Trial Outcomes & Findings for A Study of Tadalafil for Duchenne Muscular Dystrophy (NCT NCT01865084)

Last Updated: 2019-10-09

Results Overview

6MWD measured the distance in meters a participant was able to walk in 6 minutes. The study used 6MWD procedure modified specifically for use in boys with Duchenne muscular dystrophy (DMD), including standardized verbal encouragement at specific intervals to maintain attention to the test, and use of a "safety chaser" to walk behind the participant during testing (McDonald et al., 2010a). The LS mean (LSM) change from baseline, standard error was derived using mixed model repeated measures (MMRM) methodology with factors for pooled country, treatment, visit, treatment-by-visit interaction and baseline 6MWD as a covariate.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

331 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2019-10-09

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo taken orally once daily.	0.3 mg/kg Tadalafil 0.3 milligram per kilogram (mg/kg) tadalafil taken orally once daily.	0.6 mg/kg Tadalafil 0.6 mg/kg tadalafil taken orally once daily.
Double Blind Period (DB) STARTED	116	102	113
Double Blind Period (DB) Received at Least One Dose of Study Drug	116	102	112
Double Blind Period (DB) COMPLETED	111	98	107
Double Blind Period (DB) NOT COMPLETED	5	4	6
Open Label Extension (OLE) Period STARTED	0	150	165
Open Label Extension (OLE) Period COMPLETED	0	139	158
Open Label Extension (OLE) Period NOT COMPLETED	0	11	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo taken orally once daily.	0.3 mg/kg Tadalafil 0.3 milligram per kilogram (mg/kg) tadalafil taken orally once daily.	0.6 mg/kg Tadalafil 0.6 mg/kg tadalafil taken orally once daily.
Double Blind Period (DB) Adverse Event	2	2	1
Double Blind Period (DB) Protocol Violation	0	0	1
Double Blind Period (DB) Withdrawal by Parent/Guardian	2	2	4
Double Blind Period (DB) Withdrawal by Subject	1	0	0
Open Label Extension (OLE) Period Adverse Event	0	0	1
Open Label Extension (OLE) Period Lack of Efficacy	0	0	2
Open Label Extension (OLE) Period Lost to Follow-up	0	1	0
Open Label Extension (OLE) Period Withdrawal by Parent/Guardian	0	8	2
Open Label Extension (OLE) Period Withdrawal by Subject	0	2	2

Baseline Characteristics

A Study of Tadalafil for Duchenne Muscular Dystrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=116 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil n=102 Participants 0.3 milligram per kilogram (mg/kg) tadalafil taken orally once daily.	0.6 mg/kg Tadalafil n=113 Participants 0.6 mg/kg tadalafil taken orally once daily.	Total n=331 Participants Total of all reporting groups
Age, Continuous	9.4 years STANDARD_DEVIATION 1.76 • n=5 Participants	9.9 years STANDARD_DEVIATION 2.26 • n=7 Participants	9.5 years STANDARD_DEVIATION 1.71 • n=5 Participants	9.6 years STANDARD_DEVIATION 1.92 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	116 Participants n=5 Participants	102 Participants n=7 Participants	113 Participants n=5 Participants	331 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants	51 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	96 Participants n=5 Participants	82 Participants n=7 Participants	84 Participants n=5 Participants	262 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Argentina	7 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Russian Federation	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment United States	39 Participants n=5 Participants	34 Participants n=7 Participants	34 Participants n=5 Participants	107 Participants n=4 Participants
Region of Enrollment Japan	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Spain	9 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants	28 Participants n=4 Participants
Region of Enrollment Canada	8 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment Turkey	5 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	20 Participants n=4 Participants
Region of Enrollment Belgium	8 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Taiwan	6 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	18 Participants n=4 Participants
Region of Enrollment Korea, Republic of	3 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Italy	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment France	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Germany	8 Participants n=5 Participants	10 Participants n=7 Participants	5 Participants n=5 Participants	23 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: All randomized participants who received at least one dose of study drug who had a baseline and at least one post-baseline measurement.

