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Study the Safety and Effectiveness of Tadalafil on High Blood Pressure in the Blood Vessel Going From the Heart to the Lungs

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00549302
Collaborator
ICOS Corporation (Industry)
357
Enrollment
10
Locations
2
Arms
74
Duration (Months)
35.7
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study to determine the long term safety of tadalafil in patients with increased blood pressure in the blood vessel that carries blood from the right heart to the lungs and to see if it will keep the disease from getting worse.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
357 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
An Extension Study to Evaluate the Long-Term Safety and Efficacy of the Phosphodiesterase Type 5 (PDE5) Inhibitor Tadalafil in the Treatment of Patients With Pulmonary Arterial Hypertension
Study Start Date :
Dec 1, 2005
Actual Primary Completion Date :
Feb 1, 2012
Actual Study Completion Date :
Feb 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 20 mg tadalafil

20 milligram (mg) tadalafil taken once a day

Drug: tadalafil
20 milligram (mg) tablet, taken by mouth once a day for 52 weeks for the phase 1 portion. Open label phase includes 40 mg tablet taken by mouth once a day until the sponsor concludes the study or tadalafil becomes commercially available for the treatment of Pulmonary Arterial Hypertension (PAH).
Other Names:
  • LY450190
  • Cialis
  • IC351

    		•
    Active Comparator: 40 mg tadalafil

    40 mg tadalafil tablet taken once a day

    Drug: tadalafil
    40 mg tablet taken by mouth once a day for 52 weeks in phase 1. Open label phase includes 40 mg tablet taken by mouth once a day until the sponsor concludes the study or tadalafil becomes commercially available for the treatment of PAH.
    Other Names:
  • LY450190
  • Cialis
  • IC351

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) [Baseline (Double-Blind Period) up to Week 243 (End of Open-Label Period)]

      A summary of serious and all other non-serious AEs, which include adverse events reported for laboratory tests and vital signs, is located in the Reported Adverse Event module.

    Secondary Outcome Measures

    1. 6-Minute Walk Distance (6MWD) at Baseline and Weeks 16, 28, 40 and 52 [Baseline and Weeks 16, 28, 40 and 52]

      6MWD measured the distance a participant was able to walk unassisted in 6 minutes.

    2. Borg Dyspnea Assessment at Baseline and Weeks 16, 28, 40 and 52 [Baseline and Weeks 16, 28, 40 and 52]

      Borg dyspnea score is a participant rated measure of their greatest degree of shortness of breath during exertion (6-minute walk test). Score ranged from 0 (nothing at all) to 10 (very, very severe [maximal]).

    3. Probability of No Pulmonary Arterial Hypertension (PAH) Deterioration at Weeks 16, 28, 40 and up to 52 [Baseline and Weeks 16, 28, 40 and 52]

      World Health Organization Functional Classification Assessment (WHO FC) is a method of classifying disease severity in PAH. The classes are: Class I: pulmonary hypertension (PH) but without resulting limitation of physical activity, Class II: PH resulting in slight limitation of physical activity, Class III: PH resulting in marked limitation of physical activity, Class IV: PH with inability to carry out any physical activity without symptoms. Deterioration of WHO FC is defined as moving to a higher WHO FC within one visit. Results are presented as Kaplan-Meier estimates (% probability) of remaining free from WHO FC deterioration after a given time.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Must have participated and discontinued in the previous PAH placebo controlled study due to clinical worsening on placebo or tadalafil 2.5 mg, 10mg, or 20 mg

    • Must have completed Week 16 of the previous PAH study and had either no clinical worsening or became clinically worse at the Week 16 visit on placebo or tadalafil 2.5 mg, 10mg, or 20 mg

    • Females who have a negative urine pregnancy test and are willing to use 2 types of birth control

    • Be 12 years or older (country specific regulations apply) with parental approval

    Exclusion Criteria:

    • Participated in the placebo controlled study and had clinical worsening on 40 mg tadalafil

