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A
CLINICALSTUDY REPORTVIGRX PLUS
In Male Sexual
HealthPROTOCOL ID: VL/080305/DM

SPONSOR

Leading Edge Marketing
PO Box CR-56766, Suite 1210
Nassau Bahamas

Sponsor’s
Contact Person

Mr. Doug MacKay
DM Contact Management Ltd.

Tel: (250) 383-8267 extension 447
Fax: (250) 383-0896
CRO

Vedic Lifesciences Pvt. Ltd.
118, Morya House, Off. New Link
Road, Andheri (West),
Mumbai – 400053.
India.
Tel: 022-42025700

DATE: 08/05/2010

CONFIDENTIAL

INFORMATIONThis document is the property of Leading Edge Marketing and is confidential. Therefore, it may
not be photocopied, either in part or in full, or shown to any person not directly associated eitherwith the trial, or with the concerned ethics committee, or with the concerned regulatory authority.

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SYNOPSIS
Name of sponsor company : Leading Edge Marketing
Name of finished product : VigRX Plus capsules
Name of active ingredients:
Panax ginseng (Korean Red Ginseng)
Serenoa repens (Saw Palmetto)
Crataegus rivularis ( Hawthorne)
Ginkgo biloba
Turnera diffusa (Damiana)
Tribulus terrestris
Erythroxylum catuaba
Ptychopetalum olacoides (Muira Puama)
Cuscuta chinensis
Epimedium sagittatum
Bioperine (extract from Piper nigrum fruit )Title of the study: A triple blind, placebo controlled, randomized study to evaluate thesafety and efficacy of VigRX Plus capsules as a dietary supplement to improve erectile
function and maintain Male Sexual Health.
Investigators and study centres:1)Dr. Gaurang Shah
Jivdaya Hospital,Dharmoday bldg, Jivdaya
Mumbai86.INDIA.Mob: 9821019432.

lane, L.B.S. Marg,

Ghatkopar(W),2)Dr. R. K. Shimpi
Dept. of Urology,Noble Hospital, 153,Magarpatta City Road, Hadapsar,Pune-411 013.
INDIA.Mob : 9822059799
3)Dr. Suresh Patankar
Institute of urology,Survey no. 32/2A, Erandwane, Behind Mehendale garage,Gulwani
Maharaj road, Pune-4.INDIA.Mob : 9881256992
4)Dr. Manoj Chaudhari169, Parvati gaon, Bhaghirathi Medical Foundation, Pune – 400009, Phone. 9225571450
5)Dr. Vilas SabaleFirst floor, Vithal Acrade, Near Rupee bank, Pune Nasik Highway,Bhosari, Pune-411039
Mobile: 9822004630
Study period:
Date of first enrollment: 07/05/2009
Date of last completed: 17/12/2009

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Phase of study : Therapeutic exploratory
Objectives
Primary objective
To evaluate the efficacy of VigRX Plus capsules as a dietary supplement to improve
erectile function as assessed by Erectile function subscale of IIEF Questionnaire (IIEF-A)
from baseline to end of treatment as compared to placebo.
Secondary objectives• To evaluate the efficacy of VigRX Plus capsules as a dietary supplement for Male Sexual
Health as assessed by IIEF (Total)(International Index of Erectile Function)questionnaire from baseline to end of treatment as compared to placebo• To evaluate the efficacy of VigRX Plus capsules as a dietary supplement for Male Sexual
Health as assessed by IIEF-B questionnaire (sum of all the subscales of IIEF except
erectile function subscale) from baseline to end of treatment as compared to placebo• To evaluate the impact of VigRX Plus capsules as a dietary supplement for Male Sexual
Health as assessed by EDITS questionnaire (Patient & Partner version) as compared toplacebo• To evaluate the safety of VigRX Plus capsules as a dietary supplement for Male Sexual
Health from baseline to end of treatment as compared to placebo• To assess the effect of VigRX Plus on the sperm count, motility, semen volume frombaseline to end of treatment.
• To assess the effect of VigRX Plus on Serum testosterone from baseline to end oftreatment as compared to placebo

Diagnosis and main criteria for inclusion
1. Male subjects aged between 25-50 years
2. Subject having a monogamous, heterosexual relationship
3. Male subjects with IIEF-A score 11 to 23 & IIEF-B score 21 to 35 at screening visit &baseline visit
4. Subject provides written informed consent and comes for regular follow up

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Methodology
75 males between 25-50 years of age were recruited to get 60 completed cases. Subjects
with an IIEF erectile function domain score of 11-23 and remaining domains score of 2135 were eligible for the study. For each subject the study terminated after a maximal periodof 84 days from enrollment and included 5 follow up visits. After consenting to participate
subjects were put on 15 days wash-out period before being administered theinvestigational product or placebo. On baseline visit (Day 1), medical history and physicalexamination were performed, IIEF Total questionnaire was assessed and the trial
medications were dispensed. At all the follow-up visits (at an interval of 28 days) eachsubject was administered a new IIEF (Total) and an EDITS questionnaire. Each subject
received another supply of the trial medications during these visits. On Day 28 and Day
84 EDITS questionnaire partner version scores were obtained from partners who
consented for the same. Additionally at these visits subjects rated the tolerability of thetreatment they received. At the end of treatment investigator’s global assessment oftherapy and subject’s opinion on continuing with the trial medication was obtained.

Number of patients planned: 60 completed cases
Number of patients analysed :75
Test product, dose and mode of administration, batch number
VigRX Plus -2 capsules (each containing 360 mg of active composition) twice a day withmeals for 12 weeks, Batch No: VP01.
Reference therapy: Placebo 2 capsules twice a day with meals for 12 weeks
Batch No: VX01,

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Criteria for evaluation:
Primary efficacy evaluation
Improvement in IIEF-A (Erectile function domain of the International Index of Erectile
Function) score for erectile function domain as compared to placebo
Secondary efficacy evaluation:• Increase in total score of quality of sexual life questionnaire-IIEF (Total) as comparedto placebo

Secondary efficacy evaluation (continued)••••

Improvement in IIEF-B (other than the erectile function domain) score as comparedto placebo
Satisfaction with treatment (EDITS Patient & partner version) as compared toplacebo
Improvement in Semen Analysis Parameters as compared to placebo
Improvement in Serum Testosterone (Total) levels , as compared to placebo Safety

Monitoring of adverse events. Clinical examination, Assessment of vitals and laboratory
parameters.

Statistical methods
Analysis for safety was done on an intention-to treat population. This included subjects
who received at least one dose of treatment post randomization and for whom at least
one post baseline measurement was available. Missing data were imputed using last
observation carried forward (LOCF) method.
Analysis of efficacy was primarily done on a per protocol data set constituting of subjects
completing all the protocol required visits. Changes from baseline in IIEF scores wereassessed using analysis of covariance (ANCOVA). Data on EDITS (patient and partner
versions) were analysed by independent sample t test. Chi-square test was used toanalyse investigators’ assessment and subjects opinion across the two groups. All
statistical tests were applied at 5% level of significance.

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Results
Efficacy
Treatment with VigRX Plus resulted in a statistically significant increase (p<0.0001) of
IIEF-A, IIEF-B and IIEF-Total scores as compared to placebo, on Day 84 (end oftreatment).In subjects treated with VigRX Plus, mean increases from baseline to end oftreatment for IIEF-A, IIEF-B and IIEF-Total were 9, 20.1 and 11.56 respectively. The
corresponding increases in the placebo group were 0.62, 1 and 0.68.Treatment
satisfaction as assessed by EDITS (patient version) was statistically significantly higher
in the VigRX Plus group as compared to placebo on Day 28, Day 56 and Day 84. At theend of treatment, mean EDITS score was 82.31 in the VigRX Plus group and 36.78 in theplacebo group.

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Results (continued)
Female partners reciprocated the satisfaction levels experienced by their malecounterparts treated with VigRX Plus, with the mean EDITS (partner version) score of
69.58 in the VigRX Plus group being statistically greater than that of 25.5 in the placebogroup.
There was no statistically significant difference in the sperm count, semen volume andsperm motility between the two treatment groups. Serum Testosterone levels did notchange significantly in any of the study groups.
At the end of study, global assessment of therapy by investigator clearly saw asuperiority of outcomes in subjects receiving VigRX Plus as compared to those receiving
placebo, with statistical significance. Subjects’ opinion was also statistically significant infavour of VigRX Plus.
SafetyVigRX Plus and placebo both were safe and well tolerated in the study. Changes inlaboratory and vital signs were clinically insignificant. The only serious adverse event
reported in this study was when one subject from the VigRX Plus group suffered from
infection due to malarial parasite and was subsequently withdrawn from the study.
Conclusion
In conclusion, use of VigRX Plus for twelve weeks was significantly better than placebo
in improving erectile function in subjects with sexual dysfunction. It was also significantly
superior to placebo in improving the other aspects of sexual health such as libido,intercourse satisfaction, orgasmic function and overall satisfaction. The enhancement ofsexual function was endorsed by female partners of subjects receiving VigRX Plus.
VigRX Plus was safe and well tolerated in subjects with male sexual dysfunction.