Outcome measures

Outcome measures
Measure	Placebo n=113 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil n=101 Participants 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil n=111 Participants 0.6 mg/kg taken tadalafil orally once daily.
Change From Baseline in Six Minute Walk Distance (6MWD) in Meters	-50.99 Meters Standard Error 9.316	-64.71 Meters Standard Error 9.809	-59.08 Meters Standard Error 9.397

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: All randomized participants who received at least one dose of study drug who had a baseline and at least one post-baseline measurement.

The NSAA is a functional scale specifically designed for ambulant boys with DMD that can provide additional information on motor functions important in maintaining normal ambulation and other activities important to everyday life. The NSAA is a 17-item evaluation of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0, 1, or 2, with higher scores reflecting better performance on the assessment, for a total maximum score of 34. This score was transformed to a 0 to 100 scale for the key analysis (referred to as linearized), with higher transformed scores reflecting better performance.The LS mean (LSM) change from baseline standard error was derived using mixed model repeated measures methodology (MMRM) with factors for pooled country, treatment, visit, treatment-by-visit interaction and Day 1 value as baseline covariate.

Outcome measures

Outcome measures
Measure	Placebo n=116 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil n=102 Participants 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil n=112 Participants 0.6 mg/kg taken tadalafil orally once daily.
Change From Baseline in the North Star Ambulatory Assessment (NSAA) Global Score	-8.80 Units on a scale Standard Error 1.104	-9.31 Units on a scale Standard Error 1.181	-8.96 Units on a scale Standard Error 1.115

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: All randomized participants who received at least one dose of study drug who had a baseline and at least one post-baseline measurement.

Timed function tests included time it took to rise from floor, walk 10 meters, ascend 4 stairs, and descend 4 stairs.The lower the time in seconds taken, the better the performance. The LS mean change from baseline, standard error, was derived using mixed model repeated measures methodology (MMRM) with factors for pooled country, treatment, visit, treatment-by-visit interaction and Day 1 value as baseline covariate.

Outcome measures

Outcome measures
Measure	Placebo n=116 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil n=96 Participants 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil n=110 Participants 0.6 mg/kg taken tadalafil orally once daily.
Change From Baseline in Timed Function Tests in Seconds Rise from the Floor(n=92,75,89)	4.16 Seconds Standard Error 1.120	3.60 Seconds Standard Error 1.223	4.81 Seconds Standard Error 1.156
Change From Baseline in Timed Function Tests in Seconds 10 Meter Walk/Run(n=105,90,100)	1.11 Seconds Standard Error 0.204	0.95 Seconds Standard Error 0.226	1.12 Seconds Standard Error 0.217
Change From Baseline in Timed Function Tests in Seconds Stair Climb (n=116,96,110)	3.96 Seconds Standard Error 1.041	4.10 Seconds Standard Error 1.154	5.82 Seconds Standard Error 1.072
Change From Baseline in Timed Function Tests in Seconds Stair Descend(n=115,95,110)	3.19 Seconds Standard Error 0.827	2.07 Seconds Standard Error 0.915	3.27 Seconds Standard Error 0.853

SECONDARY outcome

Timeframe: Baseline through Week 48

Population: All randomized participants who received at least one dose of study drug who had complete evaluable data. Complete evaluable data was defined as having baseline measurement, complete dates at evaluable visits and a post-baseline measurement at each evaluable visit. Censored participants: placebo=71, 0.3 mg/kg=63, 0.6 mg/kg=61.

Time on study until the 6MWD becomes 10% less than the baseline 6MWD and continues at that level or lower until the end of study.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil n=101 Participants 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil n=111 Participants 0.6 mg/kg taken tadalafil orally once daily.
Time to Persistent 10% Worsening in 6MWD	NA Days These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.

SECONDARY outcome

Timeframe: Baseline through Week 48

Population: All randomized participants who received at least 1 dose of study drug who had complete evaluable data.Censored participants:Rise from Floor;placebo(pl)=40,0.3 mg/kg=39,0.6 mg/kg=43;Stair Climb;pl=55,0.3 mg/kg=45,0.6 mg/kg=52;10 Meter Walk/Run pl=61,0.3 mg/kg=65,0.6 mg/kg=58,Stair Descend;pl=63,0.3 mg/kg=60,0.6 mg/kg=59.