    • Have left-sided heart disease

    • Have a musculoskeletal disorder that limits being able to get around

    • Nitrate use

    • Certain current systemic treatments

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Bend Oregon United States 97701
    2 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Brussels Belgium
    3 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Toronto Ontario Canada
    4 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lille France
    5 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Berlin Germany
    6 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Dublin Ireland
    7 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Bergamo Italy
    8 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Tokyo Japan
    9 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Barcelona Spain
    10 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon- Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. London United Kingdom

    Sponsors and Collaborators

    • Eli Lilly and Company
    • ICOS Corporation

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00549302
    Other Study ID Numbers:
    • 10263
    • H6D-MC-LVGX
    First Posted:
    Oct 25, 2007
    Last Update Posted:
    Apr 9, 2013
    Last Verified:
    Apr 1, 2013
    Additional relevant MeSH terms:
    Hypertension, Pulmonary
    Hypertension
    Tadalafil

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participants were previously enrolled in H6D-MC-LVGY (NCT00125918), a placebo-controlled double-blind study.
    Arm/Group Title Tadalafil 20 mg Double Blind Tadalafil 40 mg Double-Blind Tadalafil 40 mg Open-Label
    Arm/Group Description Tadalafil, 20 milligram (mg) administered orally as 1 tadalafil tablet and 1 matched placebo tablet once daily from Day 1 up to 52 weeks of treatment. Tadalafil, 40 mg (two 20 mg tablets) administered orally once daily from Day 1 up to 52 weeks of treatment. Tadalafil, 40 mg (two 20 mg tablets) administered orally once daily from Week 53 up to Week 243.
    Period Title: Double-Blind
    STARTED 63 294 0
    Received at Least One Dose of Study Drug 63 294 0
    COMPLETED 52 241 0
    NOT COMPLETED 11 53 0
    Period Title: Double-Blind
    STARTED 0 0 286
    COMPLETED 0 0 217
    NOT COMPLETED 0 0 69

    Baseline Characteristics

    Arm/Group Title Tadalafil 20 Milligrams (mg) Double-Blind Tadalafil 40 mg Double-Blind Total
    Arm/Group Description Tadalafil, 20 milligram (mg) administered orally as 1 tadalafil tablet and 1 matched placebo tablet once daily from Day 1 up to 52 weeks of treatment. Tadalafil, 40 mg (two 20 mg tablets) administered orally once daily from Day 1 up to 52 weeks of treatment. Total of all reporting groups
    Overall Participants 63 294 357
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53.04
    (15.58)
    53.94
    (15.36)
    53.78
    (15.38)
    Sex: Female, Male (Count of Participants)
    Female
    48
    76.2%
    230
    78.2%
    278
    77.9%
    Male
    15
    23.8%
    64
    21.8%
    79
    22.1%
    Region of Enrollment (participants) [Number]
    Belgium
    2
    3.2%
    5
    1.7%
    7
    2%
    Canada
    4
    6.3%
    38
    12.9%
    42
    11.8%
    France
    3
    4.8%
    22
    7.5%
    25
    7%
    Germany
    6
    9.5%
    34
    11.6%
    40
    11.2%
    Ireland
    0
    0%
    1
    0.3%
    1
    0.3%
    Italy
    4
    6.3%
    25
    8.5%
    29
    8.1%
    Japan
    5
    7.9%
    17
    5.8%
    22
    6.2%
    Spain
    2
    3.2%
    4
    1.4%
    6
    1.7%
    United States
    33
    52.4%
    139
    47.3%
    172
    48.2%
    United Kingdom
    4
    6.3%
    9
    3.1%
    13
    3.6%
    Race (participants) [Number]
    White
    48
    76.2%
    243
    82.7%
    291
    81.5%
    Asian
    7
    11.1%
    22
    7.5%
    29
    8.1%
    Black or African American
    5
    7.9%
    23
    7.8%
    28
    7.8%
    American Indian or Alaska Native
    2
    3.2%
    3
    1%
    5
    1.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    2
    0.7%
    2
    0.6%
    American Indian or Alaska Native/White
    0
    0%
    1
    0.3%
    1
    0.3%
    Black or African American/Native Hawaiian or Other
    1
    1.6%
    0
    0%
    1
    0.3%
    Weight (kilograms (kg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms (kg)]
    73.92
    (18.90)
    75.26
    (19.80)
    75.02
    (19.63)
    Ethnicity (participants) [Number]
    Hispanic or Latino
    4
    6.3%
    36
    12.2%
    40
    11.2%
    Not Hispanic or Latino
    59
    93.7%
    258
    87.8%
    317
    88.8%
    Etiology (participants) [Number]
    Idiopathic
    37
    58.7%
    186
    63.3%
    223
    62.5%
    Related to Collagen Vascular Disease
    16
    25.4%
    62
    21.1%
    78
    21.8%
    Associated with Atrial Septal Defect
    3
    4.8%
    26
    8.8%
    29
    8.1%
    Related to Anorexigen Use
    4
    6.3%
    11
    3.7%
    15
    4.2%
    Surgical Repair, of at least 1 Year Duration
    3
    4.8%
    9
    3.1%
    12
    3.4%
    Current Bosentan Use (participants) [Number]
    Yes
    37
    58.7%
    155
    52.7%
    192
    53.8%
    No
    26
    41.3%
    139
    47.3%
    165
    46.2%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description A summary of serious and all other non-serious AEs, which include adverse events reported for laboratory tests and vital signs, is located in the Reported Adverse Event module.
    Time Frame Baseline (Double-Blind Period) up to Week 243 (End of Open-Label Period)