TABLE OF CONTENTS

1

ETHICS.................................................................................................................... 11

2

INTRODUCTION.................................................................................................... 12

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3

STUDY OBJECTIVES........................................................................................... 14

4

INVESTIGATIONAL PLAN................................................................................... 15

4.1 OVERALL STUDY DESIGN AND CHOICE OF CONTROL GROUP........ 15 4.2
METHODOLOGY ........................................................................................... 15 4.3
SELECTION OF STUDY POPULATION ...................................................... 17
4.3.1
INCLUSION CRITERIA.......................................................................... 17
4.3.2
EXCLUSION CRITERIA ........................................................................ 17
4.3.3
WITHDRAWAL CRITERIA................................................................... 18
4.3.4
DROP OUT / LOST TO FOLLOW UP CRITERIA................................ 19
4.4
TREATMENTS ADMINISTERED................................................................. 19
4.4.1 IDENTITY OF INVESTIGATIONAL PRODUCT................................. 19 4.4.2
DOSES AND ADMINISTRATION......................................................... 20 4.4.3
BLINDING AND RANDOMISATION................................................... 20 4.4.4
PRIOR AND CONCOMITANT THERAPY........................................... 20 4.4.5
TREATMENT COMPLIANCE ............................................................... 20
4.5
EFFICACY AND SAFETY VARIABLES...................................................... 21
4.5.1
PRIMARY EFFICACY VARIABLES..................................................... 21
4.5.2
SECONDARY EFFICACY VARIABLES .............................................. 21
4.5.3
APPROPRIATENESS OF MEASUREMENTS...................................... 24
4.5.4
SAFETY AND TOLERABILITY VARIABLES .................................... 24
4.6 DATA QUALITY ASSURANCE.................................................................... 25 4.7
STATISTICAL METHODS............................................................................. 26
4.7.1 SAMPLE SIZE ESTIMATION................................................................ 26 4.7.2
ANALYSIS POPULATIONS .................................................................. 26 4.7.3
HYPOTHESES......................................................................................... 27 4.7.4
METHODS OF ANALYSIS .................................................................... 27
5 STUDY PATIENTS ................................................................................................ 29
5.1 DISPOSITION OF PATIENTS........................................................................ 29 5.2
PROTOCOL DEVIATIONS ............................................................................ 31
6 EFFICACY EVALUATION .................................................................................... 31
6.1 DATA SETS ANALYSED............................................................................... 31 6.2
DEMOGRAPHIC CHARACTERISTICS........................................................ 31
6.3
PRE-EXISTING CONDITION/CONCOMITANT MEDICATIONS USED IN
STUDY......................................................................................................................... 31
6.4
EFFICACY RESULTS..................................................................................... 32
6.4.1
PRIMARY EFFICACY MEASURES...................................................... 32
6.4.2
SECONDARY EFFICACY PARAMETERS .......................................... 34
7 SAFETY EVALUATION......................................................................................... 40

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7.1 EXTENT OF EXPOSURE............................................................................... 40 7.2
ADVERSE EVENTS........................................................................................ 40
7.2.1
SUMMARY OF ADVERSE EVENTS.................................................... 40
7.3
CLINICAL LABORATORY EVALUATION................................................. 42
7.3.1
VITAL PARAMETERS........................................................................... 42
7.3.2
LABORATORY EVALUATION ............................................................ 42
7.3.3
ECG RESULTS ........................................................................................ 44
7.4
TOLERABILITY.............................................................................................. 44
8 DISCUSSION AND CONCLUSION .................................................................... 45
9REFERENCES....................................................................................................... 48

10 APPENDICES......................................................................................................... 50
10.1 STUDY INFORMATION................................................................................ 50
10.1.1
LIST OF CONCOMITANT MEDICATIONS PROHIBITED................ 50
10.1.2DEFINITION OF SERIOUS ADVERSE EVENT................................... 50
10.1.3
IIEF QUESTIONNAIRE.......................................................................... 51
10.2 TABLES REFERRED TO BUT NOT INCLUDED IN THE TEXT............... 53
10.2.1PROTOCOL DEVIATIONS .................................................................... 53
10.2.2LISTING OF PATIENTS RECEIVING INVESTIGATIONALPRODUCT................................................................................................................ 55
10.3 PRE-EXISTING CONDITION/CONCOMITANT MEDICATION USED IN
THE STUDY ................................................................................................................ 56
LIST OF ABBREVIATIONSAEANCOVA

Adverse Event
Analysis of Covariance

CRF

Case Report Form

ECG

Electrocardiogram

ESR

Erythrocyte Sedimentation Rate

ED

Erectile Dysfunction

EDITS
Hb

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Erectile Dysfunction Inventory of Treatment Satisfaction
Haemoglobin

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IEC

Independent Ethics Committee

IIEF

International Index of Erectile Function

ITT

Intent To Treat

ICH

International Conference on Harmonisation

IP

Investigational Product

LOCF

Last Observation Carried Forward

NAION

Non arteritic anterior optic neuropathy

SAE

Serious Adverse Event

SGPT

Serum Glutamic Pyruvic Transaminase

LIST OF TABLES AND GRAPHS
Table No

Title

Page No.

Table 1

Visit specific schedule

16

Table 2Composition of VigRX Plus

19

Table 3Treatment regimen

20

Table 4

Criteria for global assessment by investigator

23

Table 5

Assessment of tolerability

25

Table 6

Reasons for screening failure

29

Table 7

Demographic characteristics

31

Table 8

Responses to IIEF Q3 and Q4

32

Table 9Effect on IIEF scores

33

Table 10

Effect on IIEF domains

35

Table 11

Effect on EDITS (patient version)

36

Table 12

Effect on EDITS (partner version)

37

Table 13

Effect on sperm count and semen volume

38

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Table 14

Effect on sperm motility

38

Table 15

Effect on Serum testosterone

39

Table 16

Global assessment of therapy by investigator

39

Table 17

Incidence of adverse events

41

Table 18

Assessment of vital parameters

42

Table 19

Assessment of laboratory(blood) parameters

43

Table 20

Assessment of tolerability

44

Graph 1

Effect on IIEF A scores

33

Graph 2

Effect on IIEF total scores

34

Graph 3

Percentage improvement in IIEF domains

35

Graph 4

Effect on EDITS scores (patient version)

36

Graph 5

Effect on EDITS scores (partner version)

37

Graph 6

Subjects’ opinion

40

Fig 1

Study design

17

Fig 2

Disposition of subjects

30

1 ETHICSThe study was conducted in accordance with International Conference of Harmonization’s(ICH)-Good Clinical Practices (GCP) and the applicable regulatory requirements of India.
Prior to study initiation, the study protocol and amendments were submitted to an
appropriately constituted Independent/ Institutional Ethics Committee (IEC), in agreementwith local legal prescriptions, for formal approval of the study conduct. The study
commenced only after an affirmative decision of the EC/IRB concerning the conduct of thestudy was made in writing to the investigator and a copy provided to the sponsor. Freely
given informed consent was obtained from study participants and their female partners
prior to their entry into the trial.
Study Site

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Ethics Committee

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Dr. Gaurang Shah
Jivdaya Hospital,
Dharmoday bldg,
Jivdaya lane, L.B.S. Marg,
Ghatkopar(W), Mumbai-86.
Mob: 9821019432.
Dr. Suresh Patankar
Institute of urology,
Survey no. 32/2A, Erandwane,
Behind Mehendale garage,
Gulwani Maharaj road, Pune-4.
Mob : 9881256992
Dr. R. K. Shimpi
Dept. of Urology,
Noble Hospital, 153,Magarpatta
City Road,
Hadapsar, Pune
411 013.
Mob : 9822059799

Version 1.2

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Independent Ethics Committee
4, Sharavati, Worli Sea Face, Worli, Mumbai
400030.
Tel : 91-22-65748188
Fax : 91-22-24966602
Ethical Committee, AMAI Charitable Trust
C/O Institute of Urology
S.No. 32/2A, Erandwane,
Behind Mehendale Garage,
Gulwani Maharaj Street,
Pune 411004.
Ethical Committee,
Noble hospital,
153,Magarpatta City Road, Pune
- 411013.
Tel: (020)66285000 / 66295000
Fax: (020)66285199

2 INTRODUCTION
It has been reported from various studies in the general population and primary care thataround 15-20% of men describe some sort of sexual problem 1. Erectile dysfunction is
one of the most common forms of sexual disorder and according to a survey, theMassachusetts Male Aging Study, 52% of men beyond 40 years of age may have somedegree of erectile failure2.

Current pharmacologic treatment of male sexual dysfunction includes a number ofinterventions; including oral phosphodiesterase type 5 (PDE5) inhibitors andintracorporeal agents with vasodilatory effects 3. PDE5 inhibitors (e.g Sildenafil) for
erectile dysfunction have revolutionised the treatment of male sexual dysfunction andare among the best selling drugs worldwide4. While normal sexual function involves
successful integration of biological, psychological, and interpersonal influences 3,
Sildenafil is known only to facilitate erections and not restore sexual desire (does notwork without sexual stimulation), overcome sexual resistance or treat relational discord 4.

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The use of Sildenafil necessitates caution in cardiac failure and when used within six
months of acute myocardial infarction and stroke. It is inadvisable in patients withunstable angina pectoris. The co-administration of Sildenafil with organic nitrates, forexample, glyceryl trinitrate or isosorbide dinitrate, is unsafe. The relative
contraindications to Sildenafil in cardiovascular disease are uncontrolled hypertension
and impaired cardiac reserve. The most common side effects are headache, flushing(due to vasodilation), and dyspepsia (due to relaxation of the smooth muscle of thegastroesophageal sphincter with reflux 5. Further, several cases of non-arteritic anterior
ischaemic optic neuropathy (NAION) have been reported since 2005 in users of PDE5
inhibitor agents. Following a series of such case reports, WHO and FDA have labeled
the association between use of PDE5 inhibitors and risk of NAION as “possibly” causal 6.
While concerns of safety and limited efficacy still remain as longstanding treatment gaps
in current therapy for male sexual dysfunction, several herbal therapies have provided
suggestive evidence of efficacy in controlled clinical trials. The present study was therefore
undertaken to evaluate the safety and efficacy of an herbal formulation VigRX Plus
containing Korean red ginseng a widely used herbal ingredient and others in subjects withmale sexual dysfunction. The study was based on the initial aphrodisiac activity exhibitedby VigRX Plus in significantly reducing the ejaculation latency and post ejaculatory interval
in male albino rats when compared to vehicle control. Treatment with VigRX Plus had
resulted in a significant increase in ejaculation frequency on day 7 and a non significant
increase on day 14 with marginal increase in testosterone concentration in serum andnumber of spermatogonia cells in seminiferous tubules of testes. (Unpublished report).
A set of preclinical studies 7 (at two different doses and duration) of an earlier marketed
herbal combination VigRX, (devoid of 3 additional ingredients-Tribulus, Damiana, andBioperine that are present in VigRX Plus) in a Sprague-Dawley rat model demonstrated amarked enhancing effect on the sexual activity of rats. In vitro assays determined that
VigRX is able to inhibit the enzyme Rho-kinase. Also, VigRX was shown to be free frompharmaceutical adulterants, including phosphodiesterase type 5 (PDE -5) inhibitors andrelated analogues.

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With the accrued preclinical evidence it was imperative to investigate the role of VigRx
Plus in humans. Hence, in the present study, efficacy and safety of VigRX Plus was
explored in human male subjects with sexual dysfunction.

