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Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia

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ClinicalTrials.gov Identifier: NCT00782067
Recruitment Status : Completed
First Posted : October 29, 2008
Results First Posted : June 6, 2017
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia
Intervention Drug: Midostaurin (PKC412)
Enrollment 116
Recruitment Details This study was conducted at 29 centers in 12 countries worldwide (Australia, Austria, Belgium, Canada, France, Germany, Netherlands, Norway, Poland, Turkey, United Kingdom, United States).
Pre-assignment Details The Participant Flow was on the Full Analysis Set (FAS), the Baseline Characteristics were done on the FAS and Primary Efficacy Population (PEP). The Efficacy analysis was done on the PEP (except for the Overall Survival which was done on FAS and PEP). The Safety analysis was done on the Safety Set (SS).
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Period Title: Overall Study
Started [1] 116
Safety Set (SS) [2] 116
Primary Efficacy Population (PEP) [3] 89
Completed 0
Not Completed 116
Reason Not Completed
Adverse Event             35
Subject withdrew consent             11
Lost to Follow-up             2
Administrative problems             14
Death             9
Disease progression             43
Protocol deviation             2
[1]
All patients to whom study treatment had been assigned (FAS)
[2]
All patients who received at least one dose of study drug
[3]
FAS patients meeting diagnostic criteria for ASM/MCL presenting at least one measurable C-finding
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Baseline Participants 116
Hide Baseline Analysis Population Description
The Participant Flow was on the Full Analysis Set (FAS), the Baseline Characteristics were done on the FAS and Primary Efficacy Population (PEP). The Efficacy analysis was done on the PEP (except for the Overall Survival which was done on FAS and PEP). The Safety analysis was done on the Safety Set (SS).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 116 participants
61.8  (11.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants
Female
40
  34.5%
Male
76
  65.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   1.7%
White
111
  95.7%
More than one race
0
   0.0%
Unknown or Not Reported
3
   2.6%
Age Continuous (PEP)   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 89 participants
63.0  (11.59)
[1]
Measure Analysis Population Description: Primary Efficacy Population (PEP)
Sex: Female, Male (PEP)   [1] 
Measure Type: Number
Unit of measure:  Participants
PEP (n=89) - Female Number Analyzed 89 participants
32
PEP (n=89) - Male Number Analyzed 89 participants
57
[1]
Measure Analysis Population Description: Primary Efficacy Population (PEP)
Race (PEP)   [1] 
Measure Type: Number
Unit of measure:  Participants
PEP (n=89) - Black Number Analyzed 89 participants
1
PEP (n=89) - White Number Analyzed 89 participants
86
PEP (n=89) - Other/Missing Number Analyzed 89 participants
2
[1]
Measure Analysis Population Description: Primary Efficacy Population (PEP)
1.Primary Outcome
Title Percentage of Participants With Overall Response Rate (ORR)
Hide Description

Overall Response Rate (ORR) was defined as the percentage of participants who classified as confirmed responders (Major Response (MR) or Partial Response (PR)) by the adjudication of the SSC and based on a Modified Valent Criteria.

A major responder had complete resolution of at least one C-Finding and no progression in other C-Findings. A partial responder showed a measurable improvement in one or more C-Finding(s) without confirmed progression in other C-Findings. A C-Finding was a Clinical Finding, which was considered by the investigator and corroborated by the Study Steering Committee (SSC) Chairperson or designee, attributable to the mast cell disease component and not the associated hematological clonal non-mast cell lineage disease (AHNMD) component or any other cause.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population: participants assigned to study treatment who met diagnostic criteria for aggressive systemic mastocytosis or mast cell leukemia and presented with at least 1 measurable C-Finding at study entry and/or participants with transfusion dependent anemia due to their underlying disease at study entry as confirmed by the SCC.
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description:
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Participants Analyzed 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
59.6
(48.6 to 69.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Midostaurin (PKC412)
Comments [Not Specified]
Type of Statistical Test Other
Comments Single arm study
Statistical Test of Hypothesis P-Value <0.001
Comments Null hypothesis: ORR <= 30% Alternative hypothesis: ORR >= 50%
Method Exact Binomial Test
Comments [Not Specified]
Other Statistical Analysis Exact Binomial 95% Confidence Interval
2.Secondary Outcome
Title Median Time to Duration of Response (DoR)
Hide Description The Duration of response (DoR) was defined as the time from first onset of confirmed response (MR or PR) to the date of first documented and confirmed progression or death due to ASM/MCL.
Time Frame Up 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population (PEP), which consisted of all participants with a confirmed response, was considered.