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Tadalafil 20 mg or 40 mg Double-Blind and 40 mg Open-Label
    Arm/Group Description Tadalafil 20 mg tablets administered orally as one tablet tadalafil and one tablet matched placebo once per day from Day 1 up to 52 weeks of treatment or tadalafil, two 20 mg tablets (40 mg total) administered orally once per day from Day 1 up to 52 weeks of treatment in Double-blind period; and tadalafil, two 20 mg tablets (40 mg total) administered orally once per day from Week 53 up to Week 243 in Open-label period.
    Measure Participants 357
    Serious AEs
    184
    292.1%
    Other Non-Serious AEs
    334
    530.2%
    2. Secondary Outcome
    Title 6-Minute Walk Distance (6MWD) at Baseline and Weeks 16, 28, 40 and 52
    Description 6MWD measured the distance a participant was able to walk unassisted in 6 minutes.
    Time Frame Baseline and Weeks 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and who completed 6MWD test; Last Observation Carried Forward (LOCF)
    Arm/Group Title Tadalafil 20 Milligrams (mg) Double-Blind Tadalafil 40 mg Double-Blind
    Arm/Group Description Tadalafil, 20 milligram (mg) administered orally as 1 tadalafil tablet and 1 matched placebo tablet once daily from Day 1 up to 52 weeks of treatment. Tadalafil, 40 mg (two 20 mg tablets) administered orally once daily from Day 1 up to 52 weeks of treatment.
    Measure Participants 63 284
    Distance walked at Baseline (n=63, 287
    397.74
    (71.74)
    375.38
    (93.41)
    Distance walked at Week 16 (n=58, 272)
    396.37
    (77.01)
    381.47
    (96.86)
    Distance walked at Week 28 (n=55, 250)
    406.41
    (106.76)
    384.97
    (95.03)
    Distance walked at Week 40 (n=51, 241)
    411.81
    (78.72)
    386.57
    (94.04)
    Distance walked at Week 52 (n=51, 235)
    415.31
    (79.82)
    394.00
    (91.56)
    Endpoint-Week 52 or LOCF (n=60,281)
    401.52
    (90.29)
    379.80
    (99.12)
    3. Secondary Outcome
    Title Borg Dyspnea Assessment at Baseline and Weeks 16, 28, 40 and 52
    Description Borg dyspnea score is a participant rated measure of their greatest degree of shortness of breath during exertion (6-minute walk test). Score ranged from 0 (nothing at all) to 10 (very, very severe [maximal]).
    Time Frame Baseline and Weeks 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and who completed the Borg Dyspnea Assessment; LOCF
    Arm/Group Title Tadalalfil 20 Milligrams (mg) Tadalafil 40 mg
    Arm/Group Description Tadalafil, 20 milligram (mg) tablets administered orally as one tablet tadalafil and one tablet matched placebo once per day from Day 1 up to 52 weeks of treatment; LOCF. Tadalafil, two 20 mg tablets (40 mg total) administered orally once per day from Day 1 up to 52 weeks of treatment.
    Measure Participants 63 294
    Score at Baseline (n=62, 287)
    3.41
    (2.38)
    3.65
    (2.43)
    Score at Week 16 (n=58, 271)
    3.41
    (2.48)
    3.51
    (2.35)
    Score at Week 28 (n=54,249)
    3.46
    (2.40)
    3.44
    (2.21)
    Score at Week 40 (n=51, 240)
    3.21
    (2.43)
    3.38
    (2.27)
    Score at Week 52 (n=51,235)
    3.68
    (2.43)
    3.29
    (2.16)
    Endpoint-Week 52 or LOCF (n=60,281)
    3.75
    (2.34)
    3.54
    (2.36)
    4. Secondary Outcome
    Title Probability of No Pulmonary Arterial Hypertension (PAH) Deterioration at Weeks 16, 28, 40 and up to 52
    Description World Health Organization Functional Classification Assessment (WHO FC) is a method of classifying disease severity in PAH. The classes are: Class I: pulmonary hypertension (PH) but without resulting limitation of physical activity, Class II: PH resulting in slight limitation of physical activity, Class III: PH resulting in marked limitation of physical activity, Class IV: PH with inability to carry out any physical activity without symptoms. Deterioration of WHO FC is defined as moving to a higher WHO FC within one visit. Results are presented as Kaplan-Meier estimates (% probability) of remaining free from WHO FC deterioration after a given time.
    Time Frame Baseline and Weeks 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Tadalafil 20 Milligrams (mg) Double-Blind Tadalafil 40 mg Double-Blind
    Arm/Group Description Tadalafil, 20 milligram (mg) administered orally as 1 tadalafil tablet and 1 matched placebo tablet once daily from Day 1 up to 52 weeks of treatment. Tadalafil, 40 mg (two 20 mg tablets) administered orally once daily from Day 1 up to 52 weeks of treatment.
    Measure Participants 63 294
    Week 16 (n=57, 262)
    95
    96
    Week 28 (n=50, 238)
    88
    90
    Week 40 (n=45, 222)
    81
    88
    Week 52 (n=33,136)
    81
    85

