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Clinical Trial Results:
An Exploratory Study of the Safety and Efficacy of BOTOX® for the Treatment of Premature Ejaculation

Summary
EudraCT number	2013-001650-94
Trial protocol	GB
Global end of trial date	15 Aug 2017

Results information
Results version number	v1(current)
This version publication date	25 Aug 2018
First version publication date	25 Aug 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

191622-133

ISRCTN number

US NCT number

NCT01917006

WHO universal trial number (UTN)

Sponsor organisation name

Allergan

Sponsor organisation address

2525 Dupont Dr, Irvine, United States, 92612

Public contact

Clinical Trials Registry Team, Allergan, 001 877‐277‐8566, IR-CTRegistration@Allergan.com

Scientific contact

Therapeutic Area Head, Allergan, 001 714-246-4500, IR-CTRegistration@Allergan.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Aug 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Aug 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary study objectives were to explore the safety and efficacy of a range of doses of OnabotulinumtoxinA for the treatment of premature ejaculation in male participants.

Protection of trial subjects

All study participants were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Aug 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 17

Country: Number of subjects enrolled

United States: 42

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants received a single treatment of either placebo or OnabotulinumtoxinA (Doses 1, 2, 3, 4, 5. 6), delivered bilaterally to the bulbospongiosus muscle in randomized-treatment period. Participants who completed 12 weeks of randomized period were eligible to receive second injection with OnabotulinumtoxinA Dose 2 in Open-label Period.

Number of subjects started

Number of subjects completed

Reason: Number of subjects

Not Included in mITT Population: 2

Period 1 title

Randomized-treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

OnabotulinumtoxinA Dose 1

Arm description

OnabotulinumtoxinA Dose 1 injected into specified muscle per protocol on Day 1.

Arm type

Experimental

Investigational medicinal product name

BOTOX®

Investigational medicinal product code

Other name

Botulinum Toxin Type A

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of OnabotulinumtoxinA Dose 1 delivered bilaterally to the bulbospongiosus muscle (BSM).

OnabotulinumtoxinA Dose 2

Arm description

OnabotulinumtoxinA Dose 2 injected into specified muscle per protocol on Day 1. Participants were eligible for another treatment after 12 weeks.

Arm type

Experimental

Investigational medicinal product name

BOTOX®

Investigational medicinal product code

Other name

Botulinum Toxin Type A

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of OnabotulinumtoxinA Dose 2 delivered bilaterally to the BSM.

OnabotulinumtoxinA Dose 3

Arm description

OnabotulinumtoxinA Dose 3 injected into specified muscle per protocol on Day 1.

Arm type

Experimental

Investigational medicinal product name

BOTOX®

Investigational medicinal product code

Other name

Botulinum Toxin Type A

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of OnabotulinumtoxinA Dose 3 delivered bilaterally to the BSM.

OnabotulinumtoxinA Dose 4

Arm description

OnabotulinumtoxinA Dose 4 injected into specified muscle per protocol on Day 1.

Arm type

Experimental

Investigational medicinal product name

BOTOX®

Investigational medicinal product code

Other name

Botulinum Toxin Type A

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of OnabotulinumtoxinA Dose 4 U delivered bilaterally to the BSM.

OnabotulinumtoxinA Dose 5

Arm description

OnabotulinumtoxinA Dose 5 injected into specified muscle per protocol on Day 1.

Arm type

Experimental

Investigational medicinal product name

BOTOX®

Investigational medicinal product code

Other name

Botulinum Toxin Type A

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of OnabotulinumtoxinA Dose 5 delivered bilaterally to the BSM.

OnabotulinumtoxinA Dose 6

Arm description

OnabotulinumtoxinA Dose 6 injected into specified muscle per protocol on Day 1.

Arm type

Experimental

Investigational medicinal product name

BOTOX®

Investigational medicinal product code

Other name

Botulinum Toxin Type A

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of OnabotulinumtoxinA Dose 6 delivered bilaterally to the BSM.

Placebo

Arm description

Placebo (normal saline) injected into specified muscle per protocol on Day 1.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of Placebo delivered bilaterally to the BSM.

