010H146037H

2. OFFICIAL TITLE
Tadalafil 5 mg Once a Day Compared to Placebo
in Improving Erectile Dysfunction and Sexual
Quality of Life

3. Sponsor Eli Lilly and Company
collaborator ICOS corporation
information provided by Eli Lilly and Company
ClinicalTrials.gov Identifier NCT00422734
STUDY LOCATIONS:
 United States, Austria ,France,
Germany,Mexico

4. PURPOSE
 To evaluate the effect of tadalafil on sexual
quality of life
 To evaluate the effect of tadalafil on Erectile
Dysfunction
condition intervention phase
Impotency Drug: placebo
Drug:
Tadalafil
Phase III

5. Study Type: Interventional
Study Design:
 Allocation: Randomized.
 Control: Placebo Control.
 Endpoint Classification: Safety/Efficacy Study.
 Intervention Model: Parallel Assignment.
 Masking: Double Blind (Subject, Investigator).
 Primary Purpose: Treatment.

6. Eligibility
 Ages Eligible for Study: 18 Years and older.
 Genders Eligible for Study: Male.
 Accepts Healthy Volunteers: No.
Inclusion criteria:
 History of erectile dysfunction (ED) for at least 3 months
duration
 Anticipate to have the same female partner willing to
participate throughout the study
 At least 18 years of age at Visit 1 and agree to make at least 4
sexual attempts during the early phase of the study
 Adequate partner sexual function as determined by a Female
Sexual Function Index
 Willing to record responses to efficacy questionnaires, sexual
quality of life questionnaires and other instruments used in the

7. Exclusion criteria:
 May not participate in the study if you taken tadalafil
previously.
 History of cardiac conditions including angina requiring
treatment with nitrates, heart disease of coronary conditions
including myocardial infarction, bypass surgery, angioplasty
or stent placement for specified time before starting the study.
 With a sexual partner not willing to complete the scales.
 Use of nitrates.

8. OUTCOME MEASURES
Primary outcome measures:
Change From Baseline to Endpoint in the
International Index of Erectile Function (IIEF)-
Erectile Function Domain Score
Improvement in the Sexual Quality of Life in the
Subject and His Study Partner as Measured by
the Sexual Quality of Life (SQoL) Domain of the
Sexual Life Quality Questionnaire (SLQQ)
Change From Baseline to Endpoint in the
Percent of "Yes" Responses to Sexual Encounter
Profile (SEP) Diary Questions 2 (SEP2) and 3

9. Secondary outcome measures
Intercourse Satisfaction Domain - Subject
Response.
Female Sexual Function Index (FSFI) - Partner
Response.
Overall Satisfaction Domain of the International
Index of Erectile Function (IIEF-OS) - Subject
Response.
Sexual Encounter Profile (SEP) Questions 1 - 5
–Subject & Partner Response.

10. RECRUITEMENT INFORMATION
Recruitment Status completed
Enrollment 342
Start date November 2006
Primary Completion
Date
January 2008
Completion Date January 2008

11. ARMS ASSIGNED
INTERVENTIONS
1: Placebo Comparator Drug: Placebo
placebo tablet taken
orally once a day for 12
weeks
2: Active Comparator Drug: tadalafil
5 mg tadalafil tablet taken
orally once a day for 12
weeks

12. PARTICIPANT FLOW
Placebo Tadalafil
Started 78 264
Completed 64 243
Not completed
Physician decision
Protocol violation
Withdrawal by subjects
Adverse events
Partner decision
14
1
1
12
0
0
21
1
6
8
3
3

13. BASELINE CHARACTERISTICS
Placebo Tadalafil Total
No of participants 78 264 342
Age 53.82 ± 10.72 54.42 ± 10.04 54.29 ± 10.18
ED duration
>= 1 year
3 to 6 months
6 months to 1 yr
73
1
4
24
8
16
313
9
20
ED severity
Mild (17-30)
Moderate (11-16)
Severe (1-10)
Missing
35
22
20
1
123
71
63
7
158
93
83
8
IIEF domain score
[units: units on a scale]
Mean ± Standard
Deviation
15.27 ± 6.49 15.73 ± 6.13 15.62 ± 6.21

14. OUTCOME MEASURES
 Primary outcomes
1. Change From Baseline to Endpoint in the
International Index of Erectile Function (IIEF)-
Erectile Function Domain Score (Sum of IIEF
Questions 1-5 and 15) [ Time Frame: Baseline
and 12 weeks ]Placebo Tadalafil
Participants Analyzed 72 244
Change in Erectile
Function Domain Score
[units: units on a scale]
Least Squares Mean
± Standard Error
0.49 ± 0.781 8.03 ± 0.449