    Adverse Events

    Time Frame
    Adverse Event Reporting Description All treatment emergent adverse events (TEAEs) defined as a Serious Adverse Event (SAEs) and Other Non-serious Adverse Event (AEs) which were either first reported or worsened in severity during the Double-Blind Period or the Open-Label Period when compared with baseline observed in Study LVGY (NCT00125918) and were merged into 1 reporting group.
    Arm/Group Title Tadalafil 20 mg or 40 mg Double-Blind and 40 mg Open-Label
    Arm/Group Description Tadalafil 20 mg administered orally as 1 tadalafil 20-mg tablet and 1 matched placebo tablet, once daily from Day 1 up to 52 weeks of treatment, or tadalafil 40 mg (two 20-mg tablets) administered orally, once daily from Day 1 up to 52 weeks of treatment in Double-Blind Period; and tadalafil 40 mg (two 20-mg tablets) administered orally, once daily from Week 53 up to Week 243 in Open-Label Period.
    All Cause Mortality
    Tadalafil 20 mg or 40 mg Double-Blind and 40 mg Open-Label
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Tadalafil 20 mg or 40 mg Double-Blind and 40 mg Open-Label
    Affected / at Risk (%) # Events
    Total 184/357 (51.5%)
    Blood and lymphatic system disorders
    Anaemia 7/357 (2%) 11
    Anaemia macrocytic 1/357 (0.3%) 1
    Neutropenia 1/357 (0.3%) 1
    Cardiac disorders
    Acute coronary syndrome 1/357 (0.3%) 1
    Acute myocardial infarction 2/357 (0.6%) 2
    Angina pectoris 3/357 (0.8%) 3
    Angina unstable 1/357 (0.3%) 1
    Aortic valve stenosis 1/357 (0.3%) 1
    Arrhythmia 1/357 (0.3%) 1
    Arrhythmia supraventricular 1/357 (0.3%) 1
    Atrial fibrillation 7/357 (2%) 11
    Atrial flutter 1/357 (0.3%) 1
    Atrial tachycardia 1/357 (0.3%) 1
    Atrioventricular block complete 1/357 (0.3%) 1
    Cardiac arrest 5/357 (1.4%) 5
    Cardiac failure 9/357 (2.5%) 10
    Cardiac failure congestive 10/357 (2.8%) 16
    Cardiac flutter 1/357 (0.3%) 1
    Cardio-respiratory arrest 2/357 (0.6%) 2
    Cardio-respiratory distress 1/357 (0.3%) 1
    Cardiogenic shock 1/357 (0.3%) 1
    Cardiopulmonary failure 1/357 (0.3%) 1
    Cor pulmonale 1/357 (0.3%) 1
    Coronary artery disease 2/357 (0.6%) 2
    Cyanosis 1/357 (0.3%) 1
    Hypertensive heart disease 1/357 (0.3%) 1
    Mitral valve incompetence 1/357 (0.3%) 1
    Myocardial infarction 4/357 (1.1%) 5
    Palpitations 3/357 (0.8%) 3
    Pericardial haemorrhage 1/357 (0.3%) 1
    Right ventricular dysfunction 1/357 (0.3%) 1
    Right ventricular failure 28/357 (7.8%) 36
    Sick sinus syndrome 1/357 (0.3%) 1
    Sinus arrhythmia 1/357 (0.3%) 1
    Supraventricular tachycardia 3/357 (0.8%) 3