3 STUDY OBJECTIVES
Primary objectives
To evaluate the efficacy of VigRX Plus capsules as a dietary supplement to improve
erectile function as assessed by Erectile function subscale of IIEF Questionnaire (IIEFA)
from baseline to end of treatment as compared to placebo. Index) questionnaire ascompared to placebo
Secondary objectives• To evaluate the efficacy of VigRX Plus capsules as a dietary supplement for Male
Sexual Health as assessed by IIEF (Total) (International Index of Erectile Function)questionnaire from baseline to end of treatment as compared to placebo• To evaluate the efficacy of VigRX Plus capsules as a dietary supplement for Male
Sexual Health as assessed by IIEF-B questionnaire (sum of all the subscales of IIEF
except erectile function subscale) from baseline to end of treatment as compared toplacebo• To evaluate the impact of VigRX Plus capsules as a dietary supplement for Male
Sexual Health as assessed by EDITS questionnaire (Patient & Partner version) as
compared to placebo• To evaluate the safety of VigRX Plus capsules as a dietary supplement for Male
Sexual Health from baseline to end of treatment as compared to placebo• To assess the effect of VigRX Plus on the sperm count, motility, semen volume frombaseline to end of treatment.
• To assess the effect of VigRX Plus on Serum testosterone from baseline to end oftreatment as compared to placebo.

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4 INVESTIGATIONAL PLAN
4.1

OVERALL STUDY DESIGN AND CHOICE OF CONTROL GROUP

This was a multicentre, triple blind, randomized, parallel group study of VigRX in subjects
with male sexual dysfunction. The control used for this study was placebo.
4.2

METHODOLOGYThis was a twelve week study wherein subjects after a wash out period of 7/15 days,
were randomized to receive either VigRX Plus or placebo capsules (Fig1) After theirentry into the trial, eligible subjects were administered IIEF questionnaires for baseline
assessment of sexual dysfunction. Safety assessment through medical history, vitals
and systemic examination, monitoring of adverse events were performed at baseline andeach follow up visit. Follow up visits were scheduled on Day 28, Day 56, Day 84 ofstudy. At each of these visits, in addition to the IIEF evaluation subjects administered an
EDITS (patient version) questionnaire to assess treatment satisfaction. EDITS (partner
version) data on female partners of trial subjects was acquired on day 28 and day 84.
Efficacy evaluation by semen analysis parameters (semen volume, sperm count, andsemen motility) and serum testosterone was done at screening visit and at end oftreatment.
Laboratory evaluation and ECG were scheduled at start and end of treatment. Global
assessment of therapy by investigator, subjects’ opinion and assessment of tolerability
were performed at treatment end (Day 84).

A detailed schedule of study visits and procedures are displayed in Table 1
Table 1. Visit specific schedule
Param eters

Screening

Baseline(Day -7/-15)(Day 1)

X

Day 28

Day 56

Day 84

-

-

-

-

-

-

X

-

-

X

X

X

X

X

X

X

X

X

X

X

-

-

-

-

Subject Inform ed
Consent
Subject’s Fem ale
Partner Inform ed
Consent
VitalsSystem ic Exam ination

TSH

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S. Prolactin

X

-

-

-

-

S. Testosterone

X

-

-

-

X

CBC & ESR

X

-

-

-

X

ECG

X

-

-

-

X

Serum Creatinine

X

-

-

-

X

Urine Routine

X

-

-

-

X

RBS

X

-

-

-

-

SGPT

X

-

-

-

X

Sem en Analysis

X

-

-

-

X

X

X

X

X

X

-

-

X

X

X

-

-

X

-

X

-

X

X

X

X

-

X

X

X

-

-

X

X

X

X

-

X

X

X

-

-

-

X

IIEF T Questionnaire
EDITS Questionnaire(patient version)
EDITS Questionnaire(partner version)
Subject Diary
Dispensing of Study
Medication
Monitoring ofAdverse / Serious
Adverse Events-

IP com pliance
Global assessment by theinvestigator-

Fig 1 : Study design

Activ eScreening

R

PlaceboDay (-7 / -15)

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Day 1

Day 28

Day 56

Day 84

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SELECTION OF STUDY POPULATION

4.3.1

INCLUSION CRITERIAPatients satisfying all of the following inclusion criteria were to be included in the study
1. Male aged between 25-50 years
2. Subject having a monogamous, heterosexual relationship
3. Male subjects with IIEF-A score 11 to 23 & IIEF-B score 21 to 35 at screening visit &baseline visit
4. Subject provides written informed consent and comes for regular follow up
4.3.2

EXCLUSION CRITERIAPatients meeting any of the following exclusion criteria were to be excluded from thestudy
1. Subjects with major psychiatric disorders
2. Has a history of stroke, myocardial infarction, coronary artery disease, cardiac
failure, angina, life-threatening arrhythmia within the past 6 months.
3. Has a history of diabetes
4. Has a history of spinal cord injury or a radical prostatectomy or radical pelvic surgery.
5. Has anatomical deformity of the penis which has a severe effect on sexualfunctioning
6. Is a k/c/o HIV / AIDS
7. Is know to suffer from sexually transmitted diseases(STDs) at screening visit
8. Chronic Alcoholics showing withdrawal symptoms or subjects having medication(opiates etc) or drug (marijuana, cocaine etc)/ Nicotine/Caffeine dependence
9. Is using medications that are known to cause sexual dysfunction (cimetidine,spironolactone, thiazides, β-adrenergic blockers, anti- depressants etc.)
10. Has a major illness that in the opinion of the investigator would interfere with theconduct of the study.
11. Has participated in a clinical drug study within the last 30 days prior to entering thisstudy. Read more on http://www.vigrxplusdirect.com/

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12. Subject with Liver dysfunction as evidenced by SGPT level of 1.5 X ULN.
13. Subject with Renal dysfunction as evidenced by Serum Creatinine level of 1.5 X
ULN.
14. Has an abnormal thyroid stimulating hormone (TSH) level lower than 30% of LLN or
more than 30% of ULN.
15. Has erectile dysfunction caused by neurological or endocrine factors such as
hyperprolactinemia or low serum testosterone levels (<200 ng/dl).
16. Subjects already taking any medications for the study indication & do not wish to
discontinue the same
17. Subject not ready to sign the consent & unable to comply with the protocol
18. Subjects whose female partners are Pregnant

4.3.3

WITHDRAWAL CRITERIA

Subjects meeting any of the following criteria were to be withdrawn from the study•

Earnest request of the subject assigning a reason for the same.

•

Discretion of the Investigator.

•

Repeated protocol criteria deviations.

•

Serious adverse events where continuation of study possess serious risk to thesubject.

•

Subject has consumed less than 80% of the total dose that needs to be
consumed in the period between follow-ups and in the opinion of the investigatorneeds to be withdrawn from the study•

Subject consumes any other medicines used for the treatment of Sexual
Dysfunction.

•

Subject consumes any medications that are mentioned in the list of prohibited
medications.
4.3.4

DROP OUT / LOST TO FOLLOW UP CRITERIA

Subject was to be considered as a dropout if he does not report for the follow up within –5 or + 5 days of his scheduled visit day but does report to investigator later and in theopinion of the investigator needs to be consider as drop out.
Subject was to be considered as a lost to follow up if he does not report to investigator at
all after a particular follow up visit during therapy period.

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TREATMENTS ADMINISTERED

4.4.1

IDENTITY OF INVESTIGATIONAL PRODUCTEach capsule of VigRX Plus contains the following
Table 2.Composition of VigRX Plus
Ingredients (Latin
Names)Part used

Actual wt / caps(mg)

Panax ginseng (Korean Red Ginseng)
Serenoa repens (Saw Palmetto)

Root
Berry

100.000
100.000

Crataegus rivularis ( Hawthorne)

Berry

100.000

Ginkgo biloba

Leaf

100.000

Turnera diffusa (Damiana)

Leaf

100.000

Tribulus terrestrisVine

075.000

Erythroxylum catuaba

Bark

050.000

Ptychopetalum olacoides (Muira Puama)Bark

050.000

Cuscuta chinensis
Epimedium sagittatum

Seed
Leaf

025.000
015.000-

005.000

Bioperine (extract from Piper nigrum fruit )Total amount

720.000

Additional ingredients: dicalcium phosphate, cellulose, croscarmellose sodium, stearicacid, silicon dioxide, magnesium stearate, FD&C Red #40
Presentation: White plastic bottles each containing 128 capsules
Placebo capsules were similar to IP in appearance and were made up of CMC(Carboxymethyl cellulose)
4.4.2

DOSES AND ADMINISTRA TION

VigRX Plus Pills and placebo were to be taken orally with meals at a dose of 2 capsules
twice daily for 12 weeks. Each capsule contained 360 mg of the active composition
mentioned above. The IP and placebo were administered to subjects in the following
regimen.
Table 3. Treatment regimen
Group

Morning

Night

Route of
Administration

Treatment
Duration

VigRX
Plus

2Capsules* of
VigRX Plus

2 Capsules* of
VigRX Plus

ORAL

12 weeks(from day 1

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2 Capsules of
2 Capsules of(Capsules to be
Placebo
Placebotaken with meals)*Each capsule contained 360 mg of the active composition of VigRx Plus
Placebo

4.4.3

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today 84)BLINDING AND RANDOMISATION

A total of 72 subjects were expected to be recruited from the investigator’s clinical practices
or referring physicians. Each subject satisfying the inclusion/exclusion criteria was to be
recruited in the study and be assigned to one of the treatment groups according to arandomization schedule. A research coordinator, who was not directly involved in trialrelated activities, performed the randomization and blinding to avoid bias.
4.4.4

PRIOR AND CONCOMITANT THERAPY

During the course of the study, the subjects were prohibited from consuming any othermedication used in the treatment of Male Sexual Dysfunction. A list of medications
prohibited in the study is provided in Appendix 10.1.1. No other herbal medication otherthan that dispensed during the study was allowed. Subjects who were required to takemedicines for any other complaints were to do so only in consultation with the Investigator.
Use of any concomitant medication was to be recorded in the case report form (CRF).
Subjects were not advised any specific lifestyle & dietary changes upon enrolment in the
study & throughout the duration of the study.
4.4.5

TREATMENT COMPLIANCE

In order to ensure treatment compliance, adequate instructions were to be given to
subjects regarding trial procedures during the informed consent process. Subjects were
provided with a memory card for follow up visits and test requisition forms for laboratory
investigations. At each visit, a record of dispensed and returned medication was to be
maintained to determine subject’s compliance to treatment.

