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Pharmacokinetic Effects of QTI571 on Sildenafil and Bosentan in Pulmonary Arterial Hypertension Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01392469
Recruitment Status : Completed
First Posted : July 12, 2011
Results First Posted : June 21, 2021
Last Update Posted : June 21, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Interventions Drug: Imatinib
Drug: Sildenafil
Drug: Bosentan
Enrollment 21
Recruitment Details Participants with pulmonary arterial hypertension (PAH) were enrolled in the study at 8 investigation sites worldwide from 20 April 2011 to 25 October 2012.
Pre-assignment Details  
Arm/Group Title Imatinib+ Bosentan+ Sildenafil
Hide Arm/Group Description Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1. Participants were on the same sildenafil dose level (20, 40, 50 or 60 mg) they had been at study entry which was well tolerated in conjunction with bosentan. Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2. Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Period Title: Overall Study
Started 21
Completed 17
Not Completed 4
Reason Not Completed
Adverse Event             2
Withdrawal by Subject             1
Protocol Violation             1
Arm/Group Title Imatinib+ Bosentan+ Sildenafil
Hide Arm/Group Description Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1. Participants were on the same sildenafil dose level (20, 40, 50 or 60 mg) they had been at study entry which was well tolerated in conjunction with bosentan. Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2. Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Baseline Participants 21
Hide Baseline Analysis Population Description
Safety analysis set included all participants enrolled and who received at least one dose of study drug (bosentan, sildenafil, or imatinib).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants
54.4  (13.44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Female
15
  71.4%
Male
6
  28.6%
1.Primary Outcome
Title Geometric Mean Ratio of Dose Normalized Area Under the Curve From Time Zero to Tau (AUCtau) for Bosentan Before and After Imatinib Administrations
Hide Description AUCtau was the area under the curve calculated to the end of the dosing interval, tau. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of bosentan was performed on dose normalized AUCtau of bosentan. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals were then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).
Time Frame Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics (PK) analysis set included all participants with data for at least one of the primary PK variables in at least one period and no major protocol deviations with impact on PK data.
Arm/Group Title Bosentan + Sildenafil (Reference) Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1) Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Hide Arm/Group Description:
Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1. Participants were on the same sildenafil dose level (20, 40, 50 or 60 mg) they had been at study entry which was well tolerated in conjunction with bosentan
Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2.
Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Participants Analyzed 17 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL/mg
93.3
(49.9%)
109
(52.0%)
131
(38.0%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.17
Confidence Interval (2-Sided) 90%
1.03 to 1.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.40
Confidence Interval (2-Sided) 90%
1.23 to 1.59
Estimation Comments [Not Specified]
2.Primary Outcome
Title Geometric Mean Ratio of Dose Normalized AUCtau for Sildenafil Before and After Imatinib Administrations
Hide Description AUCtau was the area under the curve calculated to the end of the dosing interval, tau. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of sildenafil was performed on dose normalized AUCtau of sildenafil. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals were then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).
Time Frame Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants with data for at least one of the primary PK variables in at least one period and no major protocol deviations with impact on PK data.
Arm/Group Title Bosentan + Sildenafil (Reference) Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1) Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Hide Arm/Group Description:
Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1. Participants were on the same sildenafil dose level (20, 40, 50 or 60 mg) they had been at study entry which was well tolerated in conjunction with bosentan.
Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2.
Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Participants Analyzed 17 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL/mg
7.22
(60.6%)
9.82
(42.5%)
12.3
(40.9%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.36
Confidence Interval (2-Sided) 90%
1.14 to 1.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.70
Confidence Interval (2-Sided) 90%
1.43 to 2.03
Estimation Comments [Not Specified]
3.Primary Outcome
Title Geometric Mean Ratio of Dose Normalized Maximum Plasma Concentration (Cmax) for Bosentan Before and After Imatinib Administrations
Hide Description Cmax was the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after dose administration. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of bosentan was performed on dose normalized Cmax of bosentan. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals were then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).
Time Frame Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants with data for at least one of the primary PK variables in at least one period and no major protocol deviations with impact on PK data.
Arm/Group Title Bosentan + Sildenafil (Reference) Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1) Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Hide Arm/Group Description:
Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1. Participants were on the same sildenafil dose level (20, 40, 50 or 60 mg) they had been at study entry which was well tolerated in conjunction with bosentan.
Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2.
Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Participants Analyzed 17 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL/mg
21.9
(48.8%)
21.8
(60.3%)
23.4
(44.7%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.00
Confidence Interval (2-Sided) 90%
0.82 to 1.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.07
Confidence Interval (2-Sided) 90%
0.88 to 1.31
Estimation Comments [Not Specified]
4.Primary Outcome
Title Geometric Mean Ratio of Dose Normalized Cmax for Sildenafil Before and After Imatinib Administrations
Hide Description Cmax was the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after dose administration. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of sildenafil was performed on dose normalized Cmax of sildenafil. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals was then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).