    Ventricular tachycardia 1/357 (0.3%) 1
    Ear and labyrinth disorders
    Vertigo 1/357 (0.3%) 1
    Endocrine disorders
    Hypothyroidism 1/357 (0.3%) 1
    Eye disorders
    Cataract 1/357 (0.3%) 1
    Retinal detachment 1/357 (0.3%) 1
    Visual disturbance 1/357 (0.3%) 1
    Gastrointestinal disorders
    Abdominal pain 1/357 (0.3%) 1
    Colitis ischaemic 1/357 (0.3%) 1
    Colonic polyp 1/357 (0.3%) 1
    Dental caries 1/357 (0.3%) 1
    Diarrhoea 2/357 (0.6%) 2
    Duodenal ulcer haemorrhage 1/357 (0.3%) 1
    Gastric volvulus 1/357 (0.3%) 1
    Gastrointestinal haemorrhage 8/357 (2.2%) 10
    Gastrointestinal ulcer 1/357 (0.3%) 1
    Gingival hypertrophy 1/357 (0.3%) 1
    Hiatus hernia 1/357 (0.3%) 2
    Intestinal obstruction 1/357 (0.3%) 1
    Intestinal polyp 1/357 (0.3%) 1
    Lower gastrointestinal haemorrhage 1/357 (0.3%) 1
    Oesophageal achalasia 1/357 (0.3%) 1
    Oesophageal stenosis 1/357 (0.3%) 1
    Pancreatitis 2/357 (0.6%) 2
    Rectal haemorrhage 1/357 (0.3%) 1
    Umbilical hernia 1/357 (0.3%) 1
    General disorders
    Chest discomfort 1/357 (0.3%) 1
    Chest pain 7/357 (2%) 9
    Chills 1/357 (0.3%) 1
    Cyst 1/357 (0.3%) 1
    Death 3/357 (0.8%) 3
    Device malfunction 1/357 (0.3%) 1
    Fatigue 1/357 (0.3%) 1
    Injection site haemorrhage 1/357 (0.3%) 1
    Medical device complication 2/357 (0.6%) 2
    Non-cardiac chest pain 4/357 (1.1%) 4
    Oedema peripheral 5/357 (1.4%) 5
    Pyrexia 3/357 (0.8%) 4
    Sensation of pressure 1/357 (0.3%) 1
    Sudden cardiac death 2/357 (0.6%) 2
    Sudden death 2/357 (0.6%) 2
    Hepatobiliary disorders
    Cholecystitis 1/357 (0.3%) 1
    Cholecystitis acute 1/357 (0.3%) 1
    Cholelithiasis 1/357 (0.3%) 1
    Hepatitis toxic 1/357 (0.3%) 1
    Infections and infestations
    Bacteraemia 2/357 (0.6%) 2
    Bronchiolitis 1/357 (0.3%) 1
    Bronchitis 6/357 (1.7%) 6
    Bronchitis bacterial 1/357 (0.3%) 1
    Campylobacter infection 1/357 (0.3%) 1
    Campylobacter intestinal infection 1/357 (0.3%) 1
    Cellulitis 1/357 (0.3%) 1
    Clostridial infection 2/357 (0.6%) 2
    Clostridium difficile colitis 1/357 (0.3%) 1
    Cystitis 2/357 (0.6%) 2
    Device related infection 1/357 (0.3%) 1
    Diverticulitis 1/357 (0.3%) 1
    Erysipelas 1/357 (0.3%) 1
    Gastroenteritis 1/357 (0.3%) 1
    Gastroenteritis salmonella 1/357 (0.3%) 1
    Gastroenteritis viral 1/357 (0.3%) 1
    Herpes zoster ophthalmic 1/357 (0.3%) 1
    Infection 1/357 (0.3%) 1
    Influenza 2/357 (0.6%) 2
    Lobar pneumonia 1/357 (0.3%) 1
    Lower respiratory tract infection 1/357 (0.3%) 1
    Lung infection 3/357 (0.8%) 3