4.5

EFFICACY AND SAFETY VARIABLES

4.5.1 PRIMARY EFFICACY VARIABLES
4.5.1.1

INTERNATIONAL INDEX OF ERECTILE FUNCTION -ERECTILE FUNCTION
DOMAIN (IIEF-A)

It is an internationally accepted instrument described by Rosen et al 8 for measuring
erectile dysfunction and monitoring response to treatment.
Read more on http://www.vigrxplusdirect.com/

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The erectile function domain (items1-6 of the index) designated as IIEF A in this study
was used to measure erectile dysfunction. It provided information on the subject’s ability
to achieve and maintain an erection. The erectile function domain consists of six
questions concerning erection frequency (question [Q]1), erection firmness (Q2),frequency of partner penetration (Q3), frequency of maintaining erection after
penetration (Q4), ability to maintain erection to completion of intercourse (Q5), andconfidence in achieving and maintaining erection (Q6), all during the previous 4 weeks.
The primary efficacy variable consisted of the change in mean erectile function domainscore (IIEF A) from baseline to end point.

4.5.2 SECONDARY EFFICACY VARIABLES
4.5.2.1

INTERNATIONAL INDEX OF ERECTILE FUNCTION- TOTAL (IIEF-TOTAL)The IIEF addresses the relevant domains of male sexual function (erectile function,orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), is
psychometrically sound, and has been linguistically validated in 10 languages. This
questionnaire is readily self-administered in research or clinical settings. The IIEF
demonstrates the sensitivity and specificity for detecting treatment-related changes inpatients with erectile dysfunction8.

Each item on the IIEF questionnaire is scored on 5 point Likert scale. Scores for eachdomain are variable and total score range is 5 to 75. Maximum possible score for erectile
function is 30. The complete IIEF questionnaire is provided as Appendix 10.1.3
4.5.2.2

INTERNATIONAL INDEX OF ERECTILE DYSFUNCTION (OTHER THAN THE
ERECTILE FUNCTION DOMAIN)-(IIEF B)

The section of the international index other than the erectile function domain, designatedas IIEF B in this study, was used to measure other aspects of sexual dysfunction
besides erectile dysfunction. It gives information on, orgasmic function, sexual desire,intercourse satisfaction and overall sexual satisfaction in a subject.

4.5.2.3 ERECTILE DYSFUNCTION INVENTORY OF TREATMENT SATISFACTION (EDITSPatient and Partner version)

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Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) was developed by
Althof, Corty et al 9 to examine the degree of satisfaction with different treatment
modalities for ED. Separate questionnaires are available for both the subject and thesubject’s partner. With the partner version EDITS allows partner satisfaction an
important determinant—especially for sexual dysfunction but seldom evaluated to bemeasured and investigated.

4.5.2.4

SEMEN ANALYSIS

Semen analysis is a measure to determine the semen quality in terms of the ability ofsperm to accomplish fertilization. A semen analysis does not diagnose fertility or
infertility but provides a relative measure of semen quality compared to the general
population of men. Since it is the sperm that is of importance to male fertility, semenquality involves both sperm quantity and quality.
Most available studies on oral phosphodiesterase inhibitors demonstrate a significant
increase in sperm motility and viability both in vivo and in vitro, which seems to beenhanced at low doses and reduced at high concentrations 10. In the current study
semen analysis of subjects was conducted at screening and end of treatment toinvestigate whether administration of the VigRX Plus has any modifying effect on
seminal parameters .
The following parameters were measured in semen analysis: oconsistency of semen oVolume andSperm count: Sperm count measures theconcentration of sperm in a man's ejaculate. Anything over 20 million sperm
per milliliter is considered normal.
oSperm motility describes the ability of sperm to move properly towards an ovum.
A more specified measure is motility grade, where the motility of sperm are
divided into four different grades:

Grade IV: Sperm with progressive motility. These are the strongest and swim fast in astraight line.
Grade III: (non-linear motility): These also move forward but tend to travel in a curved or
crooked motion.

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Grade II: These have non-progressive motility because they do not move forward
despite the fact that they move their tails
Grade I: These are immotile and fail to move at all
The percentage of each motility grade was recorded after 1h, 2h, 3h and 6h of collection.
4.5.2.5

SERUM TESTOSTERONE

While the role of testosterone in mediating penile erection may be largely unknown,routine testing of serum testosterone has been recommended for initial evaluation of ED.
In this study serum testosterone levels were evaluated for changes from baseline to
endpoint (Day 84) across the two study groups.
4.5.2.6

GLOBAL ASSESSMENT OF THERAPY BY INVESTIGATOR

Global assessment of therapy was made by the investigator, based on the criteria
described below:
Table 4. Criteria for global assessment by investigator
Excellent
Very Good

Improvement in all the IIEF-A, IIEF-B, EDITS (patient & partner versions)
Questionnaires , Semen Analysis & Serum testosterone
Improvement in IIEF-A, IIEF-B, EDITS (patient version) Questionnaires& Semen Analysis

Good

Improvement in IIEF-A, IIEF-B, EDITS (patient version) Questionnaires

Fair

Improvement in IIEF-A & IIEF-B Questionnaires

Poor

No Improvement

4.5.2.7

SUBJECT’S OPINION

At the end of the study period, subjects were asked if they preferred to continue using of
the study product in future, for their sexual dysfunction

4.5.3 APPROPRIATENESS OF MEASUREMENTS
The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional
self-report instrument for the evaluation of male sexual function. It is has been
recommended as a primary endpoint for clinical trials of erectile dysfunction (ED) and for
diagnostic evaluation of ED severity. The IIEF was developed in conjunction with the

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clinical trial program for Sildenafil, and has since been adopted as the 'gold standard'measure for efficacy assessment in clinical trials of ED and its use in classifying ED
severity and prevalence. The IIEF meets psychometric criteria for test reliability andvalidity, has a high degree of sensitivity and specificity, and correlates well with othermeasures of treatment outcome. It has demonstrated consistent and robust treatment
responsiveness in studies in USA, Europe and Asia, as well as in a wide range of
etiological subgroups 11.

Limitations11- The IIEF focuses only on current sexual functioning and provides
superficial assessment of domains of sexual functioning other than erection. It does notprovide any specific information about the partner relationship or sexual functioning of
the partner. It could be argued that these are important areas for assessment in clinicalpractice. It was thus important to include EDITS questionnaire to assess treatment
satisfaction of the partner.

4.5.4 SAFETY AND TOLERABILITY VARIABLES
Safety was assessed primarily through incidence of adverse events (AE), clinical andlaboratory evaluation of the subject.
4.5.4.1

ADVERSE EVENTSAn adverse event is defined as any untoward medical occurrence in a subject who has
been administered an investigational product and does not necessarily have a causal
relationship. An adverse event can therefore be any unfavourable and unintended sign(including an abnormal laboratory finding), symptom or disease temporarily associatedwith the use of the IP whether or not related to the IP.
Adverse events were further classified into serious and non-serious. Definition of serious
adverse events (SAE) is described in Appendix 10.1.2 of this report. All adverse events
whether serious or non serious, whether observed or reported by the patient were to beevaluated by the investigator and recorded in the AE section of the subject’s case reportform. Adverse event reporting required the severity of the event, treatment administered,any change in study drug, investigator attribution to study drug and outcome status to be
documented in the CRF.

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CLINICAL AND LABORATORY EVALUATION

Physical examinations and monitoring of vital signs (systolic and diastolic bloodpressure, respiration rate and pulse rate) were to be conducted at screening, baseline
and at each follow up visit. Laboratory evaluations consisting of haematological, clinicalchemistry and urinalysis parameters were required at the screening visit and at the endof treatment phase on Day 84. In addition, a 12-lead Electrocardiogram (ECG) was to be
performed at these visits. Any clinically significant abnormality in any of the above
mentioned safety parameters was to be recorded as an adverse event in the respective
pages of the CRF.
4.5.4.3

TOLERABILITY

In addition to the above mentioned safety parameters, subjects were asked to rate thetolerability of the IP based on the following criteria at the end of the treatment: Table 5.
Assessment of tolerability
Good

No side effects

Fair

Mild to moderate side effects

Poor

Severe side effects requiring withdrawal of subject

4.6

DATA QUALITY ASSURANCE

Before study initiation, it was ensured that the protocol -stipulated study procedures were
well-understood by the investigator and his study staff .The study was monitored
regularly for compliance to ICH-GCP, protocol and regulatory requirements. At eachmonitoring visit, CRF entries were verified by comparing them with the source
documents before retrieving the case report forms. The monitor was to ensure that theinvestigator maintained accurate, timely, and complete records.

4.7

STATISTICAL METHODS

4.7.1 SAMPLE SIZE ESTIMATION
For this exploratory pilot study, it was estimated that a sample size of 60 subjects would
be sufficient to detect a difference in IIEF scores between VigRX Plus and placebo groupat a significance level of 5%.

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4.7.2 ANALYSIS POPULATIONS
Two types of populations were identified for analysis
Intention –To -Treat Population (ITT) population were subjects who were recruited into thestudy and who received at least one dose (or any portion of a dose) of study m edication.
Analysis of safety variables were done for the ITT population.
Per-Protocol (PP) population consisted of completed subjects i.e. all subjects whocompleted the study according to the following definition:
Definition for a completed case: Subject was considered a completed case if he fulfilled
at least 84 days of treatment. (w.r.t. IIEF & EDITS patient version) Note:•

For this study even those subjects whose female partners did not participate,were considered as completed subjects & their data were to be analyzed.

•

EDITS partner version assessment was to be done for only those female
partners who gave informed consent and for whom data was available.

Drop out, withdrawal and protocol deviation cases were to be reported and described.
Missing, unused and spurious data were to be identified and appropriately taken care ofduring the final analysis. Missing data was to be inserted using the last observation carriedforward (LOCF) method.
4.7.3 HYPOTHESESThe null hypothesis (H0) was that no difference exists in both primary and secondary end
points between both the groups and the alternative hypothesis (HA) was that there exists
a difference between the groups

Primary hypothesis:
1. The score of IIEF-A will increase from baseline to Day 84.
2. This increase will be more in the active group as compared to placebo group.