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description:
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Participants Analyzed 89
Median (95% Confidence Interval)
Unit of Measure: Months
31.4 [1] 
(10.8 to NA)
[1]
Not Estimable because no event occured after median survival time
3.Secondary Outcome
Title Median Time to Response (TTR)
Hide Description The Time to response (TTR) was defined as the time from start of treatment until the date of onset of confirmed response (MR or PR).
Time Frame Up 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population (PEP), which consisted of all participants with a confirmed response, was considered.
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description:
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Participants Analyzed 89
Median (Full Range)
Unit of Measure: Months
0.3
(0.1 to 3.7)
4.Secondary Outcome
Title Median Time to Progression-Free Survival (PFS)
Hide Description The Progression-free survival (PFS) is defined as the time from start of treatment to the date of the first documented and confirmed progression or death due to any cause.
Time Frame Up 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population (PEP), which consisted of all participants with a confirmed response, was considered.
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description:
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Participants Analyzed 89
Median (95% Confidence Interval)
Unit of Measure: Months
17.0
(10.2 to 24.8)
5.Secondary Outcome
Title Median Time to Overall Survival (OS)
Hide Description The Overall Survival (OS) is defined as the time from start of treatment to the date of death due to any cause.
Time Frame Up 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population (PEP), which consisted of all participants with a confirmed response and the Full Analysis Set (FAS), which consisted of all patients who received at least one dose of study drug were considered.
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description:
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Participants Analyzed 116
Median (95% Confidence Interval)
Unit of Measure: Months
Primary Efficacy Population (PEP) (n=89) Number Analyzed 89 participants
26.8
(17.6 to 34.4)
Full Analysis Set (FAS) (n=116) Number Analyzed 116 participants
28.7
(20.3 to 38.0)
6.Secondary Outcome
Title Long-term Safety and Tolerability of Midostaurin
Hide Description Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC)
Time Frame Up to 30 days after last dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set (SS)
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description:
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Participants Analyzed 116
Measure Type: Number
Unit of Measure: Percentage of participants
AEs by Primary System Organ Class (SOC) (n=116) Number Analyzed 116 participants
100
SAEs by Primary System Organ Class (SOC) (n=88) Number Analyzed 88 participants
75.9
Deaths by Primary System Organ Class (SOC) (n=25) Number Analyzed 25 participants
21.6
7.Secondary Outcome
Title Histopathologic Response
Hide Description Histopathologic response was summarized to demonstrate the change from baseline in percentage of mast cell infiltrations in the Bone Marrow (BM) and related serum tryptase levels.
Time Frame Up 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population (PEP); for each patient, the best improvement relative to Baseline was considered.
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description:
Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
Overall Number of Participants Analyzed 89
Measure Type: Number
Unit of Measure: Percentage of participants
>50% decrease in mast cell (MC) (n=41) Number Analyzed 41 participants
46.1
>0-<=50% decrease in mast cell (MC) (n=19) Number Analyzed 19 participants
21.3
>50% decrease in serum tryptase (n=52) Number Analyzed 52 participants
58.4
>0-<=50% decrease in serum tryptase (n=25) Number Analyzed 25 participants
28.1
Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 8 years and 7 months.
Adverse Event Reporting Description Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
 
Arm/Group Title Midostaurin (PKC412)
Hide Arm/Group Description Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.