    Mycobacterial infection 1/357 (0.3%) 1
    Nasopharyngitis 1/357 (0.3%) 2
    Parotitis 1/357 (0.3%) 1
    Pneumonia 16/357 (4.5%) 19
    Pneumonia staphylococcal 1/357 (0.3%) 1
    Pulmonary tuberculosis 1/357 (0.3%) 1
    Respiratory tract infection 1/357 (0.3%) 1
    Sepsis 2/357 (0.6%) 2
    Septic shock 1/357 (0.3%) 1
    Sinusitis 1/357 (0.3%) 1
    Staphylococcal bacteraemia 2/357 (0.6%) 2
    Staphylococcal skin infection 2/357 (0.6%) 2
    Tracheobronchitis 1/357 (0.3%) 1
    Upper respiratory tract infection 1/357 (0.3%) 1
    Urinary tract infection 2/357 (0.6%) 3
    Viral infection 1/357 (0.3%) 1
    Viral upper respiratory tract infection 1/357 (0.3%) 1
    Wound infection 1/357 (0.3%) 1
    Injury, poisoning and procedural complications
    Accidental overdose 1/357 (0.3%) 1
    Cervical vertebral fracture 1/357 (0.3%) 1
    Fall 4/357 (1.1%) 5
    Femur fracture 2/357 (0.6%) 2
    Fibula fracture 1/357 (0.3%) 1
    Fractured sacrum 1/357 (0.3%) 1
    Hip fracture 2/357 (0.6%) 2
    Humerus fracture 1/357 (0.3%) 1
    Incisional hernia 2/357 (0.6%) 2
    Post procedural discharge 1/357 (0.3%) 1
    Post procedural haematoma 1/357 (0.3%) 1
    Postoperative wound complication 1/357 (0.3%) 1
    Pubic rami fracture 1/357 (0.3%) 1
    Rib fracture 1/357 (0.3%) 1
    Road traffic accident 1/357 (0.3%) 1
    Subdural haematoma 1/357 (0.3%) 1
    Therapeutic agent toxicity 1/357 (0.3%) 1
    Tibia fracture 1/357 (0.3%) 1
    Toxicity to various agents 2/357 (0.6%) 3
    Investigations
    Blood pressure increased 1/357 (0.3%) 1
    C-reactive protein increased 1/357 (0.3%) 1
    Cardiac output decreased 1/357 (0.3%) 1
    International normalised ratio increased 1/357 (0.3%) 1
    Metabolism and nutrition disorders
    Dehydration 6/357 (1.7%) 6
    Diabetes mellitus 2/357 (0.6%) 2
    Fluid overload 4/357 (1.1%) 5
    Fluid retention 1/357 (0.3%) 1
    Hyperglycaemia 1/357 (0.3%) 1
    Hypokalaemia 1/357 (0.3%) 1
    Hypomagnesaemia 1/357 (0.3%) 1
    Hyponatraemia 2/357 (0.6%) 2
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/357 (0.3%) 1
    Arthritis 2/357 (0.6%) 2
    Back pain 2/357 (0.6%) 2
    Bunion 1/357 (0.3%) 1
    Bursitis 1/357 (0.3%) 1
    Cervical spinal stenosis 1/357 (0.3%) 1
    Exostosis 1/357 (0.3%) 1
    Intervertebral disc protrusion 2/357 (0.6%) 2
    Musculoskeletal pain 1/357 (0.3%) 1
    Osteoarthritis 1/357 (0.3%) 1
    Osteolysis 1/357 (0.3%) 1
    Osteonecrosis 1/357 (0.3%) 2
    Pain in extremity 2/357 (0.6%) 2
    Rotator cuff syndrome 2/357 (0.6%) 2
    Scleroderma 1/357 (0.3%) 1
    Systemic lupus erythematosus 1/357 (0.3%) 3