Secondary hypotheses:
The secondary hypotheses to be investigated were•

Levels of secondary response variables improve from Day 1 up to day 84 (to betested per variable).

•

The safety variables (CBC, ESR, Liver Profile, Renal Profile, & ECG) may notchange from screening to day 84

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4.7.4 METHODS OF ANALYSIS•The final analysis was performed at the end of the study (Day 84) after database
lock.

•

Basic statistic evaluations include mean, standard deviation, median, min-max,
etc…

•

All efficacy and safety variables were exploratively analyzed and descriptively
evaluated. Thereby the structure equality of the 2 arms was especially verified.
Thus, initially univariate and co-variate analysis of all the variables (qualitative,
quantitative and ordinal) was carried out to determine the basic features of datalike range, central tendency, spread etc. Then all the variables were comparedacross the groups to see the broad differences between them.

•

Descriptive statistics (mean, standard deviation and N for continuous and countvariables; median, range and N for discrete variables) of the primary response
variable (IIEF - A) and each of the secondary response variables was done using
all data available.

•

The primary endpoint the Erectile Function subscale of International Index of
Erectile Function Questionnaire (IIEF-A) was compared between the treatment
and placebo groups at baseline & end of treatment. Secondary Efficacy variables(IIEF-total, IIEF-B, EDITS Patient & Partner version, Semen Analysis, S.
Testosterone) were also compared between the treatment and placebo groups atbaseline & end of treatment. These were the quantitative variables and weremainly assessed by quantitative statistics. Adequate statistical tests such as the ttest (paired for before and after data, unpaired if between the two groups),
chisquare test, U-test, ANOVA, ANCOVA etc, were applied. Friedman/ Wilcoxon(for before and after data) Mann-Whitney (between the two groups)
nonparametric test were used to confirm these results.

•

Nominal variables in the study such as global assessment of therapy wereassessed by the chi-square test.

•

All statistical tests were performed at 5% significance level (p < 0.05).

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For demographic and other remaining variables (vital parameters, clinicalexamination, and lab tests which include Complete Blood Count (CBC), ESR,
SGPT, Creatinine and Routine Urine) are concerned, initially univariate analysis
was carried out. They were then compared across the groups by adequate
statistical tests such as the t test, chi-square test, U-test, etc.

•

Adverse/Serious Adverse Events were analysed using appropriate statistical test.

•

The following statistical softwares were used: - SPSS 15, PEPI, EPI INFO 2000
and MS Excel XP.

Interim Analysis and Data Monitoring
No interim analysis was planned for the trial.

5 STUDY PATIENTS
5.1

DISPOSITION OF PATIENTSOut of 108 patients screened, 78 were recruited into the study. Failure to meet the
stipulated IIEF scores and laboratory abnormalities were the major reasons for screening
failures (Table 6). The eligible subjects were randomized to receive either VigRX Plus orplacebo. While one subject from the placebo group (VL/DM/63) was withdrawn due tohis unwillingness to continue participation in the study after Day 56, twoothers(VL/DM/37and VL/DM/20 were lost to follow up after Day 28 and Day 56.
Fig 2.displays the disposition of subjects in the study.
Table 6. Reasons for screening failure
Site ID
IIEF
Laboratory abnormalities

Other

VL/DM/01

4

3

0

VL/DM/02

0

6

2

VL/DM/03

1

0

1

VL/DM/04

0

2

1

VL/DM/05

3

3

2

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Fig 2. Disposition of patients
5.2

PROTOCOL DEVIATIONSThere were no major protocol violations which led to withdrawal of subjects from thestudy. A majority of the protocol deviations were related to due to delay in scheduledlaboratory test or tests not conducted due to various reasons. Appendix 10.2.1
summarizes the protocol deviations at each study site.

6 EFFICACY EVALUATION
6.1

DATA SETS ANALYSED

Analysis of safety (vital parameters) was done on an ITT population consisting of data on
78 subjects in whom at least one post baseline measurement was available. Analysis of

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laboratory parameters however was done only on subjects in whom complete data wasavailable for screening and end of treatment visit.
Efficacy evaluation was performed on a per-protocol data set of completed cases, inwhich data on all the protocol stipulated visits was available for IIEF and EDITS
questionnaires. Analysis of all other efficacy parameters were done for subjects in whomcomplete data is available for the respective parameter

6.2

DEMOGRAPHIC CHARACTERISTICS

The two study groups appeared to be well balanced in terms of mean age of theirsubjects. (Table 7)
Table 7. Demographic characteristics
Demographic characteristics
Age (yrs.)

VigRx Plus
(N=39)

Placebo (N=39)

35.23 ± 13.24

34.33 ± 11.78

Values are expressed as mean ± 2SD

6.3 PRE-EXISTING CONDITION/CONCOMITANT MEDICATIONS USED IN
STUDY

A list of concomitant medications used in the study is provided in Appendix 10.3. Allconcomitant medications used were indicated for pre-existing conditions of the subjects
or for treatment of adverse events.

6.4

EFFICACY RESULTS

6.4.1
6.4.1.1

PRIMARY EFFICACY MEASURES

IIEF A

Treatment with VigRX Plus showed a statistically significant (p=<0.0001) increase of IIEF
A erectile function scores from baseline to endpoint at Day 84 as compared to placebo.
In subjects receiving VigRXPlus the ability to penetrate the partner (Q3 of IIEF) andmaintain erection after penetration (Q4 of IIEF) saw a greater improvement than in thosereceiving placebo (Table 8).
Table 8. Responses to IIEF question 3 and 4

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Baseline

Day 8408/05/2010

Improvement

Ability to penetrate the partner (Q3 of IIEF)
VigRX Plus
(N=39)

2.69 ± 1.12

4.12 ± 1.6

58.97 %

2.64 ± 1.08

2.63 ± 1.38

4.86 %

Placebo(N=36)

Ability to maintain erection after penetration(Q4 of IIEF)
VigRX Plus
(N=39)

2.56 ± 1.1

4.02 ±1.6262.82 %

2.44 ± 1.1

2.66 ± 1.34

10.18 %

Placebo(N=36)

IIEF scores are expressed as Mean ±2SD

Table 9. Effect on IIEF scores
Baseline

Day 28

Day 56

Day 84IIEF A
VigRX Plus
(N=39)
Placebo(N= 36)16.08 ± 5.82

20.03 ± 6

22.46 ± 7.14

25.08 ± 9.12

15.86 ± 6.48

16.33 ± 6.98

16.39 ± 7.42

16.47 ± 8.5

IIEF TOTAL
VigRX Plus
(N=39)
Placebo (N= 36)

42.56 ± 10.18

52.15 ± 10.96

58.05 ± 14.54

63.13 ± 20.12

42.47 ± 10.20

43.86 ± 10.66

43.69 ± 6.95

43.86 ± 16.9

IIEF B
VigRX Plus
(N=39)
Placebo (N= 36)

26.49 ± 5.92

32.13 ± 6.34

35.59 ± 8.46

38.05 ± 11.38

26.61 ± 5.82

27.53 ± 6.36

27.31 ± 8.58

27.39 ± 9.84

IIEF scores are expressed as mean ± 2SD

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Effect on IIEF A scores

30

*

25

20
15
10
5
0
VigRx Plus (N=39)
Baseline

Day 28

Placebo (N= 36)
Day 56

Day 84Graph 1.Effect on IIEF A scores.*p=<0.0001 indicates significantly different from baseline, ascompared to placebo by ANCOVA

6.4.2
6.4.2.1

SECONDARY EFFICACY PARAMETERSIIEF TOTAL SCORE

Effect of VigRX Plus in increasing total IIEF scores from baseline to end of treatment (atDay 84) was statistically significant over that of placebo. (Graph 2.)

Effect on IIEF-Total
70

*

60
50
40

30
20
10
0
VigRx Plus(N=39)
Baseline

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Graph 2.Effect on IIEF Total scores. *p<0.001indicates significantly different from baseline ascompared to placebo, by ANCOVA.

6.4.2.2

IIEF BOn Day 84, subjects of the VigRX Plus group saw a statistically significant increase(p=<0.0001) of IIEF B scores from baseline as compared to placebo. Improvement in
IIEF B scores is described in Table 9.
Orgasmic function
Subjects on VigRX Plus saw a greater improvement of orgasmic function than in thoseon placebo as assessed by the increase in question 10 and 11 of the international index.
Sexual desire
Enhancement of sexual desire was greater in subjects of the VigRX Plus group ascompared to those of the placebo group. Overall satisfaction
Scores of overall satisfaction were higher in the VigRX Plus than in the placebo group.

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Table 10. Effect on IIEF domains
IIEF
DOMAINS

Erectile
functionIntercourse
satisfaction
Orgasmic
function
Sexual desire
Overallsatisfaction

VigRX Plus (N=39)

Placebo (N=36)

Baseline(Mean±2SD)

Day 84(Mean±2SD)

ImprovementBaseline(Mean±2SD)

Day 84(Mean±2SD)

Improvement

Q1-6

16.08 ± 5.82

25.08 ± 9.12

60.35%

15.86 ± 6.48

16.47 ± 8.5

2.07 %

Q7
Q8

1.92±1.06
2.69±0.56

3.17±1.37
4.20±0.871.43%

1.94±2.42
2.61±1.08

2.38±1.29
2.66±1.34

14.03%

Q9
Q 10
Q 11
Q12
Q13

2.66±0.52
4.58±0.49
3.25±0.63
3.17±0.55
3.17±0.55

4.20±0.80
4.84±0.36
4.38±0.93
4.51±0.68
4.53±0.68

2.58±1.1
4.44±1.2
3.33±1.58
3.25±1.26
3.22 ±1.26

2.66±1.34
4.58±1.20
3.19±2.28
3.22±1.52
3.19±1.48

2.94±0.82
2.66±1.34

2.91±1.1
2.55±2.04Q14
2.82±0.50
4.10±0.91Q152.64±0.70
4.07±0.87
IIEF scores are expressed as Mean±2 SD

22.49%
47%
61%-0.46%
2.08%-3.7%

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80
70
60

50
40

VigRx Plus

30

Placebo

20
10
0
-10

Erectile
functionIntercourse
satisfaction

Orgasmic
function

SexualdesireOverallsatisfaction

Graph 3. Percentage improvement in IIEF domains

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EDITS

Patient version
In subjects receiving VigRX Plus, EDITS scores on Day 28, 56 and 84 were statisticallysignificantly higher(p<0.0001) than that in those receiving placebo.
The results of EDITS (patient and partner version) are summarized in Table 11 and 12.
Table 11. Effect on EDITS (patient version)
Day 28VigRX Plus (N=39)
65.44 ± 36.28

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Placebo(N= 36)40.17 ± 32

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36.61 ± 39.6

36.78 ± 45.06

EDITS(patient version) scores are expressed as Mean ±2SD

Effect on EDITS scores (patient version)
90

80
70

60

*

*

*

50

40
30

20
10
0
VigRx Plus (N=39)
Day 28

Placebo (N= 36)

Day 56

Day 84Graph 4.Effect on EDITS (patient version) scores. *p<0.001indicates significantly higher thanplacebo, by independent sample t test

Partner version
Female partners of subjects receiving VigRX Plus reported statistically significantly
higher (p<0.0001) scores than those of subjects receiving placebo.