Time Frame Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants with data for at least one of the primary PK variables in at least one period and no major protocol deviations with impact on PK data.
Arm/Group Title Bosentan + Sildenafil (Reference) Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1) Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Hide Arm/Group Description:
Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1. Participants were on the same sildenafil dose level (20, 40, 50 or 60 mg) they had been at study entry which was well tolerated in conjunction with bosentan.
Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2.
Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Participants Analyzed 17 17 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL/mg
2.44
(68.6%)
3.14
(52.4%)
3.81
(52.9%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.28
Confidence Interval (2-Sided) 90%
1.03 to 1.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bosentan + Sildenafil (Reference), Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Test/Reference)
Estimated Value 1.56
Confidence Interval (2-Sided) 90%
1.24 to 1.95
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With At Least One or More Adverse Events (AEs)
Hide Description An adverse event was the appearance or worsening of any undesirable sign, symptom, or medical condition that occurred after starting the study drug even if the event was not considered to be related to study drug. Number of participants with AEs were reported by treatment period.
Time Frame From time of first administration of study drug until end of study (up to approximately 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants enrolled and who received at least one dose of study drug (bosentan, sildenafil, or imatinib).
Arm/Group Title Bosentan + Sildenafil Imatinib (200 mg/Day) + Bosentan + Sildenafil Imatinib (400 mg/Day) + Bosentan+ Sildenafil
Hide Arm/Group Description:
Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1
Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2.
Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Participants Analyzed 21 19 18
Measure Type: Count of Participants
Unit of Measure: Participants
10
  47.6%
9
  47.4%
16
  88.9%
6.Secondary Outcome
Title Dose Normalized Cmax of Imatinib and CGP74588 (Active Metabolite of Imatinib)
Hide Description [Not Specified]
Time Frame Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants with data for at least one of the primary PK variables in at least one period and no major protocol deviations with impact on PK data.
Arm/Group Title Imatinib (200 mg/Day) + Bosentan + Sildenafil Imatinib (400 mg/Day) + Bosentan + Sildenafil
Hide Arm/Group Description:
Participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2.
Participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Participants Analyzed 17 17
Mean (Standard Deviation)
Unit of Measure: ng/ml/mg
Imatinib Cmax/Dose 7.55  (4.18) 6.71  (3.39)
CGP74588 Cmax/Dose 1.37  (0.538) 1.39  (0.575)
7.Secondary Outcome
Title Dose Normalized AUCtau of Imatinib and CGP74588 (Active Metabolite of Imatinib)
Hide Description [Not Specified]
Time Frame Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants with data for at least one of the primary PK variables in at least one period and no major protocol deviations with impact on PK data.
Arm/Group Title Imatinib (200 mg/Day) + Bosentan + Sildenafil Imatinib (400 mg/Day) + Bosentan + Sildenafil
Hide Arm/Group Description:
Participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2.
Participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.
Overall Number of Participants Analyzed 17 17
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL/mg
Imatinib AUCtau/Dose 90.9  (49.3) 88.4  (36.0)
CGP74588 AUCtau/Dose 19.3  (9.69) 20.6  (9.07)
Time Frame From time of first administration of study drug until end of study (up to approximately 18 months)
Adverse Event Reporting Description Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement
 
Arm/Group Title Bosentan + Sildenafil Imatinib (200 mg/Day) + Bosentan + Sildenafil Imatinib (400 mg/Day) + Bosentan+ Sildenafil Total Participants
Hide Arm/Group Description Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1 Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2. Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg tablet daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3. [Not Specified]
All-Cause Mortality
Bosentan + Sildenafil Imatinib (200 mg/Day) + Bosentan + Sildenafil Imatinib (400 mg/Day) + Bosentan+ Sildenafil Total Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)   0/19 (0.00%)   0/18 (0.00%)   0/21 (0.00%) 
Hide Serious Adverse Events
Bosentan + Sildenafil Imatinib (200 mg/Day) + Bosentan + Sildenafil Imatinib (400 mg/Day) + Bosentan+ Sildenafil Total Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)   2/19 (10.53%)   1/18 (5.56%)   2/21 (9.52%) 
Cardiac disorders         
Atrial flutter  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Cardiac failure congestive  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Infections and infestations         
Viral infection  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Skin and subcutaneous tissue disorders         
Rash  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
1