Number of subjects in period 1 ^[1]	OnabotulinumtoxinA Dose 1	OnabotulinumtoxinA Dose 2	OnabotulinumtoxinA Dose 3	OnabotulinumtoxinA Dose 4	OnabotulinumtoxinA Dose 5	OnabotulinumtoxinA Dose 6	Placebo
Started	5	7	8	7	8	7	15
Completed	3	7	8	7	8	7	14
Not completed	2	0	0	0	0	0	1
Lost to follow-up	1	-	-	-	-	-	-
Other Miscellaneous Reasons	-	-	-	-	-	-	1
Protocol deviation	1	-	-	-	-	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Baseline characteristics are based on the mITT population and excludes 2 participants.

Period 2 title

Open-label Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Open-label Period: OnabotulinumtoxinA Dose 2

Arm description

Participants who completed 12 weeks of randomized period were eligible to receive a second injection with active drug in the Open-label Period.

Arm type

Experimental

Investigational medicinal product name

BOTOX®

Investigational medicinal product code

Other name

Botulinum Toxin Type A

Pharmaceutical forms

Powder for injection

Routes of administration

Intramuscular use

Dosage and administration details

Participants received a single treatment of OnabotulinumtoxinA Dose 2 delivered bilaterally to the BSM.

Number of subjects in period 2 ^[2]	Open-label Period: OnabotulinumtoxinA Dose 2
Started	8
Completed	6
Not completed	2
Adverse Events	1
Lost to follow-up	1

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only 8 participants were enrolled in the Open-Label Period.

Baseline characteristics

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Reporting group title

OnabotulinumtoxinA Dose 1

Reporting group description

OnabotulinumtoxinA Dose 1 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 2

Reporting group description

OnabotulinumtoxinA Dose 2 injected into specified muscle per protocol on Day 1. Participants were eligible for another treatment after 12 weeks.

Reporting group title

OnabotulinumtoxinA Dose 3

Reporting group description

OnabotulinumtoxinA Dose 3 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 4

Reporting group description

OnabotulinumtoxinA Dose 4 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 5

Reporting group description

OnabotulinumtoxinA Dose 5 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 6

Reporting group description

OnabotulinumtoxinA Dose 6 injected into specified muscle per protocol on Day 1.

Reporting group title

Placebo

Reporting group description

Placebo (normal saline) injected into specified muscle per protocol on Day 1.

Reporting group values	OnabotulinumtoxinA Dose 1	OnabotulinumtoxinA Dose 2	OnabotulinumtoxinA Dose 3	OnabotulinumtoxinA Dose 4	OnabotulinumtoxinA Dose 5	OnabotulinumtoxinA Dose 6	Placebo	Total
Number of subjects	5	7	8	7	8	7	15	57
Age categorical
Units: Subjects
Adults (18-64 years)	5	7	8	7	8	7	15	57
Age Continuous
Units: years
arithmetic mean (standard deviation)	41.2 ( 10.83 )	41.9 ( 11.65 )	39.1 ( 5.62 )	39.3 ( 9.05 )	40.1 ( 6.53 )	39.9 ( 5.96 )	41.0 ( 6.08 )	-
Sex: Female, Male
Units: Subjects
Female	0	0	0	0	0	0	0	0
Male	5	7	8	7	8	7	15	57
Race/Ethnicity, Customized
Units: Subjects
Caucasian	3	4	5	5	5	6	9	37
Black	1	2	1	1	1	0	3	9
Asian	0	1	0	1	1	0	1	4
Hispanic	1	0	0	0	1	1	2	5
Other	0	0	2	0	0	0	0	2

End points

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Reporting group title

OnabotulinumtoxinA Dose 1

Reporting group description

OnabotulinumtoxinA Dose 1 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 2

Reporting group description

OnabotulinumtoxinA Dose 2 injected into specified muscle per protocol on Day 1. Participants were eligible for another treatment after 12 weeks.

Reporting group title

OnabotulinumtoxinA Dose 3

Reporting group description

OnabotulinumtoxinA Dose 3 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 4

Reporting group description

OnabotulinumtoxinA Dose 4 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 5

Reporting group description

OnabotulinumtoxinA Dose 5 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 6

Reporting group description

OnabotulinumtoxinA Dose 6 injected into specified muscle per protocol on Day 1.

Reporting group title

Placebo

Reporting group description

Placebo (normal saline) injected into specified muscle per protocol on Day 1.

Reporting group title

Open-label Period: OnabotulinumtoxinA Dose 2

Reporting group description

Participants who completed 12 weeks of randomized period were eligible to receive a second injection with active drug in the Open-label Period.