Table 12. Effect on EDITS (partner version)
Day 28VigRX Plus (N=12)69.58 ± 34.24
Placebo(N= 10)25.50 ± 20.24

Day 8482.75 ± 19.6
18.50 ± 18.88

EDITS(partner version)scores are expressed as Mean±2SD

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Effect on EDITS scores (partner version)
90

*

80

*

70
60

50
40

30
20

10
0

VigRx Plus (N=12)
Day 28

Placebo (N= 10)
Day 84Graph 5.Effect on EDITS scores (partner version). *p<0.001indicates significantly higher thanplacebo, by independent sample t test

6.4.2.4

SEMEN ANALYSIS

Sperm count
The mean sperm count in the VigRX Plus group decreased from 49.45 million/ml
at baseline to 47.15 million/ml on day 84 (Table 13). The change however was notstatistically significant as compared to placebo.
Semen volume
The semen volume in both study groups increased from baseline to day 84. The
increase in the VigRX Plus group was not statistically significant as compared toplacebo.
Sperm motility
There was no statistically significant difference between the VigRX Plus and placebogroups with respect to changes in the sperm motility when compared from baseline toend of treatment. (Table 14)

Table 13.Effect on sperm count and semen volume
Sperm count (million per ml)

Semen volume (ml)Baseline

Day 84Baseline

Day 8449.45 ± 55.7

47.15 ± 50.62

1.75 ± 1.26

2.11 ± 1.06

VigRX Plus
(N=22)

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Placebo58.29 ± 60.04(N=18)

63.97 ± 41.66

1.97 ± 1.4

2.22 ± 1.76

Values for sperm count are expressed as Mean±2SD

Table 14. Effect on sperm motility

Sperm
Visit

VigRX Plus

Placebo

Grade of Sperm motility

Grade of sperm motility

Motility
(%)

IV

III

After 1 hr

45±50.68

25±30.54

After 2 hr

42±84.46

After 3 hrI

IV

11±9.2418±40.1051±34124±29.14 11±9.44

17±23.24

28±31.911±11.52

19±42.98

47±28.728±31.22 13±13.22

17±22.02

38±23.1425±35.4416±15.4

21±44.52

44±23.34 29±29.94 17±14.26

19±21.06

After 6 hr

33±19.38

21±26.76

19±21.36

25±47.1

37±24.70 24±25.76 23±20.88

21±21.98

After 1 hr

48±17.39

24±26.54

15±9.98

13±13.32

51±45.22 27±25.02 17±18.94

15±21.74

After 2 hr

43±17.98

28±25.4

16±12.66

16±17.34

43±51.1

27±26.32 19±20.76

21±21.68

After 3 hr

36±30.88

31±29.1

19±7.26

16±14.1638±51.64 30±31.62 20±18.26

23±24.30

After 6 hr

29±15.5230±35.78

20±17.54

20±18.733±48.86 29±42.0

24.62

6.4.2.5

II

III

II

20±19.08

I

SERUM TESTOSTERONEThe serum testosterone levels in subjects receiving VigRX Plus were not statisticallysignificant with respect to change from screening to end of treatment as compared toplacebo. (Table 15)
Table 15. Effect on Serum testosterone
Serum testosterone (ng/dL)

Serum testosterone (ng/dL)

Screening

Day 84544.46 ± 415.28

527.66 ± 310.94

518.1 ± 395.02

471.75 ± 320.76

VigRX Plus
(N=37)
Placebo(N=25)

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S. Testosterone values are expressed as Mean ± 2SD

6.4.2.6

GLOBAL ASSESSMENT OF THERAPY BY INVESTIGATOR

Global assessment of therapy by investigator on Day 84 saw a statistically significant
superiority (p<0.0001) of VigRX Plus over placebo when analysed by Chi-square test.
Table 16. Global assessment of therapy by Investigator
Global assessment of therapy
VigRX Plus Placebo
Excellent

8 (20.15%)--

Very Good

18 (46.15%

--

Good

11(28.21%)2(5.56%)

Fair

----

8(22.22%)Poor

2(5.13%)26(72.22%)

SUBJECT’S OPINION

6.4.2.7

At the end of treatment (Day 84), the proportion of subjects in the VigRX Plus group who
wished to continue receiving the trial medication, was statistically significantly higher
than those in the placebo group.

Subjects' opinion
40
35
30
25
20
15
10
5
0

*

*
VigRx Plus

Placebo
Yes

No

Graph 6.Subjects opinion. *p<0.0001indicates significantly different as compared to placebo, by
Chi-square test

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7 SAFETY EVALUATION
7.1 EXTENT OF EXPOSURE
96.15% of the study population had a maximum exposure to VigRX Plus at a dose of 2
capsules per day for 84 days. The least exposure to VigRX Plus was for 28 days andoccurred in only one subject.
7.2 ADVERSE EVENTS
7.2.1

SUMMARY OF ADVERSE EVENTSOut of a total of 23 adverse events occurring in the study, 11 were reported from the
VigRX Plus group and 12 from placebo group. The most common (7/23) adverse event
was fever of mild severity, with the incidence of the event being similar in both study
groups. A listing of adverse events by treatment group is displayed in Table 17. One
serious adverse event occurred during the entire course of the study. Subject DM05
receiving VigRX Plus suffered from infection due to malarial parasite (Plasmodium
Vivax). The event was severe in intensity and led to hospitalization of the subject. Initiallyreported at the Day 84 visit, the event resolved after a period of eight days on 16.08 09.
The investigator withdrew the subject from the study, but did not consider the event as
related to the study medication.
Table17. Incidence of adverse eventsGroup
Subject
Description of AE

Severity

Onset

ID

Relation to
IP

VigRX Plus
1

DM02

Pruritus

Mild

Day 28Probable2

DM04

Acidity

Mild

Day 28Probable3

DM05

Malaria

SevereDay 84

Not related

4

DM08

Chest Pain

Mild

Day 28Probable

5

DM11

Fever

Mild

Day 28

Not related

6

DM11

Fever

Mild

Day 84

Not related

7

DM19

Fever

Mild

Day 28

Not related

8

DM19

BodyacheMild

Day 28

Not related

9

DM62

Sticky discharge from urine

Mild

Day 84

Possible

10

DM82

Sticky discharge from urine

Moderate

Day 84

Possible

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DM85

Fever

Mild

Day 1

Not related

12

DM01

Cough and cold

Mild

Day 84

Not related

13

DM03

Fever

Mild

Day 28

Not related

14

DM06

Oedema of both lower
extremities

Mild

Day 28Probable

15

DM09

Cough

Mild

Day 28

Not related

16

DM09

Fever

Mild

Day 28

Not related

17

DM09

Fever

Mild

Day 56

Not related

18

DM09

Cough

Mild

Day 56

Not related

19

DM10

Acidity

Mild

Day 84

Not related

20

DM10

Cough

Mild

Day 84

Not related

21

DM17

AcidityModerate

Day 84

Probable22

DM17

Cold and coughMild

Day 84

Not related

23

DM17

Oedema of fingers

Mild

Day 84

Not related

Placebo

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7.3 CLINICAL LABORATORY EVALUATION
7.3.1

VITAL PARAMETERS

Table 18 displays the values for vital parameters assessed at baseline and end oftreatment. In both study groups, there was a statistically significant increase of pulse rate
as compared to baseline. The increases however were not clinically significant. No othersignificant changes of vital parameters were observed in any of the study groups.
Table 18. Assessment of vital parameters
Pulse
rate Respiration rate
(per min)(per min)Baseline
VigRx
Plus(N= 39)74.82 ±
12.8

Placebo75.72(N=39)

10.46

Day84
78.54*
12.04

Baseline± 17.97 ±2.54± 78.05* ±9.92

18.41 ±
4.1

Day84

Systolic
blood
pressure(mm Hg)Baseline

Day84

Diastolic bloodpressure(mmHg)
Baseline

18.21 ± 120.56
1.96
17.46

± 120.77 ±
13.64

78.62
10.42

18.62 ± 122.21
3.3
13.98

±

79.95 ±
9.82

121.44 ±
12.98

±

Day84
79.69 ± 9.64

80.05 ± 9.2

Values of vital parameters are expressed as Mean ± 2SD. * p< 0.05 is significant as compared to baseline bypaired - t test.