Time on study until the TFT becomes 10% worse than the baseline TFT and continues at that level or lower until the end of study. The time to persistent 10% worsening is the observed time after baseline until the first observed timepoint where their time used for the TFTs is \>110% of the baseline time and all the time values observed afterward are also \>110% of baseline. If the participant discontinues prior to experiencing persistent worsening, this outcome for the participant is censored at the date of discontinuation of the double-blind period. Only participants with complete evaluable data were analyzed. Complete evaluable data was defined as having baseline measurement, complete dates at evaluable visits and a post-baseline measurement at each evaluable visit.

Outcome measures

Outcome measures
Measure	Placebo n=116 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil n=102 Participants 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil n=113 Participants 0.6 mg/kg taken tadalafil orally once daily.
Time to Persistent 10% Worsening in Timed Function Tests (TFT) Rise from the Floor (n=81,67,77)	253.0 Days Interval 170.0 to These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.
Time to Persistent 10% Worsening in Timed Function Tests (TFT) Stair Climb (n=112,91,107)	255.0 Days Interval 252.0 to These statistics were not estimable due to large number of participants who were censored.	259.0 Days Interval 176.0 to These statistics were not estimable due to large number of participants who were censored.	253.0 Days Interval 185.0 to These statistics were not estimable due to large number of participants who were censored.
Time to Persistent 10% Worsening in Timed Function Tests (TFT) 10 Meter Walk/Run (n=98,83,91)	NA Days These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.
Time to Persistent 10% Worsening in Timed Function Tests (TFT) Stair Descend (n=110,91,108)	NA Days These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.	NA Days These statistics were not estimable due to large number of participants who were censored.

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: All randomized participants who received at least one dose of study drug who had a baseline and at least one post-baseline measurement. The reason the number of participants analyzed is significantly less than the total number of randomized participants is because PODCI was administered only in English.

PODCI includes a Global Functioning Scale and 5 core scales:Upper Extremity and Physical Function,Transfer/Basic Mobility, Sports/Physical Functioning, Pain/Comfort,and Happiness.The Global Functioning Scale is the mean of the mean scores from 4 of the 5 core scales (all except the happiness core scale).The following PODCI scores were prespecified in the protocol for analysis: Global Functioning, Upper Extremity and Physical Function,Transfer/Basic Mobility, and Sports/Physical Functioning. The Global Functioning Scale and each of the core scales were standardized so that a score of "0" represents a poor outcome/worse health, while "100" is the best possible outcome/best health (i.e., complete range of each score is 0 to 100, with higher scores representing better functioning). The LS mean (LSM) change from baseline,standard error was derived using MMRM with factors for pooled country, treatment, visit, treatment-by-visit interaction and baseline PODC scale as covariate.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil n=35 Participants 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil n=34 Participants 0.6 mg/kg taken tadalafil orally once daily.
Change From Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) Scores Global Functioning Scale (n=41,34,34)	-8.81 Units on a scale Standard Error 1.770	-7.36 Units on a scale Standard Error 1.929	-7.34 Units on a scale Standard Error 1.888
Change From Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) Scores Upper Extremity & Physical Function	-5.47 Units on a scale Standard Error 1.901	-3.73 Units on a scale Standard Error 2.060	-2.47 Units on a scale Standard Error 2.042
Change From Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) Scores Transfer/Basic Mobility Core Scale	-14.26 Units on a scale Standard Error 3.037	-12.50 Units on a scale Standard Error 3.260	-12.78 Units on a scale Standard Error 3.279
Change From Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) Scores Sports/Physical Functioning Core Scale	-12.47 Units on a scale Standard Error 2.362	-11.98 Units on a scale Standard Error 2.552	-7.88 Units on a scale Standard Error 2.537

SECONDARY outcome

Timeframe: Weeks 4, 12, 24 and 36: -1 Hour up to 24 Hours Postdose

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.

The data reported are population estimate and inter-patient variability.