Primary: Change from Baseline in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)

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End point title

Change from Baseline in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)

End point description

IELT, the time from vaginal penetration to ejaculation, was measured by a stopwatch and was recorded in the sexual intercourse diary (SID). The Logarithm Value of the Geometric Mean of each individual participant’s IELT recorded in the SID up to each time point was calculated. The mean and standard deviation (SD) of log-transformed geometric mean IELTs are then calculated for each treatment group. An Analysis of Covariance (ANCOVA) Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate was used for analyses. A positive change from Baseline indicates improvement. The modified intent-to-treat (mITT) population included all randomized participants who received study treatment and had post-baseline intravaginal ejaculatory latency time (IELT) data available based on the dose actually received by the participant. Here, "n" is the number of participants with available data at the given time-point.

End point type

Primary

End point timeframe

Baseline (Day 1) to Week 12

End point values	OnabotulinumtoxinA Dose 1	OnabotulinumtoxinA Dose 2	OnabotulinumtoxinA Dose 3	OnabotulinumtoxinA Dose 4	OnabotulinumtoxinA Dose 5	OnabotulinumtoxinA Dose 6	Placebo
Number of subjects analysed	5	7	8	7	8	7	15
Units: seconds
arithmetic mean (standard deviation)
Baseline(n=5,6,8,7,8,7,15)	3.57 ( 0.283 )	3.50 ( 0.631 )	3.46 ( 0.371 )	3.52 ( 0.531 )	3.53 ( 0.475 )	3.54 ( 0.505 )	3.46 ( 0.610 )
Change from Baseline to Week 12(n= 5,6,8,7,8,7,15)	0.55 ( 1.037 )	0.69 ( 1.426 )	0.05 ( 0.856 )	0.30 ( 0.472 )	0.31 ( 0.525 )	0.59 ( 0.719 )	0.44 ( 0.615 )

OnabotulinumtoxinA Dose 1 versus (vs) Placebo

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.393 ^[1]

Method

ANCOVA

Confidence interval

Notes
[1] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from analysis of covariance (ANCOVA) Model with treatment as fixed effect and baseline geometric mean IELT as covariate.

OnabotulinumtoxinA Dose 2 vs Placebo

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.263 ^[2]

Method

ANCOVA

Confidence interval

Notes
[2] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.861 ^[3]

Method

ANCOVA

Confidence interval

Notes
[3] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.647 ^[4]

Method

ANCOVA

Confidence interval

Notes
[4] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.645 ^[5]

Method

ANCOVA

Confidence interval

Notes
[5] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.343 ^[6]

Method

ANCOVA

Confidence interval

Notes
[6] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

Secondary: Change from Baseline in Average IELT

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End point title

Change from Baseline in Average IELT

End point description

IELT, the time from vaginal penetration to ejaculation, was measured by a stopwatch and was recorded in the SID. The average of each individual participant’s IELT recorded in the SID up to each time point was calculated. The mean and SD of average IELTs were then calculated for each treatment group. An ANCOVA Model with treatment as the fixed effect and baseline average mean IELT as the covariate was used for analyses. A positive change from Baseline indicates improvement. The mITT population included all randomized participants who received study treatment and had post-baseline IELT data available based on the dose actually received by the participants. Here "n" is the number of participants with available data at the given time-point.