All-Cause Mortality
Midostaurin (PKC412)
Affected / at Risk (%)
Total   25/116 (21.55%) 
Show Serious Adverse Events Hide Serious Adverse Events
Midostaurin (PKC412)
Affected / at Risk (%)
Total   88/116 (75.86%) 
Blood and lymphatic system disorders   
Anaemia  1  8/116 (6.90%) 
Coagulopathy  1  1/116 (0.86%) 
Cytopenia  1  1/116 (0.86%) 
Disseminated intravascular coagulation  1  1/116 (0.86%) 
Eosinophilia  1  1/116 (0.86%) 
Febrile neutropenia  1  6/116 (5.17%) 
Granulocytopenia  1  1/116 (0.86%) 
Leukocytosis  1  3/116 (2.59%) 
Lymphadenopathy  1  1/116 (0.86%) 
Mastocytosis  1  1/116 (0.86%) 
Neutropenia  1  1/116 (0.86%) 
Splenic infarction  1  2/116 (1.72%) 
Thrombocytopenia  1  1/116 (0.86%) 
Cardiac disorders   
Acute myocardial infarction  1  1/116 (0.86%) 
Angina pectoris  1  1/116 (0.86%) 
Aortic valve stenosis  1  2/116 (1.72%) 
Atrial fibrillation  1  2/116 (1.72%) 
Bradycardia  1  1/116 (0.86%) 
Cardiac arrest  1  2/116 (1.72%) 
Cardiac failure  1  2/116 (1.72%) 
Cardiac failure chronic  1  1/116 (0.86%) 
Cardiac failure congestive  1  1/116 (0.86%) 
Coronary artery disease  1  3/116 (2.59%) 
Extrasystoles  1  1/116 (0.86%) 
Heart valve incompetence  1  1/116 (0.86%) 
Left ventricular failure  1  1/116 (0.86%) 
Myocardial infarction  1  2/116 (1.72%) 
Right ventricular failure  1  1/116 (0.86%) 
Sinus tachycardia  1  1/116 (0.86%) 
Tachycardia  1  1/116 (0.86%) 
Ventricular tachycardia  1  2/116 (1.72%) 
Congenital, familial and genetic disorders   
Aplasia  1  1/116 (0.86%) 
Ear and labyrinth disorders   
Ear disorder  1  1/116 (0.86%) 
Eye disorders   
Papilloedema  1  1/116 (0.86%) 
Retinopathy hypertensive  1  1/116 (0.86%) 
Uveitis  1  1/116 (0.86%) 
Gastrointestinal disorders   
Abdominal discomfort  1  1/116 (0.86%) 
Abdominal hernia  1  1/116 (0.86%) 
Abdominal pain  1  1/116 (0.86%) 
Abdominal pain upper  1  1/116 (0.86%) 
Ascites  1  5/116 (4.31%) 
Colitis  1  2/116 (1.72%) 
Constipation  1  1/116 (0.86%) 
Diarrhoea  1  8/116 (6.90%) 
Gastric haemorrhage  1  1/116 (0.86%) 
Gastric ulcer  1  2/116 (1.72%) 
Gastric varices haemorrhage  1  1/116 (0.86%) 
Gastritis  1  1/116 (0.86%) 
Gastritis haemorrhagic  1  1/116 (0.86%) 
Gastrointestinal disorder  1  2/116 (1.72%) 
Gastrointestinal haemorrhage  1  7/116 (6.03%) 
Gastrointestinal toxicity  1  1/116 (0.86%) 
Gastrointestinal ulcer haemorrhage  1  1/116 (0.86%) 
Haemorrhoids  1  1/116 (0.86%) 
Intestinal haemorrhage  1  1/116 (0.86%) 
Intestinal mass  1  1/116 (0.86%) 
Lower gastrointestinal haemorrhage  1  1/116 (0.86%) 
Melaena  1  1/116 (0.86%) 
Nausea  1  1/116 (0.86%) 
Oesophageal varices haemorrhage  1  2/116 (1.72%) 
Pancreatitis acute  1  1/116 (0.86%) 
Small intestinal obstruction  1  1/116 (0.86%) 
Stomatitis  1  1/116 (0.86%) 
Umbilical hernia  1  1/116 (0.86%) 
Umbilical hernia, obstructive  1  1/116 (0.86%) 
Upper gastrointestinal haemorrhage  1  3/116 (2.59%) 
Varices oesophageal  1  1/116 (0.86%) 
Vomiting  1  5/116 (4.31%) 
General disorders   
Asthenia  1  1/116 (0.86%) 
Disease progression  1  2/116 (1.72%) 
Fatigue  1  3/116 (2.59%) 
General physical health deterioration  1  2/116 (1.72%) 
Generalised oedema  1  1/116 (0.86%) 
Malaise  1  2/116 (1.72%) 
Multiple organ dysfunction syndrome  1  3/116 (2.59%) 
Oedema peripheral  1  2/116 (1.72%) 
Pyrexia  1  7/116 (6.03%) 
Hepatobiliary disorders   
Bile duct stenosis  1  1/116 (0.86%) 
