Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2010-021344-17 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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The purpose of this study was to investigate the effects of QTI571 (imatinib) on pharmacokinetics of bosentan and sildenafil at steady state when co-administered to participants with pulmonary arterial hypertension.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Imatinib + Bosentan + Sildenafil | Experimental | Participants received treatment with bosentan 125 milligrams (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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imatinib | Drug | Film coated tablets, oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Ratio of Dose Normalized Area Under the Curve From Time Zero to Tau (AUCtau) for Bosentan Before and After Imatinib Administrations | 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). | 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 |
| Geometric Mean Ratio of Dose Normalized AUCtau for Sildenafil Before and After Imatinib Administrations | 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). | 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 |
| Geometric Mean Ratio of Dose Normalized Maximum Plasma Concentration (Cmax) for Bosentan Before and After Imatinib Administrations |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With At Least One or More Adverse Events (AEs) | 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. | From time of first administration of study drug until end of study (up to approximately 18 months) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Tampa | Florida | 33606 | United States | ||
| Novartis Investigative Site |
Not provided
Participants with pulmonary arterial hypertension (PAH) were enrolled in the study at 8 investigation sites worldwide from 20 April 2011 to 25 October 2012.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Imatinib+ Bosentan+ Sildenafil | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Sildenafil | Drug | Oral Administration |
|
| Bosentan | Drug | Oral Administration |
|
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). |
| 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 |
| Geometric Mean Ratio of Dose Normalized Cmax for Sildenafil Before and After Imatinib Administrations | 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). | 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 |
| Dose Normalized Cmax of Imatinib and CGP74588 (Active Metabolite of Imatinib) | 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 |
| Dose Normalized AUCtau of Imatinib and CGP74588 (Active Metabolite of Imatinib) | 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 |
| Weston |
| Florida |
| 33331 |
| United States |
| Novartis Investigative Site | Mineola | New York | 11501 | United States |
| Novartis Investigative Site | Darlinghurst | New South Wales | 2010 | Australia |
| Novartis Investigative Site | Brussels | 1070 | Belgium |
| Novartis Investigative Site | Leuven | 3000 | Belgium |
| Novartis Investigative Site | Berlin | 12683 | Germany |
| Novartis Investigative Site | Hanover | 30625 | Germany |
| Novartis Investigative Site | Roma | RM | 00161 | Italy |
| Novartis Investigative Site | Vilnius | LT-08661 | Lithuania |
| Novartis Investigative Site | London | NW3 2PR | United Kingdom |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety analysis set included all participants enrolled and who received at least one dose of study drug (bosentan, sildenafil, or imatinib).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Imatinib+ Bosentan+ Sildenafil | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Geometric Mean Ratio of Dose Normalized Area Under the Curve From Time Zero to Tau (AUCtau) for Bosentan Before and After Imatinib Administrations | 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL/mg | 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 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Geometric Mean Ratio of Dose Normalized AUCtau for Sildenafil Before and After Imatinib Administrations | 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL/mg | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Geometric Mean Ratio of Dose Normalized Maximum Plasma Concentration (Cmax) for Bosentan Before and After Imatinib Administrations | 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL/mg | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Geometric Mean Ratio of Dose Normalized Cmax for Sildenafil Before and After Imatinib Administrations | 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL/mg | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With At Least One or More Adverse Events (AEs) | 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. | Safety analysis set included all participants enrolled and who received at least one dose of study drug (bosentan, sildenafil, or imatinib). | Posted | Count of Participants | Participants | From time of first administration of study drug until end of study (up to approximately 18 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Dose Normalized Cmax of Imatinib and CGP74588 (Active Metabolite of Imatinib) | 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. | Posted | Mean | Standard Deviation | ng/ml/mg | 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 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Dose Normalized AUCtau of Imatinib and CGP74588 (Active Metabolite of Imatinib) | 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. | Posted | Mean | Standard Deviation | hr*ng/mL/mg | 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 |
|
|
From time of first administration of study drug until end of study (up to approximately 18 months)
Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bosentan + Sildenafil | Participants received treatment with bosentan 125 mg twice daily and sildenafil thrice daily for 8 days in treatment period 1 | 0 | 21 | 0 | 21 | 10 | 21 |
| EG001 | Imatinib (200 mg/Day) + Bosentan + Sildenafil | 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. | 0 | 19 | 2 | 19 | 9 | 19 |
| EG002 | Imatinib (400 mg/Day) + Bosentan+ Sildenafil | 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. | 0 | 18 | 1 | 18 | 16 | 18 |
| EG003 | Total Participants | 0 | 21 | 2 | 21 | 19 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial flutter | Cardiac disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Atrioventricular block first degree | Cardiac disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Extrasystoles | Cardiac disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Eyelid oedema | Eye disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Head discomfort | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Telangiectasia | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (unspecified) | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068877 | Imatinib Mesylate |
| D000068677 | Sildenafil Citrate |
| D000077300 | Bosentan |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D000096926 | Benzenesulfonamides |
Not provided
Not provided
| Ratio (Test/Reference) |
| 1.40 |
| 2-Sided |
| 90 |
| 1.23 |
| 1.59 |
| Superiority |
| OG001 | Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1) | 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. |
| OG002 | Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 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. |
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| OG001 | Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1) | 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. |
| OG002 | Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 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. |
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| OG001 | Imatinib (200 mg/Day) + Bosentan + Sildenafil (Test 1) | 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. |
| OG002 | Imatinib (400 mg/Day) + Bosentan + Sildenafil (Test 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. |
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