End point type

Secondary

End point timeframe

Baseline (Day 1) to Weeks 2, 4, 6, 8, 10, and 12

End point values	OnabotulinumtoxinA Dose 1	OnabotulinumtoxinA Dose 2	OnabotulinumtoxinA Dose 3	OnabotulinumtoxinA Dose 4	OnabotulinumtoxinA Dose 5	OnabotulinumtoxinA Dose 6	Placebo
Number of subjects analysed	5	7	8	7	8	7	15
Units: seconds
arithmetic mean (standard deviation)
Baseline(n=5,6,8,7,8,7,15)	37.25 ( 10.518 )	39.42 ( 21.504 )	34.41 ( 10.194 )	38.00 ( 16.008 )	40.88 ( 16.435 )	38.75 ( 15.596 )	37.92 ( 16.656 )
Change from Baseline to Week 2(n=5,6,8,7,8,7,14)	66.25 ( 101.132 )	180.31 ( 317.657 )	24.73 ( 59.725 )	34.87 ( 74.842 )	28.04 ( 31.298 )	55.77 ( 65.549 )	11.25 ( 23.985 )
Change from Baseline to Week 4(n=5,6,8,7,8,7,14)	61.94 ( 100.446 )	176.71 ( 367.665 )	24.06 ( 59.472 )	35.00 ( 73.475 )	28.46 ( 36.881 )	64.97 ( 67.471 )	29.30 ( 69.073 )
Change from Baseline to Week 6(n=5,6,8,7,8,7,14)	61.42 ( 100.446 )	183.44 ( 374.404 )	20.75 ( 55.850 )	36.95 ( 71.996 )	29.35 ( 39.334 )	64.49 ( 66.546 )	47.62 ( 89.847 )
Change from Baseline to Week 8(n=5,6,8,7,8,7,14)	59.55 ( 100.896 )	176.59 ( 349.777 )	17.08 ( 44.158 )	37.69 ( 71.873 )	29.48 ( 44.505 )	65.19 ( 65.612 )	65.57 ( 128.470 )
Change from Baseline to Week 10(n=5,6,8,7,8,7,15)	56.13 ( 101.447 )	170.65 ( 331.039 )	15.55 ( 39.149 )	37.45 ( 71.782 )	27.49 ( 45.365 )	63.91 ( 67.725 )	68.26 ( 146.330 )
Change from Baseline to Week 12(n=5,6,8,7,8,7,15)	53.65 ( 102.527 )	152.74 ( 295.219 )	12.95 ( 30.930 )	28.32 ( 48.965 )	27.51 ( 48.720 )	66.01 ( 71.489 )	68.49 ( 151.680 )

OnabotulinumtoxinA Dose 1 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.184 ^[7]

Method

ANCOVA

Confidence interval

Notes
[7] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[8]

Method

ANCOVA

Confidence interval

Notes
[8] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.404 ^[9]

Method

ANCOVA

Confidence interval

Notes
[9] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.328 ^[10]

Method

ANCOVA

Confidence interval

Notes
[10] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.362 ^[11]

Method

ANCOVA

Confidence interval

Notes
[11] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.203 ^[12]

Method

ANCOVA

Confidence interval

Notes
[12] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.322 ^[13]

Method

ANCOVA

Confidence interval

Notes
[13] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015 ^[14]

Method

ANCOVA

Confidence interval

Notes
[14] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.541 ^[15]

Method

ANCOVA

Confidence interval

Notes
[15] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.459 ^[16]

Method

ANCOVA

Confidence interval

Notes
[16] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.491 ^[17]

Method

ANCOVA

Confidence interval

Notes
[17] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.281 ^[18]

Method

ANCOVA

Confidence interval

Notes
[18] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.424 ^[19]

Method

ANCOVA

Confidence interval

Notes
[19] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026 ^[20]

Method

ANCOVA

Confidence interval

Notes
[20] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.67 ^[21]

Method

ANCOVA

Confidence interval

Notes
[21] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.561 ^[22]

Method

ANCOVA

Confidence interval

Notes
[22] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.604 ^[23]

Method

ANCOVA

Confidence interval

Notes
[23] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.394 ^[24]

Method

ANCOVA

Confidence interval

Notes
[24] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.532 ^[25]

Method

ANCOVA

Confidence interval

Notes
[25] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.058 ^[26]

Method

ANCOVA

Confidence interval

Notes
[26] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.778 ^[27]

Method

ANCOVA

Confidence interval

Notes
[27] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.662 ^[28]

Method

ANCOVA

Confidence interval

Notes
[28] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.712 ^[29]

Method

ANCOVA

Confidence interval

Notes
[29] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.501 ^[30]

Method

ANCOVA

Confidence interval

Notes
[30] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.565 ^[31]

Method

ANCOVA

Confidence interval

Notes
[31] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.071 ^[32]

Method

ANCOVA

Confidence interval

Notes
[32] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.799 ^[33]

Method

ANCOVA

Confidence interval

Notes
[33] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.681 ^[34]

Method

ANCOVA

Confidence interval

Notes
[34] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.741 ^[35]

Method

ANCOVA

Confidence interval

Notes
[35] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.526 ^[36]

Method

ANCOVA

Confidence interval

Notes
[36] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 12

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.584 ^[37]

Method

ANCOVA

Confidence interval

Notes
[37] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 12

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.101 ^[38]

Method

ANCOVA

Confidence interval

Notes
[38] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 12

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.823 ^[39]

Method

ANCOVA

Confidence interval

Notes
[39] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 12

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.741 ^[40]

Method

ANCOVA

Confidence interval

Notes
[40] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 12

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.756 ^[41]

Method

ANCOVA

Confidence interval

Notes
[41] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 12

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.517 ^[42]

Method

ANCOVA

Confidence interval

Notes
[42] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline average IELT as the covariate.