Term from vocabulary, MedDRA (unspecified)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Bosentan + Sildenafil Imatinib (200 mg/Day) + Bosentan + Sildenafil Imatinib (400 mg/Day) + Bosentan+ Sildenafil Total Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/21 (47.62%)   9/19 (47.37%)   16/18 (88.89%)   19/21 (90.48%) 
Blood and lymphatic system disorders         
Anaemia  1  1/21 (4.76%)  1/19 (5.26%)  3/18 (16.67%)  4/21 (19.05%) 
Neutropenia  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Thrombocytopenia  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Cardiac disorders         
Atrioventricular block first degree  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Extrasystoles  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Palpitations  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Tachycardia  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Ear and labyrinth disorders         
Vertigo  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Endocrine disorders         
Hypothyroidism  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Eye disorders         
Eyelid oedema  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Periorbital oedema  1  0/21 (0.00%)  1/19 (5.26%)  1/18 (5.56%)  2/21 (9.52%) 
Vision blurred  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Gastrointestinal disorders         
Abdominal discomfort  1  0/21 (0.00%)  1/19 (5.26%)  1/18 (5.56%)  2/21 (9.52%) 
Abdominal pain  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Ascites  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Diarrhoea  1  1/21 (4.76%)  5/19 (26.32%)  2/18 (11.11%)  7/21 (33.33%) 
Dry mouth  1  0/21 (0.00%)  1/19 (5.26%)  1/18 (5.56%)  2/21 (9.52%) 
Gingival bleeding  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Haemorrhoidal haemorrhage  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Nausea  1  1/21 (4.76%)  4/19 (21.05%)  2/18 (11.11%)  7/21 (33.33%) 
Toothache  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Vomiting  1  0/21 (0.00%)  1/19 (5.26%)  4/18 (22.22%)  5/21 (23.81%) 
General disorders         
Chest discomfort  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Fatigue  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Oedema peripheral  1  2/21 (9.52%)  1/19 (5.26%)  3/18 (16.67%)  5/21 (23.81%) 
Infections and infestations         
Nasopharyngitis  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Rhinitis  1  0/21 (0.00%)  1/19 (5.26%)  1/18 (5.56%)  2/21 (9.52%) 
Upper respiratory tract infection  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Urinary tract infection  1  0/21 (0.00%)  0/19 (0.00%)  2/18 (11.11%)  2/21 (9.52%) 
Injury, poisoning and procedural complications         
Accidental overdose  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Investigations         
Blood bilirubin increased  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Blood creatinine increased  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Blood glucose increased  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Blood potassium decreased  1  0/21 (0.00%)  1/19 (5.26%)  3/18 (16.67%)  4/21 (19.05%) 
Metabolism and nutrition disorders         
Decreased appetite  1  0/21 (0.00%)  1/19 (5.26%)  1/18 (5.56%)  2/21 (9.52%) 
Hypokalaemia  1  1/21 (4.76%)  0/19 (0.00%)  1/18 (5.56%)  2/21 (9.52%) 
Iron deficiency  1  1/21 (4.76%)  0/19 (0.00%)  1/18 (5.56%)  2/21 (9.52%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  0/21 (0.00%)  2/19 (10.53%)  0/18 (0.00%)  2/21 (9.52%) 
Muscle spasms  1  0/21 (0.00%)  0/19 (0.00%)  2/18 (11.11%)  2/21 (9.52%) 
Musculoskeletal pain  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Myalgia  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Pain in extremity  1  1/21 (4.76%)  2/19 (10.53%)  1/18 (5.56%)  2/21 (9.52%) 
Nervous system disorders         
Dizziness  1  3/21 (14.29%)  0/19 (0.00%)  0/18 (0.00%)  3/21 (14.29%) 
Head discomfort  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Headache  1  1/21 (4.76%)  2/19 (10.53%)  1/18 (5.56%)  4/21 (19.05%) 
Hypoaesthesia  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Paraesthesia  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Presyncope  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Psychiatric disorders         
Insomnia  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Sleep disorder  1  1/21 (4.76%)  0/19 (0.00%)  0/18 (0.00%)  1/21 (4.76%) 
Renal and urinary disorders         
Renal failure  1  1/21 (4.76%)  0/19 (0.00%)  1/18 (5.56%)  2/21 (9.52%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/21 (0.00%)  1/19 (5.26%)  1/18 (5.56%)  2/21 (9.52%) 
Dyspnoea  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Epistaxis  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Pleural effusion  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Skin and subcutaneous tissue disorders         
Dry skin  1  0/21 (0.00%)  1/19 (5.26%)  0/18 (0.00%)  1/21 (4.76%) 
Rash  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Telangiectasia  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
Vascular disorders         
Hypotension  1  0/21 (0.00%)  0/19 (0.00%)  1/18 (5.56%)  1/21 (4.76%) 
1
Term from vocabulary, MedDRA (unspecified)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01392469    
Other Study ID Numbers: CQTI571A2102
2010-021344-17 ( EudraCT Number )
First Submitted: May 10, 2011
First Posted: July 12, 2011
Results First Submitted: April 30, 2021
Results First Posted: June 21, 2021
Last Update Posted: June 21, 2021