Outcome measures

Outcome measures
Measure	Placebo n=210 Participants Placebo taken orally once daily.	0.3 mg/kg Tadalafil 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil 0.6 mg/kg taken tadalafil orally once daily.
Pharmacokinetics (PK): Apparent Clearance (CL/F) of Tadalafil	1.79 Liter per hour (L/hr) Geometric Coefficient of Variation 29.6	—	—

Adverse Events

Placebo - DB

Serious events: 5 serious events

Other events: 83 other events

Deaths: 0 deaths

0.3 mg/kg Tadalafil -DB

Serious events: 4 serious events

Other events: 82 other events

Deaths: 0 deaths

0.6 mg/kg Tadalafil - DB

Serious events: 6 serious events

Other events: 92 other events

Deaths: 0 deaths

0.3 mg/kg Tadalafil - OLE

Serious events: 6 serious events

Other events: 68 other events

Deaths: 0 deaths

0.6 mg/kg Tadalafil - OLE

Serious events: 9 serious events

Other events: 84 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo - DB n=116 participants at risk Placebo taken orally once daily.	0.3 mg/kg Tadalafil -DB n=102 participants at risk 0.3 milligram per kilogram (mg/kg) tadalafil taken orally once daily.	0.6 mg/kg Tadalafil - DB n=112 participants at risk 0.6 mg/kg tadalafil taken orally once daily.	0.3 mg/kg Tadalafil - OLE n=150 participants at risk 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil - OLE n=165 participants at risk 0.6 mg/kg tadalafil taken orally once daily.
Cardiac disorders Myocarditis	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.98% 1/102 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Gastrointestinal disorders Vomiting	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
General disorders Abasia	0.86% 1/116 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Appendicitis	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Bronchitis	0.86% 1/116 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Gastroenteritis	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Gastroenteritis viral	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Gastrointestinal infection	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.98% 1/102 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Influenza	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Pharyngotonsillitis	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.89% 1/112 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Pneumonia	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.98% 1/102 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Pneumonia adenoviral	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.89% 1/112 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Varicella	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.89% 1/112 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Injury, poisoning and procedural complications Fall	0.86% 1/116 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.8% 2/112 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Injury, poisoning and procedural complications Femoral neck fracture	0.86% 1/116 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.8% 2/112 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Injury, poisoning and procedural complications Lower limb fracture	0.86% 1/116 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Musculoskeletal and connective tissue disorders Muscle contracture	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.98% 1/102 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Musculoskeletal and connective tissue disorders Tendinous contracture	0.86% 1/116 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.89% 1/112 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Musculoskeletal and connective tissue disorders Tendon disorder	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Nervous system disorders Extrapyramidal disorder	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Psychiatric disorders Self injurious behaviour	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Psychiatric disorders Suicidal ideation	0.00% 0/116 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/102 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/112 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.