7.3.2 LABORATORY EVALUATION
7.3.2.1

HAEMATOLOGICAL PARAMETERS

Changes in the values of haematological parameters are displayed in Table 19.
No significant changes were observed in any of the laboratory safety variables insubjects receiving VigRx Plus. In those receiving placebo, a statistically significant
change occurred in the Day 84 values of a few laboratory parameters when compared tobaseline. Mean eosinophils count increased whereas total RBC count, haemoglobin (Hb),and ESR decreased significantly (p<0.05) in the placebo group. These changes however
were not of clinical importance. Read More on http://www.vigrxplusdirect.com/

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Table 19. Assessment of laboratory (blood) parameters
Hemoglobin (g/dl)
Baseline
Day 84
VigRX
Plus(N=36)
Placebo(N=25)

Total RBC (mill/mul)
Baseline
Day 84

Total WBC (thou/mul)
Baseline
Day 8414.92±2.52

14.94±2.32

5.10±0.86

5.07±0.76

7.50±3.77.14±3.66

15.31±1.82

14.94±1.88*

5.09±0.92

4.86±1.12*7.33±3.5

7.11±3.06

Neutrophils
Baseline

Day 84

Monocytes
Baseline

Day 84

Eosinophils
Baseline
Day 84

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VigRX
Plus
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Placebo(N=25)

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60.33±20.1

58.36±16.94

5.72±4.1

6.11±4.68

4.53±10.24

4.11±6.94

59.52±22.72

57.96±21.7

4.84±3.44

5.08±3.92

3.56±5.8

5.72±10.28

Basophils(%)
Baseline
VigRX
Plus(N=36)
Placebo(N=25)

Version 1.2

Day 84Lymphocytes(%)
Baseline
Day 84

ESR
Baseline

Day 840.36±0.98

0.42±1.1

29±17.56

31±14.2

3.92±6.28

3.22±6.12

0.32±0.96

0.20±0.41

30.32±16.46

31.04±14.92

3.32±2.92

2.80±5.8*

Serum creatinine(mg/dl)

Platelet countBaseline

Day 84Baseline

Day 84Baseline

Day 840.89±0.26

0.90±0.38

255.64±140.76

274.06±121.0
624.72±22.24

26.42±26.72

0.90±0.3

0.97±0.4

243.43±113.12

250.13±90.06

26.16±20.66

26.40±22.48

VigRX
Plus
(N=36)
Placebo(N=25)

SGPT

Values of laboratory parameters are expressed as Mean ± 2SD. * p< 0.05 is significant as compared to baseline by
Wilcoxon signed rank test.

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URIINE ANALYSIS

There was no incidence of any clinically significant findings in the urine routine tests ofboth study groups.

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7.3.3 ECG RESULTS
No clinically significant abnormalities of ECG were reported in any of the study groups.
7.4 TOLERABILITY
There was no statistically significant difference found between the tolerability oftreatment in the two study groups.
Table 20. Assessment of tolerability
Overall assessment of tolerability

VigRX Plus

PlaceboVery good31(79.49%)

28(77.78%)

Good

8(20.51%)5(13.89%)

Fair

---

3(8.33%)

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8 DISCUSSION AND CONCLUSION
The present study was designed to evaluate the efficacy and safety of VigRX plus
capsules in erectile dysfunction and male sexual health. Erectile dysfunction is known toaffect over half of all men between 50 and 70 years of age, and by the age of 40, about
40% of men may suffer from some form of erectile dysfunction12. Although the advent of
PDE5 inhibitors has revolutionized the medical management of sexual dysfunction, amajor limitation to this therapy, along with safety concerns, is the inability to improvesexual desire in men. In this study an attempt was made to address this treatment gap
by evaluating the effect of VigRX Plus in male subjects with sexual dysfunction.
Assessment of efficacy was based on patient reported measures; clinician reported
measures and laboratory evidence. In combination, these outcome measures aimed atevaluating the various aspects that determine the quality of sexual function in men.
The erectile function domain of international index of erectile function (IIEF) was theprimary efficacy parameter of this study. The instrument is widely accepted by regulatory
agencies and scientific journals as a valid and reliable measure of sexual functioning inmen. Treatment with VigRX Plus for 12 weeks led to enhanced quality of erectile
function as evidenced by a statistically significant increase(p=<0.0001) of the IIEF A
scores as compared to placebo. The ability to penetrate and maintain erections
improved by 58% and 62.82% in the VigRX Plus group and 4.86% and 10.18% in theplacebo group.
Improvement in other domains of the international index as assessed by the increase in
IIEF B scores, was also statistically significantly higher (p=<0.0001) with VigRX Plusthan with placebo. Increases in IIEF scores for sexual desire and intercourse satisfaction
were greater in subjects receiving VigRX Plus than in those receiving placebo. Whileorgasmic function and overall satisfaction enhanced by 22.49% and 61% respectively in
VigRX Plus group, the parameters failed to find any improvement in the placebo group.

Overall, the differences in outcomes between the two groups clearly established that

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VigRX Plus was superior to placebo in improving the erectile function of men. The
findings are consistent with effectiveness of Korean red ginseng in treating ED in
randomized controlled trials 13

Here, it is noteworthy to mention that the improvement of IIEF scores achieved by VigRX
Plus are at least comparable, if not equivalent to those reported by Sildenafil in an open
label study of twelve weeks 14. A mean improvement of 60.35% in erectile function with
VigRX Plus in this study is comparable with a 66% improvement noted with Sildenafil inthe open label study. Further more, in subjects treated with VigRx Plus the increase insexual desire (47%) was even higher than that reported with Sildenafil (13 %) in the same
study. Because Sildenafil and other PDE5 inhibitors do not produce but only facilitate
erections 15, the effect of VigRX Plus in improving sexual desire is of considerable worth
and may prove useful for initiation of sexual stimulation –a critical step in the sexual
response cycle of men.
Another important finding of this study was that treatment satisfaction of patients wascorroborated by partner evaluations. Female partners of VigRX Plus treated men
showed significantly higher levels (p<0.0001) of treatment satisfaction (EDITS -partner
version) than those of placebo treated men. Since partner satisfaction is considered as
one of the important determinants of sexual dysfunction, improved EDITS (patient andpartner version) scores with VigRX Plus are predictive of a potential value of VigRX Plus
as a long term ED therapy.
The beneficial effect of VigRX Plus was further confirmed as a significantly larger
proportion of men elected to continue receiving VigRX Plus after end of the study period.
Global efficacy assessment by investigator was also in favour of VigRX Plus.
VigRX Plus did not demonstrate any significant effect on the semen analysis
parameters. A possible explanation could be the small number of observations obtained
for this parameter due to socio-cultural influences. Considering the favourable effect ofVigRX Plus on the spermatogonial cells (unpublished preclinical study) further
investigation of VigRX Plus on semen parameters in an adequately sized sample isnecessitated.

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Sexual disorders in males, especially erectile dysfunction and decreased libido, haveoften been investigated for their relationship with testosterone- the male hormone.
Despite the well-established role of testosterone in enhancing libido, its exact
contribution to erections in men remains unclear16. VigRX Plus in this study showed an
improvement in erectile function scores and a concurrent increase in libido but without
any significant change in the serum testosterone levels. It could be therefore inferred
upon that effect of VigRX Plus is not due to any testosterone mediated mechanism.
Besides, the evidence of a Rho-kinase inhibiting activity in an in vitro assay as
mentioned earlier in this report, suggests a potential mechanism for this product and its
evaluation in future studies.
Safety of VigRX Plus as demonstrated in this study is desirable in the event of concernswith current pharmacological therapies. Although Sildenafil and other PDE5 inhibitors
are effective and well tolerated in the treatment of most patients with ED, patients taking
nitrate medications and /or certain alpha-blockers cannot take selected PDE5 inhibitors.
With no major adverse effects attributable to VigRX Plus in this study, and no significant
difference occurring in the tolerability of treatment between the two groups, VigRXPlus inthis study proved to be safe in subjects with sexual dysfunction.

A limitation of this study is that it excluded patients with organic causes and risk factorsof ED including vascular disease, diabetes mellitus, hypertension etc. Because mostmen with ED have an organic cause, the results of this study are not generalizable to alarger ED population. Thus evaluation of VigRx Plus in subjects with an underlying
cause of ED is warranted in further studies.
Conclusion
In conclusion, use of VigRX Plus for twelve weeks was significantly better than placebo
in improving erectile function in subjects with sexual dysfunction. It was also significantly
superior to placebo in improving the other aspects of sexual health such as libido,intercourse satisfaction, orgasmic function and overall satisfaction. The enhancement ofsexual function was endorsed by female partners of subjects receiving VigRX Plus.
VigRX Plus was safe and well tolerated in subjects with male sexual dysfunction.

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9 REFERENCES
1. Alain Gregoire ABC of sexual health BMJ. 1999 January 23; 318(7178): 245–
247.
2. Johannes CB, Kleinman KP, McKinlay JB. Journal of Urology. 2000;163(2):460463. Incidence of erectile dysfunction in men 40 to 69 years old:
longitudinal results from the Massachusetts Male Aging study
3. Segraves RT. CNS Spectr. 2003 Mar;8(3):225-9.Pharmacologic management ofsexual dysfunction: benefits and limitations
4. Leiblum SR. After sildenafil: bridging the gap between pharmacologic treatment
and satisfying sexual relationships. J Clin Psychiatry. 2002;63 Suppl 5:17-22;
discussion 23-5).
5. Peter H.C. Lim, P. Moorthy, Kenneth G.F.Benton. The Clinical Safety of Viagra.
Annals of the New York Academy of Sciences Volume 962 Issue Nitric Oxide:
Novel sections, deleterious effects, and clinical potential. Pages 378 – 388.
6. Helen V Danesh-Meyer, Leonard A Levin, Erectile dysfunction drugs and risk ofanterior ischaemic optic neuropathy: casual or causal association? Br J
Ophthalmol 2007;91:1551-1555.
7. Y. Smitasiri, P. D'Souza, J. Neal-Kababick, A. G. Schauss. The Open Natural
Products Journal 2010,pp.10-19 (10) Volume 3, ISSN:1874-8481
8. R.Rosen, A.Riley, G.Wagner, I.Osterloh, J.Kirkpatrick, A.Mishra. Theinternational index of erectile function (IIEF): a multidimensional scale forassessment of erectile dysfunction.Urology, Volume 49, Issue 6, Pages 822-830
9. Althof et al .EDITS Development of questionnaires for evaluating satisfaction withtreatments for erectile dysfunction. UROLOGY 53 (4), 1999
10. T Mostafa, International Journal of Impotence Research 20, 530-536(November/December 2008)
11. R C Rosen, J C Cappelleri and N Gendrano III The International Index of Erectile
Function (IIEF): a state-of-the-science review International Journal of Impotence
Research August 2002, Volume 14, Number 4, Pages 226-244

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12. Jacob Rajfer, MD, Thomas Magee, PhD, and Nestor Gonzalez-Cadavid, PhD
Future Strategies for Treating Erectile Dysfunction Rev Urol. 2002; 4(Suppl 3):
S48–S53
13. Dai-Ja Jang, Myeong Soo Lee, Byung-Cheul Shin,Young-Cheoul Lee, andEdzard Ernst, Br J Clin Pharmacol. 2008 October; 66(4): 444–450. Red ginseng
for treating erectile dysfunction: a systematic review
14. Leonard S. Marks, Catherine Duda, Frederick J Dorey, Maria Luz Macairan, andPaul Bryan Santos.Treatment of erectile dysfunction with Sildenafil. Urology 53(1), 1999.
15. .Culley C. Carson, MD Psychosomatic Medicine 66:664-671 (2004) Erectile
Dysfunction: Evaluation and New Treatment Options
16. Mikhail N. Does testosterone have a role in erectile function? Am J Med. 2006
May;119 (5):373-82.