Secondary: Change from Baseline in Geometric Mean IELT

Top of page

End point title

Change from Baseline in Geometric Mean IELT

End point description

IELT, the time from vaginal penetration to ejaculation, was measured by a stopwatch and was recorded in the SID. The Logarithm Value of the Geometric Mean of each individual participant’s IELT recorded in the SID up to each time point was calculated. The mean and SD of log-transformed geometric mean IELTs were then calculated for each treatment group. An ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate was used for analyses. A positive change from Baseline indicates improvement. The mITT population included all randomized participants who received study treatment and had post-baseline IELT data available based on the dose actually received by the participant. Here "n" is the number of participants with available data at the given time-point.

End point type

Secondary

End point timeframe

Baseline (Day 1) to Weeks 2, 4, 6, 8, and 10

End point values	OnabotulinumtoxinA Dose 1	OnabotulinumtoxinA Dose 2	OnabotulinumtoxinA Dose 3	OnabotulinumtoxinA Dose 4	OnabotulinumtoxinA Dose 5	OnabotulinumtoxinA Dose 6	Placebo
Number of subjects analysed	5	7	8	7	8	7	15
Units: seconds
arithmetic mean (standard deviation)
Baseline(n=5,6,8,7,8,7,15)	3.57 ( 0.283 )	3.50 ( 0.631 )	3.46 ( 0.371 )	3.52 ( 0.531 )	3.53 ( 0.475 )	3.54 ( 0.505 )	3.46 ( 0.610 )
Change at Week 2(n=5,6,8,7,8,7,14)	0.76 ( 1.014 )	0.95 ( 1.497 )	0.26 ( 0.677 )	0.34 ( 0.690 )	0.47 ( 0.604 )	0.62 ( 0.623 )	0.19 ( 0.486 )
Change at Week 4(n=5,6,8,7,8,7,14)	0.70 ( 1.000 )	0.77 ( 1.505 )	0.18 ( 0.879 )	0.33 ( 0.616 )	0.38 ( 0.481 )	0.61 ( 0.618 )	0.22 ( 0.627 )
Change at Week 6(n=5,6,8,7,8,7,14)	0.70 ( 0.999 )	0.83 ( 1.513 )	0.08 ( 0.971 )	0.36 ( 0.629 )	0.36 ( 0.483 )	0.59 ( 0.722 )	0.36 ( 0.524 )
Change at Week 8(n=5,6,8,7,8,7,14)	0.67 ( 1.007 )	0.79 ( 1.525 )	0.05 ( 0.968 )	0.37 ( 0.627 )	0.36 ( 0.522 )	0.61 ( 0.682 )	0.44 ( 0.567 )
Change at Week 10(n=5,6,8,7,8,7,15)	0.60 ( 1.009 )	0.80 ( 1.503 )	0.07 ( 0.905 )	0.37 ( 0.624 )	0.32 ( 0.512 )	0.56 ( 0.727 )	0.44 ( 0.603 )

OnabotulinumtoxinA Dose 1 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.079 ^[43]

Method

ANCOVA

Confidence interval

Notes
[43] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.025 ^[44]

Method

ANCOVA

Confidence interval

Notes
[44] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.417 ^[45]

Method

ANCOVA

Confidence interval

Notes
[45] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.33 ^[46]

Method

ANCOVA

Confidence interval

Notes
[46] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.199 ^[47]

Method

ANCOVA

Confidence interval

Notes
[47] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 2

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.113 ^[48]

Method

ANCOVA

Confidence interval

Notes
[48] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.127 ^[49]

Method

ANCOVA

Confidence interval

Notes
[49] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.087 ^[50]

Method

ANCOVA

Confidence interval

Notes
[50] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.543 ^[51]

Method

ANCOVA

Confidence interval

Notes
[51] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.377 ^[52]

Method

ANCOVA

Confidence interval

Notes
[52] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.321 ^[53]

Method

ANCOVA

Confidence interval

Notes
[53] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 4

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.149 ^[54]

Method

ANCOVA

Confidence interval

Notes
[54] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.215 ^[55]

Method

ANCOVA

Confidence interval

Notes
[55] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.126 ^[56]