15. 2. Improvement in the Sexual Quality of Life in the
Subject and His Study Partner as Measured by
the Sexual Quality of Life (SQoL) Domain of the
Sexual Life Quality Questionnaire (SLQQ) [
Time Frame: Baseline and 12 weeks ]
Placebo Tadalafil
Participants
Analyzed
72 244
Improvement in the
Sexual Quality of
Life
[units: units on a scal
e]
Least Squares Mean
± Standard Error
SQoL - Subject
12.59 ± 2.866
7.93 ± 2.861
39.37 ± 1.651
32.87 ± 1.638

16. 3. Change From Baseline to Endpoint in the
Percent of "Yes" Responses to Sexual
Encounter Profile (SEP) Diary Questions 2
(SEP2) and 3 (SEP3). [ Time Frame: Baseline
and 12 weeks ]
Placebo Tadalafil
Participants Analyzed
Change in the
Percent of "Yes"
Responses to Sexual
Encounter Profile
(SEP)
Question 2
Question 3
2.19 ± 2.833
10.80 ± 3.767
28.80 ± 1.644
46.46 ± 2.185

17. Secondary outcome measures
1. Change From Baseline to Week 12 Endpoint
in the International Index of Erectile Function -
Intercourse Satisfaction Domain - Subject
Response [ Time Frame: Baseline and 12
weeks ]
Placebo Tadalafil
Participants
Analyzed
72 244
Change in
Intercourse
Satisfaction
Domain
0.09 ± 0.356 2.74 ± 0.205

18. 2. Change From Baseline to 12 Week Endpoint in
Overall Satisfaction Domain of the International
Index of Erectile Function (IIEF-OS) - Subject
Response [ Time Frame: Baseline and 12
weeks ]
Placebo Tadalafil
Participants
Analyzed
72 244
Change in
Overall
Satisfaction
Domain
0.44 ± 0.257 2.57 ± 0.148

19. Statistical Analysis to measure outcomes
Groups All groups
Method ANCOVA
P-value <0.001
Significance level 0.025

20. Serious adverse events
Placebo Tadalafil
Total, Adverse events
# participants affected
1 3
Pancreatitis 1/78 0/264
Hypersensitivity 0/78 1/264
Gastroenteritis 0/78 1/264
Cerebrovascular
accident
0/78 1/264

21. Other adverse events
Event Placebo Tadalafil
Headache 4 26
Dyspepsia 0 13
Nasal congestion 0 9
Diarrhoea 1 5
Painful erection 0 5
Pharyngitis 1 4
Nausea 0 3

22. Questionnaire
The International Index of Erectile Function
Questionnaire (IIEF)
1.Over the last month, how often were you
able to get an erection during sexual
activity?
 0 No sexual activity
 5 Almost always or always
 4 Most times (much more than half the time)
 3 Sometimes (about half the time)
 2 A few times (much less than half the time)

23. 2. Over the last month, when you had erections
with sexual stimulation, how often were your
erections hard enough for penetration?
3. Over the last month, when you attempted
intercourse, how often were you able to
penetrate your partner?
4. Over the last month, during sexual intercourse,
how often were you able to maintain your
erection after you had penetrated your partner?
5. Over the last month, during sexual intercourse,
how difficult was it to maintain your erection to
completion of intercourse?

24. 6. Over the last month, how many times have
you attempted sexual intercourse?
7. Over the last month, when you attempted
sexual intercourse how often was it
satisfactory for you?
8. Over the last month, how much have you
enjoyed sexual intercourse?
9. Over the last month, when you had sexual
stimulation or intercourse, how often did you
ejaculate?
10. Over the last month, when you had sexual
stimulation or intercourse, how often did you
have the feeling of orgasm (with or without
ejaculation)?

25. 11. Over the last month, how often have you
felt sexual desire?
12. Over the last month, how would you rate
your level of sexual desire?
13. Over the last month, how satisfied have
you been with your overall sex life?
14. Over the last month, how satisfied have
you been with your sexual relationship with
your partner?
15. Over the last month, how do you rate your
confidence that you can get and keep your
erection?

26. Area Question
s
Score
Range
Maximum
Score
Your
Score
Erectile
function
1-5, 15 0-5 30
Orgasmic
funtion
9, 10 0-5 10
Sexual
desire
11-12 1-5 10
Intercours
e
satisfactio
n
6-8 0-5 15
Overall
satisfactio
13-14 1-5 10

27. CONCLUSION:
Integrated analysis of data from phase III
trial demonstrated that tadalafil at dose 5 mg
significantly improved erectile function (vs
placebo) by all efficacy measures.
Improved quality of life
Tadalafil was safe and well tolerated in the
phase III studies, with headache and
dyspepsia being the most frequent adverse
events

28. REFERENCES:
 http://clinicaltrials.gov/ct2/show/results/NCT
00422734?term=erectile+dysfunction&sect=
X0125#all
 http://www.seekwellness.com/mensexuality/
questionnaire.htm
 http://en.wikipedia.org/wiki/Impotence
 http://www.healthcentral.com/erectile-
dysfunction/understanding-erectile-
dysfunction-44026-47.html

29. THANK YOU
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