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10 APPENDICES
10.1 STUDY INFORMATION
10.1.1 LIST OF CONCOMITANT MEDICATIONS PROHIBITED
Medications know to cause Male Sexual Dysfunction such as:
Antihypertensives & Diuretics:
Hydrochlorothiazide, Furosemide, Bumetanide, Methyldopa, Clonidine, Guanabenz,
Guanfacine,Verapamil, Nifedipine, Hydralazine, Enalapril, Lisinopril, Metoprolol,
Propranolol, Atenolol, Losartan,Spironolactone etc
Antidepressants, anti-anxiety drugs and antiepileptic drugs
Fluoxetine,
Sertraline,
Amitriptyline, Amoxipine,
Clomipramine,
Nortriptyline Phenelzine, Chlordiazepoxide, Clorazepate, Diazepam, Imipramine,
Lorazepam, Oxazepam, Phenytoin.
Antihistamines
Diphenhydramine, Hydroxyzine, Meclizine, Promethazine Non-steroidal
anti-inflammatory drugs
Naproxen, Indomethacin
Parkinson's disease medications
Biperiden, Benztropine, Trihexyphenidyl, Procyclidine, Bromocriptine, Levodopa
Antiarrythmics :Digoxin
Disopyramide (Norpace)
Histamine H2-receptor antagonists Cimetidine, Nizatidine OHA- Pioglitazone Antiandrogens (ketoconazole, spironolactone)

10.1.2 DEFINITION OF SERIOUS ADVERSE EVENT
A serious adverse is defined as an adverse event which:- results in death- is life threatening- requires in patient hospitalization or prolongation of hospitalization- results in permanent or persistently significant disability- is a congenital anomaly or birth defect10.1.3 IIEF QUESTIONNAIRE

Question

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Response

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Erectile function
1 How often were you able to get
an erection during sexual activity?

no sexual activity
almost never or nevera few times (much less than half the time)sometimes (about half the time)
Most times (much more than half the time)
almost always or always

0
1
2
3
4
5

2 When you had erections withsexual stimulation, how often wereyour erections hard enough forpenetration?

no sexual activity
almost never or nevera few times (much less than half the time)sometimes (about half the time)
Most times (much more than half the time)
almost always or always

0
1
2
3
4
5

3 When you attempted sexualintercourse, how often were youable to penetrate (enter) yourpartner?

did not attempt intercourse
almost never or nevera few times (much less than half the time)sometimes (about half the time)
Most times (much more than half the time)
almost always or always

0
1
2
3
4
5

4 During sexual intercourse, howoften were you able to maintainyour erection after you had
penetrated (entered) your partner?

did not attempt intercourse
almost never or nevera few times (much less than half the time)sometimes (about half the time)
Most times (much more than half the time)
almost always or always

0
1
2
3
4
5

5 During sexual intercourse, howdifficult was it to maintain yourerection to completion ofintercourse?

did not attempt intercourse
extremely difficult
very difficult
difficultslightly difficult
not difficult

0
1
2
3
4
5

very low or none at all
Low
moderateHighvery high

1
2
3
4
5

no attempts
1-2 attempts
3-4 attempts
5-6 attempts
7-10 attempts>= 11 attempts

0
1
2
3
4
5

did not attempt intercourse
almost never or never0
1

6 How do you rate your confidence
that you could get and keep an
erection?

Intercourse Satisfaction
7

How many times have you attempted
sexual intercourse?

8

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When you attempted sexualintercourse, how often was it
satisfactory for you?
9
How much have you enjoyed sexualintercourse?

08/05/2010

a few times (much less than half the time)sometimes (about half the time)
most times (much more than half the time)
almost always or always

2
3
4
5

no intercourse
no enjoyment
not very enjoyable
fairly enjoyablehighly enjoyable
very highly enjoyable

0
1
2
3
4
5

no sexual stimulation or intercourse
simulation or
almost never or0

a few times (much less than half the time)2

sometimes (about half the time)
most times (much more than half the
time)

3

almost always or always

5

no sexual stimulation or intercourse
stimulation or
almost neverhave

0

a few times (much less than half the time)2

sometimes (about half the time)
most times (much more than half the
time)

3

almost always or always

5

almost never or never1

Orgasmic Function

10 When you had sexualintercourse, how often did you
never
ejaculate?

11 When you had sexualintercourse, how often did youor neverthe feeling of orgasm or climax?

1

4

1

4

Sexual Desire

12 How often have you felt sexualdesire? a few times (much less

13 How would you rate your leveloflowsexual desire?

CONFIDENTIAL

2
than half the time)sometimes (about half the time)3

most times (much more than half the time)4

almost always or always

5very low or none at all

1
2

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moderate

3

high

4

very high5very dissatisfied
moderately dissatisfied
About equally satisfied and dissatisfied
moderately satisfied
very satisfied

1
2
3
4
5

very dissatisfied
moderately dissatisfied
About equally satisfied and dissatisfied
moderately satisfied
very satisfied

1
2
3
4
5

Overall Satisfaction
14

15

How satisfied have you been withyour overall sex life?

How satisfied have you been withyour sexual relationship with yourpartner?

10.2 TABLES REFERRED TO BUT NOT INCLUDED IN THE TEXT
10.2.1 PROTOCOL DEVIATIONS
Subject No
Dr. Gaurang Shah

Reason for deviation

DM06& DM07

IP not returned on Day 28 visit

DM10

IP not returned on Day 28 visit
Extended washout period

DM01,DM05,DM07,DM59,DM60
and DM61
DM01, DM04, DM07 and DM62

Delay in laboratory testing and Semen analysis

DM08
DM09

The subjects IP compliance calculation was 75 %when calculated at Day 84
IP not returned on Day 56 visit

DM62

IP not returned on Day 28 visit

DM03

ECG and Semen Analysis not performed
Delay in laboratory testing for Day 84 visit was bymore than 15 days

DM05
DM05
DM06

ECG and Semen analysis not performed
Laboratory testing not performed for Day 84 visit
ECG report of Day 84 is lost from the site and thus
no ECG reporting is mentioned in the CRF

DM07

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DM08
DM10

Semen Analysis not done for the subject
IP compliance as 73.80% for Day 84 visit

DM60
DM10, DM60 and DM61

IP compliance as 75.64% when calculated on Day
84 visit
Laboratory testing not performed for Day 84 visit

DM59

ECG and Semen Analysis not performed

Dr. Manoj Chaudhari

DM31
DM31
DM32

Subject enrolled in the study with out of normal
range TSH levels. Accepted Lower limit – 0.245
units. Subject value – 0.24 units.
Subject unable to give semen sample even after
repeated attempts.
Semen analysis not performed
Semen analysis not performed.

DM22, DM24, DM31, DM32,DM88
and DM47, DM57, DM67 and DM68.
Dr. Patankar
IP not returned on day 28 visit.
DM50
DM50

Delay in Laboratory evaluation

DM50

IP not returned

DM51

Delay in Laboratory evaluation

Dr. Pensalwar
DM19

IP not returned on day 28 visit

DM17, DM19, DM20, DM80, DM84

IP not returned on day 28 visit

DM15

IP not returned on day 56 visit

DM11 and DM12

Day 84 visit delayed by 12 days

DM19, DM20, DM80 and DM84.

IP not returned on day 28 visit

DM16

Subject reported 13 days early for Day 28 visit

Dr. Sable
DM036,DM037

CONFIDENTIAL

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DM042

Extended wash out period
IP not returned on day 28 visit

DM40,DM42
DM45

08/05/2010

IP not returned on day 28 visit

DM38. DM41, DM42, DM43, DM44.

Laboratory testing was not done within +3 or -3days of scheduled visit.

DM45

Laboratory testing for Day 84 visit

10.2.2 LISTING OF PATIENTS RECEIVING INVESTIGATIONAL PRODUCT
ID
DM02
DM04
DM05
DM08
DM11
DM12
DM13
DM14
DM18
DM19
DM21
DM23
DM25
DM28
DM30
DM31
DM33
DM39
DM40
DM41
DM42
DM46
DM49
DM54
DM57
DM59
DM62
DM64
DM67
DM68
DM70
DM71
DM74
DM80

CONFIDENTIAL

Initials
RDS
TSP
RSC
ASS
SMS
PMV
SAS
MFS
DNK
VBK
RCT
SNR
MMT
AMP
PKP
RRW
CKR
ADB
MUM
NBG
RBB
NMM
HPM
NJP
UAK
IFG
DBG
DGP
SSN
SDL
AKG
YVZ
PVM
JBC

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DM81
DM82
DM85
DM88
DM90

08/05/2010

SAW
SRM
MRJ
SSK
DEP

10.3 PRE-EXISTING CONDITION/CONCOMITANT MEDICATION USED IN
THE STUDY

ID
Initials
DM03 PMS

Concomitant
Medication (CM)
Paracetamol

CM Dose500 mg bd

CM Start
CM EndDate
Date
7/2/2009 10-07-2009

CM
Indication
Fever

DM06 TCV

Diclofenac gel

Twice a day

12/26/2008

BackachePentamazole

150 mg OD

10/4/2009 10-10-2009

Acidity

Tab Cetrizine

50 mg O.D.

10/9/2009 Ongoing

Cough

Tab-Paracetamol

500 mg B.D.

7/16/2009 17-07-2009

Fever

Tab-Diclofenac

100 mg9/30/2009 01-10-2009

Fever

Pentaprazole

100 mg BD

10/13/2009

22-10-2009

Acidity

Paracetamol

500 mg BD

8/18/2009 21-08-2009

Fever

Diclofenac

50 mg B.D.

8/18/2009 21-08-2009

Body pain

DM84 SRK

Pentaprazole

100 mg OD

11/1/2009 Ongoing

Acidity

DM85 MRJ

Paracetamol

500 mg8/10/2009 13-08-2009

Fever

DM10

BKG

DM11

SMS

DM17 JBCDM19

VBK

Ongoing

Note: The term ‘ongoing’ in the above table refers to pre-existing conditions

CONFIDENTIAL

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