    Systemic sclerosis 1/357 (0.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 2/357 (0.6%) 2
    Breast cancer recurrent 2/357 (0.6%) 2
    Colon cancer 1/357 (0.3%) 1
    Leiomyosarcoma metastatic 1/357 (0.3%) 1
    Lung adenocarcinoma 1/357 (0.3%) 1
    Lung neoplasm malignant 2/357 (0.6%) 2
    Multiple myeloma 1/357 (0.3%) 1
    Oesophageal carcinoma 1/357 (0.3%) 1
    Oropharyngeal cancer stage iv 1/357 (0.3%) 1
    Uterine leiomyoma 2/357 (0.6%) 2
    Uterine leiomyosarcoma 1/357 (0.3%) 1
    Nervous system disorders
    Ataxia 1/357 (0.3%) 1
    Cerebrovascular accident 1/357 (0.3%) 1
    Cervical myelopathy 1/357 (0.3%) 1
    Complicated migraine 1/357 (0.3%) 1
    Dementia 1/357 (0.3%) 1
    Depressed level of consciousness 1/357 (0.3%) 1
    Dizziness 1/357 (0.3%) 2
    Dystonia 1/357 (0.3%) 1
    Haemorrhage intracranial 1/357 (0.3%) 1
    Headache 1/357 (0.3%) 2
    Hypoaesthesia 1/357 (0.3%) 1
    Presyncope 2/357 (0.6%) 2
    Syncope 10/357 (2.8%) 10
    Transient ischaemic attack 2/357 (0.6%) 2
    Pregnancy, puerperium and perinatal conditions
    Premature labour 1/357 (0.3%) 1
    Psychiatric disorders
    Anxiety disorder 1/357 (0.3%) 2
    Bipolar disorder 1/357 (0.3%) 1
    Confusional state 1/357 (0.3%) 1
    Delirium 1/357 (0.3%) 1
    Depression 1/357 (0.3%) 1
    Emotional disorder 1/357 (0.3%) 1
    Mental status changes 1/357 (0.3%) 1
    Suicide attempt 2/357 (0.6%) 2
    Withdrawal syndrome 1/357 (0.3%) 1
    Renal and urinary disorders
    Proteinuria 1/357 (0.3%) 1
    Renal failure 2/357 (0.6%) 2
    Renal failure acute 5/357 (1.4%) 7
    Renal failure chronic 1/357 (0.3%) 1
    Renal impairment 1/357 (0.3%) 1
    Reproductive system and breast disorders
    Haemorrhagic ovarian cyst 1/357 (0.3%) 1
    Menorrhagia 1/357 (0.3%) 1
    Ovarian cyst 1/357 (0.3%) 1
    Ovarian cyst ruptured 1/357 (0.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/357 (0.3%) 1
    Aspiration 1/357 (0.3%) 1
    Asthma 2/357 (0.6%) 2
    Bronchial haemorrhage 1/357 (0.3%) 1
    Chronic obstructive pulmonary disease 3/357 (0.8%) 4
    Dyspnoea 5/357 (1.4%) 6
    Dyspnoea exertional 1/357 (0.3%) 1
    Epistaxis 3/357 (0.8%) 5
    Haemoptysis 4/357 (1.1%) 5
    Hypoxia 2/357 (0.6%) 2
    Lung disorder 1/357 (0.3%) 1
    Pleural effusion 4/357 (1.1%) 5
    Pneumothorax 1/357 (0.3%) 2
    Pulmonary arterial hypertension 26/357 (7.3%) 28
    Pulmonary embolism 3/357 (0.8%) 3
    Pulmonary granuloma 1/357 (0.3%) 1
    Pulmonary hypertension 1/357 (0.3%) 1
    Respiratory failure 6/357 (1.7%) 6
    Skin and subcutaneous tissue disorders
    Skin ulcer 3/357 (0.8%) 3