Cholecystitis  1  1/116 (0.86%) 
Cholecystitis chronic  1  1/116 (0.86%) 
Cholelithiasis  1  1/116 (0.86%) 
Hepatic cirrhosis  1  1/116 (0.86%) 
Hepatic failure  1  2/116 (1.72%) 
Hepatorenal syndrome  1  1/116 (0.86%) 
Immune system disorders   
Anaphylactic shock  1  1/116 (0.86%) 
Infections and infestations   
Bronchitis  1  1/116 (0.86%) 
Campylobacter colitis  1  1/116 (0.86%) 
Cellulitis  1  1/116 (0.86%) 
Clostridium difficile colitis  1  1/116 (0.86%) 
Endocarditis  1  1/116 (0.86%) 
Erysipelas  1  2/116 (1.72%) 
Escherichia urinary tract infection  1  1/116 (0.86%) 
Gastroenteritis  1  1/116 (0.86%) 
Herpes zoster  1  1/116 (0.86%) 
Infection  1  1/116 (0.86%) 
Intervertebral discitis  1  1/116 (0.86%) 
Lung infection  1  1/116 (0.86%) 
Malaria  1  1/116 (0.86%) 
Nocardiosis  1  1/116 (0.86%) 
Otitis externa  1  1/116 (0.86%) 
Otitis media  1  1/116 (0.86%) 
Peritonitis  1  1/116 (0.86%) 
Pneumonia  1  11/116 (9.48%) 
Sepsis  1  10/116 (8.62%) 
Sinusitis  1  1/116 (0.86%) 
Skin bacterial infection  1  1/116 (0.86%) 
Splenic infection  1  1/116 (0.86%) 
Staphylococcal sepsis  1  1/116 (0.86%) 
Upper respiratory tract infection  1  1/116 (0.86%) 
Urethritis  1  1/116 (0.86%) 
Urinary tract infection  1  5/116 (4.31%) 
Wound infection  1  1/116 (0.86%) 
Injury, poisoning and procedural complications   
Lumbar vertebral fracture  1  1/116 (0.86%) 
Muscle strain  1  1/116 (0.86%) 
Post procedural haematoma  1  1/116 (0.86%) 
Postoperative ileus  1  1/116 (0.86%) 
Stoma site haemorrhage  1  1/116 (0.86%) 
Subdural haematoma  1  1/116 (0.86%) 
Transfusion reaction  1  1/116 (0.86%) 
Transfusion related complication  1  1/116 (0.86%) 
Wound dehiscence  1  1/116 (0.86%) 
Investigations   
Amylase increased  1  1/116 (0.86%) 
Bleeding time prolonged  1  1/116 (0.86%) 
Electrocardiogram QT prolonged  1  1/116 (0.86%) 
Electrocardiogram ST segment depression  1  1/116 (0.86%) 
Troponin increased  1  1/116 (0.86%) 
Metabolism and nutrition disorders   
Failure to thrive  1  1/116 (0.86%) 
Gout  1  1/116 (0.86%) 
Hypercalcaemia  1  1/116 (0.86%) 
Hyperglycaemia  1  2/116 (1.72%) 
Tumour lysis syndrome  1  1/116 (0.86%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/116 (0.86%) 
Bone pain  1  1/116 (0.86%) 
Intervertebral disc protrusion  1  1/116 (0.86%) 
Muscle haemorrhage  1  1/116 (0.86%) 
Musculoskeletal stiffness  1  1/116 (0.86%) 
Myalgia  1  1/116 (0.86%) 
Osteolysis  1  1/116 (0.86%) 
Osteonecrosis of jaw  1  1/116 (0.86%) 
Osteosclerosis  1  1/116 (0.86%) 
Spinal pain  1  1/116 (0.86%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute leukaemia  1  2/116 (1.72%) 
Acute myeloid leukaemia  1  5/116 (4.31%) 
Adenocarcinoma of colon  1  1/116 (0.86%) 
Haematological malignancy  1  1/116 (0.86%) 
Lung neoplasm malignant  1  1/116 (0.86%) 
Myelofibrosis  1  1/116 (0.86%) 
Refractory cytopenia with unilineage dysplasia  1  1/116 (0.86%) 
Squamous cell carcinoma  1  1/116 (0.86%) 
Tumour compression  1  1/116 (0.86%) 
Nervous system disorders   
Cerebrovascular accident  1  1/116 (0.86%) 
Headache  1  1/116 (0.86%) 
Intracranial aneurysm  1  1/116 (0.86%) 
Loss of consciousness  1  1/116 (0.86%) 
Memory impairment  1  1/116 (0.86%) 
Restless legs syndrome  1  1/116 (0.86%) 
Seizure  1  3/116 (2.59%) 
Psychiatric disorders   
Anxiety  1  1/116 (0.86%) 
Insomnia  1  1/116 (0.86%) 
Mental status changes  1  1/116 (0.86%) 
Renal and urinary disorders   