Other adverse events

Other adverse events
Measure	Placebo - DB n=116 participants at risk Placebo taken orally once daily.	0.3 mg/kg Tadalafil -DB n=102 participants at risk 0.3 milligram per kilogram (mg/kg) tadalafil taken orally once daily.	0.6 mg/kg Tadalafil - DB n=112 participants at risk 0.6 mg/kg tadalafil taken orally once daily.	0.3 mg/kg Tadalafil - OLE n=150 participants at risk 0.3 mg/kg tadalafil taken orally once daily.	0.6 mg/kg Tadalafil - OLE n=165 participants at risk 0.6 mg/kg tadalafil taken orally once daily.
Gastrointestinal disorders Abdominal pain	5.2% 6/116 • Number of events 7 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	3.9% 4/102 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	8.0% 9/112 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.3% 2/150 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.8% 3/165 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Gastrointestinal disorders Abdominal pain upper	6.0% 7/116 • Number of events 7 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.9% 5/102 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	7.1% 8/112 • Number of events 8 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.7% 4/150 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.2% 2/165 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Gastrointestinal disorders Diarrhoea	8.6% 10/116 • Number of events 10 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	5.9% 6/102 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	8.9% 10/112 • Number of events 19 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	6.0% 9/150 • Number of events 13 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.2% 7/165 • Number of events 7 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Gastrointestinal disorders Nausea	1.7% 2/116 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	6.9% 7/102 • Number of events 8 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.7% 3/112 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Gastrointestinal disorders Vomiting	12.1% 14/116 • Number of events 20 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	5.9% 6/102 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	15.2% 17/112 • Number of events 25 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	6.0% 9/150 • Number of events 12 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	6.1% 10/165 • Number of events 11 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
General disorders Abasia	5.2% 6/116 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	13.7% 14/102 • Number of events 14 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	8.0% 9/112 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	8.0% 12/150 • Number of events 12 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	9.7% 16/165 • Number of events 16 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
General disorders Pyrexia	3.4% 4/116 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	10.8% 11/102 • Number of events 11 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	8.0% 9/112 • Number of events 10 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.7% 7/150 • Number of events 8 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	3.6% 6/165 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Gastroenteritis	5.2% 6/116 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	3.9% 4/102 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.7% 3/112 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.0% 3/150 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.2% 2/165 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Influenza	7.8% 9/116 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	7.8% 8/102 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.5% 5/112 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.0% 3/150 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.2% 2/165 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Nasopharyngitis	13.8% 16/116 • Number of events 26 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	7.8% 8/102 • Number of events 10 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	16.1% 18/112 • Number of events 24 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	5.3% 8/150 • Number of events 10 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	7.3% 12/165 • Number of events 12 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Sinusitis	5.2% 6/116 • Number of events 11 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	3.9% 4/102 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.7% 3/112 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.67% 1/150 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/165 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Infections and infestations Upper respiratory tract infection	8.6% 10/116 • Number of events 18 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	9.8% 10/102 • Number of events 21 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	10.7% 12/112 • Number of events 16 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.0% 6/150 • Number of events 15 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.8% 8/165 • Number of events 10 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Injury, poisoning and procedural complications Fall	20.7% 24/116 • Number of events 41 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	17.6% 18/102 • Number of events 30 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	19.6% 22/112 • Number of events 41 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	10.7% 16/150 • Number of events 22 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	9.1% 15/165 • Number of events 18 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Musculoskeletal and connective tissue disorders Back pain	7.8% 9/116 • Number of events 15 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	10.8% 11/102 • Number of events 12 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	6.2% 7/112 • Number of events 7 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.7% 7/150 • Number of events 7 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	5.5% 9/165 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Musculoskeletal and connective tissue disorders Muscle spasms	6.0% 7/116 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.9% 3/102 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.7% 3/112 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.00% 0/150 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.2% 2/165 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 8/116 • Number of events 14 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	5.9% 6/102 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	8.9% 10/112 • Number of events 11 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.3% 2/150 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.4% 4/165 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Nervous system disorders Headache	31.0% 36/116 • Number of events 92 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	39.2% 40/102 • Number of events 57 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	38.4% 43/112 • Number of events 68 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	5.3% 8/150 • Number of events 12 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	8.5% 14/165 • Number of events 19 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Reproductive system and breast disorders Erection increased	2.6% 3/116 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	9.8% 10/102 • Number of events 11 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	15.2% 17/112 • Number of events 18 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.3% 2/150 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.4% 4/165 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Reproductive system and breast disorders Spontaneous penile erection	3.4% 4/116 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	12.7% 13/102 • Number of events 13 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	11.6% 13/112 • Number of events 14 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.0% 3/150 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.4% 4/165 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Respiratory, thoracic and mediastinal disorders Cough	8.6% 10/116 • Number of events 11 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	3.9% 4/102 • Number of events 4 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.5% 5/112 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.7% 4/150 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	3.0% 5/165 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.3% 5/116 • Number of events 11 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	9.8% 10/102 • Number of events 15 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	5.4% 6/112 • Number of events 8 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.7% 4/150 • Number of events 6 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.8% 3/165 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Skin and subcutaneous tissue disorders Rash	6.0% 7/116 • Number of events 7 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.9% 3/102 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	4.5% 5/112 • Number of events 5 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	2.0% 3/150 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	0.61% 1/165 • Number of events 1 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.
Vascular disorders Flushing	2.6% 3/116 • Number of events 3 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	7.8% 8/102 • Number of events 8 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	7.1% 8/112 • Number of events 9 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.3% 2/150 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.	1.2% 2/165 • Number of events 2 All randomized participants who received at least one dose of study drug for Placebo - DB, 0.3 mg/kg Tadalafil -DB and 0.6 mg/kg Tadalafil - DB arms during the DB period. All randomized participants who received at least one dose of study drug for 0.3 mg/kg Tadalafil - OLE and 0.6 mg/kg Tadalafil - OLE arms during the OLE period.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60