    Surgical and medical procedures
    Skin lesion excision 1/357 (0.3%) 1
    Vascular disorders
    Aortic stenosis 1/357 (0.3%) 1
    Circulatory collapse 1/357 (0.3%) 1
    Haematoma 1/357 (0.3%) 1
    Haemorrhage 2/357 (0.6%) 2
    Hypertension 2/357 (0.6%) 2
    Hypertensive crisis 1/357 (0.3%) 1
    Hypotension 2/357 (0.6%) 2
    Paradoxical embolism 1/357 (0.3%) 1
    Peripheral vascular disorder 1/357 (0.3%) 1
    Thrombosis 1/357 (0.3%) 1
    Other (Not Including Serious) Adverse Events
    Tadalafil 20 mg or 40 mg Double-Blind and 40 mg Open-Label
    Affected / at Risk (%) # Events
    Total 334/357 (93.6%)
    Blood and lymphatic system disorders
    Anaemia 42/357 (11.8%) 51
    Cardiac disorders
    Palpitations 52/357 (14.6%) 61
    Eye disorders
    Vision blurred 22/357 (6.2%) 23
    Gastrointestinal disorders
    Diarrhoea 77/357 (21.6%) 107
    Dyspepsia 35/357 (9.8%) 39
    Gastrooesophageal reflux disease 19/357 (5.3%) 19
    Nausea 44/357 (12.3%) 56
    Vomiting 18/357 (5%) 22
    General disorders
    Asthenia 18/357 (5%) 18
    Chest pain 38/357 (10.6%) 45
    Fatigue 49/357 (13.7%) 56
    Oedema peripheral 63/357 (17.6%) 82
    Infections and infestations
    Bronchitis 34/357 (9.5%) 44
    Influenza 26/357 (7.3%) 31
    Nasopharyngitis 64/357 (17.9%) 110
    Respiratory tract infection 19/357 (5.3%) 30
    Sinusitis 27/357 (7.6%) 42
    Upper respiratory tract infection 63/357 (17.6%) 105
    Urinary tract infection 37/357 (10.4%) 59
    Metabolism and nutrition disorders
    Hypokalaemia 20/357 (5.6%) 25
    Musculoskeletal and connective tissue disorders
    Arthralgia 40/357 (11.2%) 43
    Back pain 64/357 (17.9%) 76
    Muscle spasms 29/357 (8.1%) 31
    Musculoskeletal pain 19/357 (5.3%) 19
    Myalgia 28/357 (7.8%) 30
    Pain in extremity 44/357 (12.3%) 51
    Nervous system disorders
    Dizziness 61/357 (17.1%) 73
    Headache 107/357 (30%) 130
    Syncope 20/357 (5.6%) 25
    Psychiatric disorders
    Anxiety 23/357 (6.4%) 24
    Depression 22/357 (6.2%) 25
    Insomnia 36/357 (10.1%) 37
    Respiratory, thoracic and mediastinal disorders
    Cough 54/357 (15.1%) 61
    Dyspnoea 55/357 (15.4%) 69
    Epistaxis 39/357 (10.9%) 44
    Nasal congestion 27/357 (7.6%) 31
    Pulmonary arterial hypertension 33/357 (9.2%) 41
    Skin and subcutaneous tissue disorders
    Rash 29/357 (8.1%) 32
    Vascular disorders
    Flushing 28/357 (7.8%) 30

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00549302
    Other Study ID Numbers:
    • 10263
    • H6D-MC-LVGX
    First Posted:
    Oct 25, 2007
    Last Update Posted:
    Apr 9, 2013
    Last Verified:
    Apr 1, 2013