Method

ANCOVA

Confidence interval

Notes
[56] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.774 ^[57]

Method

ANCOVA

Confidence interval

Notes
[57] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.495 ^[58]

Method

ANCOVA

Confidence interval

Notes
[58] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.495 ^[59]

Method

ANCOVA

Confidence interval

Notes
[59] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 6

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.274 ^[60]

Method

ANCOVA

Confidence interval

Notes
[60] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.308 ^[61]

Method

ANCOVA

Confidence interval

Notes
[61] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.205 ^[62]

Method

ANCOVA

Confidence interval

Notes
[62] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.849 ^[63]

Method

ANCOVA

Confidence interval

Notes
[63] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.571 ^[64]

Method

ANCOVA

Confidence interval

Notes
[64] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.592 ^[65]

Method

ANCOVA

Confidence interval

Notes
[65] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 8

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.34 ^[66]

Method

ANCOVA

Confidence interval

Notes
[66] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 1 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 1 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.36 ^[67]

Method

ANCOVA

Confidence interval

Notes
[67] - A one-sided p-value of mean difference vs placebo for each active BOTOX dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 2 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.192 ^[68]

Method

ANCOVA

Confidence interval

Notes
[68] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 3 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 3 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.843 ^[69]

Method

ANCOVA

Confidence interval

Notes
[69] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 4 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 4 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.572 ^[70]

Method

ANCOVA

Confidence interval

Notes
[70] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 5 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 5 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.628 ^[71]

Method

ANCOVA

Confidence interval

Notes
[71] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

OnabotulinumtoxinA Dose 6 vs Placebo at Week 10

Comparison groups

OnabotulinumtoxinA Dose 6 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.38 ^[72]

Method

ANCOVA

Confidence interval

Notes
[72] - A one-sided p-value of mean difference vs placebo for each active OnabotulinumtoxinA dose level is calculated from the ANCOVA Model with treatment as the fixed effect and baseline geometric mean IELT as the covariate.

Adverse events

Top of page

Timeframe for reporting adverse events

First dose and for at least 28 days after the last dose of study medication (Up to 26 Weeks in the Randomized-treatment Period and Up to 17 Weeks in the Open-Label Period)

Adverse event reporting additional description

A treatment-emergent adverse event (TEAE) was an adverse event with onset on or after the initiation of study treatment or an adverse event with onset prior to study treatment that worsened in severity or became serious after the initiation of study treatment. Safety Population included all treated participants.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

OnabotulinumtoxinA Dose 1

Reporting group description

OnabotulinumtoxinA Dose 1 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 2

Reporting group description

OnabotulinumtoxinA Dose 2 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 3

Reporting group description

OnabotulinumtoxinA Dose 3 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 4

Reporting group description

OnabotulinumtoxinA Dose 4 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 6

Reporting group description

OnabotulinumtoxinA Dose 6 injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 5

Reporting group description

OnabotulinumtoxinA Dose 5 injected into specified muscle per protocol on Day 1.

Reporting group title

Placebo

Reporting group description

Placebo (normal saline) injected into specified muscle per protocol on Day 1.

Reporting group title

OnabotulinumtoxinA Dose 2 (Open-label Period)

Reporting group description

Participants who completed 12 weeks of randomized period were eligible to receive a second injection with active drug in the Open-label Period.

Serious adverse events	OnabotulinumtoxinA Dose 1	OnabotulinumtoxinA Dose 2	OnabotulinumtoxinA Dose 3	OnabotulinumtoxinA Dose 4	OnabotulinumtoxinA Dose 6	OnabotulinumtoxinA Dose 5	Placebo	OnabotulinumtoxinA Dose 2 (Open-label Period)
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	OnabotulinumtoxinA Dose 1	OnabotulinumtoxinA Dose 2	OnabotulinumtoxinA Dose 3	OnabotulinumtoxinA Dose 4	OnabotulinumtoxinA Dose 6	OnabotulinumtoxinA Dose 5	Placebo	OnabotulinumtoxinA Dose 2 (Open-label Period)
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 5 (60.00%)	2 / 7 (28.57%)	1 / 8 (12.50%)	2 / 8 (25.00%)	4 / 8 (50.00%)	3 / 8 (37.50%)	12 / 15 (80.00%)	3 / 8 (37.50%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	1	1	0
Chills
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Injection site paraesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Injection site pruritus
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Reproductive system and breast disorders
Ejaculation disorder
subjects affected / exposed	3 / 5 (60.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	2 / 15 (13.33%)	0 / 8 (0.00%)
occurrences all number	6	0	0	0	0	0	3	0
Epididymal tenderness
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Perineal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Pruritus genital
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 15 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	1	0	1
Erectile dysfunction
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Ejaculation failure
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Sinus congestion
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Cough
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Dyspnoea
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Psychiatric disorders
Enuresis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Psychogenic erectile dysfunction
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Investigations
Semen volume decreased
subjects affected / exposed	2 / 5 (40.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	2 / 15 (13.33%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	2	0
Heart rate irregular
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Injury, poisoning and procedural complications
Joint injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Penis injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Concussion
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Contusion
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Road traffic accident
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	3 / 15 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	4	0
Dizziness
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Loss of consciousness
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Memory impairment
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Eye disorders
Vision blurred
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0
Abdominal pain lower
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Constipation
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Abnormal faeces
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Diarrhoea
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Dyshidrotic eczema
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Skin odour abnormal
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0
Rosacea
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	1
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Terminal dribbling
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Urine odour abnormal
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Endocrine disorders
Hypogonadism
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	1
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	2	0
Muscle spasms
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	3 / 15 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0
Arthralgia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Infections and infestations
Influenza
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	3 / 15 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	3	0
Pharyngitis streptococcal
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Sinusitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Ear infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Gastroenteritis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 15 (6.67%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Gastroenteritis viral
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

21 Apr 2015

Amendment 1 • The first amendment of the protocol was implemented prior to enrollment for Cohort 5 • This amendment incorporated collection and analysis for an additional exploratory efficacy endpoint • Using an ultrasound, various measurements of participants bulbospongiosus muscle (BSM) were taken prior to treatment and at the Week 4 visit • The statistical analysis plan (SAP) was amended to include an analysis of these measurements, which was descriptive in nature • The collection and analysis of the BSM were only undertaken with participants in Cohort 5 and subsequently excluded in Amendment 2 • Additionally, after the Data Review Committee’s (DRC’s) review of safety data from the first 6 participants in Cohort 5, it was decided to reduce the dosage for subsequent participants enrolled into the active treatment arm of Cohort 5. The active dose was reduced from OnabotulinumtoxinA Dose 1 down to OnabotulinumtoxinA Dose 2. Since authority to do so was granted to the DRC in both the original study protocol as well as DRC charter, a protocol amendment was not required • Other than inclusion of an additional treatment arm, this decision implied no material change to the planned statistical analysis. Consequently, a SAP amendment was not needed.

15 Jul 2016

Amendment 2 • The second amendment to the protocol occurred prior to the start of Cohort 6 • This amendment stipulated an increase in the number of participants enrolled into Cohort 6 from 10 to 24 as well as changing the dosage of the active treatment from OnabotulinumtoxinA Dose A to OnabotulinumtoxinA Dose 2 • Additionally, participants in Cohort 6 had the option to enter a 12-week open-label extension period • As mentioned earlier, the BSM measurements included in Amendment 1 were removed for Amendment 2 • The SAP was amended to incorporate analysis for the open-label period that was descriptive in nature.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
01 Feb 2015	The study was on an enrollment hold due to a major protocol amendment and adding the Dose 2 dose. The hold was not mandated by Food and Drug Administration (FDA), but was necessary to program our interactive web response system (IWRS) and Electronic Data Capture (EDC) systems to account for the major changes. The hold went from Sept 2015 to May of 2016.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
An Exploratory Study of the Safety and Efficacy of BOTOX® for the Treatment of Premature Ejaculation

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)

Primary: Change from Baseline in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)

Secondary: Change from Baseline in Average IELT

Secondary: Change from Baseline in Average IELT

Secondary: Change from Baseline in Geometric Mean IELT

Secondary: Change from Baseline in Geometric Mean IELT

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: An Exploratory Study of the Safety and Efficacy of BOTOX® for the Treatment of Premature Ejaculation

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)

Primary: Change from Baseline in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)

Secondary: Change from Baseline in Average IELT

Secondary: Change from Baseline in Average IELT

Secondary: Change from Baseline in Geometric Mean IELT

Secondary: Change from Baseline in Geometric Mean IELT

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Exploratory Study of the Safety and Efficacy of BOTOX® for the Treatment of Premature Ejaculation