Acute kidney injury  1  4/116 (3.45%) 
Calculus urinary  1  1/116 (0.86%) 
Renal failure  1  5/116 (4.31%) 
Renal impairment  1  1/116 (0.86%) 
Urethral stenosis  1  1/116 (0.86%) 
Urinary retention  1  1/116 (0.86%) 
Reproductive system and breast disorders   
Ovarian cyst  1  1/116 (0.86%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  6/116 (5.17%) 
Epistaxis  1  3/116 (2.59%) 
Orthopnoea  1  1/116 (0.86%) 
Pleural effusion  1  5/116 (4.31%) 
Pneumonitis  1  1/116 (0.86%) 
Pulmonary haemorrhage  1  1/116 (0.86%) 
Respiratory failure  1  2/116 (1.72%) 
Tachypnoea  1  1/116 (0.86%) 
Skin and subcutaneous tissue disorders   
Angioedema  1  1/116 (0.86%) 
Rash papular  1  1/116 (0.86%) 
Skin ulcer  1  2/116 (1.72%) 
Toxic skin eruption  1  3/116 (2.59%) 
Surgical and medical procedures   
Heart valve operation  1  1/116 (0.86%) 
Vascular disorders   
Arterial occlusive disease  1  1/116 (0.86%) 
Flushing  1  1/116 (0.86%) 
Haemodynamic instability  1  1/116 (0.86%) 
Hypotension  1  2/116 (1.72%) 
Peripheral artery stenosis  1  1/116 (0.86%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Midostaurin (PKC412)
Affected / at Risk (%)
Total   115/116 (99.14%) 
Blood and lymphatic system disorders   
Anaemia  1  39/116 (33.62%) 
Leukopenia  1  7/116 (6.03%) 
Neutropenia  1  17/116 (14.66%) 
Thrombocytopenia  1  23/116 (19.83%) 
Ear and labyrinth disorders   
Vertigo  1  6/116 (5.17%) 
Gastrointestinal disorders   
Abdominal distension  1  7/116 (6.03%) 
Abdominal pain  1  34/116 (29.31%) 
Abdominal pain upper  1  10/116 (8.62%) 
Ascites  1  9/116 (7.76%) 
Constipation  1  29/116 (25.00%) 
Diarrhoea  1  62/116 (53.45%) 
Dyspepsia  1  7/116 (6.03%) 
Flatulence  1  6/116 (5.17%) 
Nausea  1  94/116 (81.03%) 
Vomiting  1  77/116 (66.38%) 
General disorders   
Chills  1  6/116 (5.17%) 
Fatigue  1  33/116 (28.45%) 
Oedema  1  6/116 (5.17%) 
Oedema peripheral  1  41/116 (35.34%) 
Pain  1  7/116 (6.03%) 
Pyrexia  1  30/116 (25.86%) 
Infections and infestations   
Bronchitis  1  8/116 (6.90%) 
Cystitis  1  7/116 (6.03%) 
Oral herpes  1  6/116 (5.17%) 
Pneumonia  1  6/116 (5.17%) 
Sinusitis  1  6/116 (5.17%) 
Upper respiratory tract infection  1  12/116 (10.34%) 
Urinary tract infection  1  14/116 (12.07%) 
Viral upper respiratory tract infection  1  20/116 (17.24%) 
Injury, poisoning and procedural complications   
Contusion  1  7/116 (6.03%) 
Investigations   
Alanine aminotransferase increased  1  6/116 (5.17%) 
Amylase increased  1  7/116 (6.03%) 
Blood alkaline phosphatase increased  1  9/116 (7.76%) 
Blood creatinine increased  1  6/116 (5.17%) 
Electrocardiogram QT prolonged  1  12/116 (10.34%) 
Gamma-glutamyltransferase increased  1  11/116 (9.48%) 
Lipase increased  1  11/116 (9.48%) 
Weight decreased  1  10/116 (8.62%) 
Metabolism and nutrition disorders   
Decreased appetite  1  11/116 (9.48%) 
Hyperglycaemia  1  8/116 (6.90%) 
Hyperkalaemia  1  7/116 (6.03%) 
Hypocalcaemia  1  6/116 (5.17%) 
Hypokalaemia  1  11/116 (9.48%) 
Hypomagnesaemia  1  7/116 (6.03%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  24/116 (20.69%) 
Back pain  1  26/116 (22.41%) 
Muscle spasms  1  13/116 (11.21%) 
Musculoskeletal pain  1  19/116 (16.38%) 
Myalgia  1  8/116 (6.90%) 
Pain in extremity  1  9/116 (7.76%) 
Nervous system disorders   
Disturbance in attention  1  8/116 (6.90%) 
Dizziness  1  16/116 (13.79%) 
Headache  1  29/116 (25.00%) 
Paraesthesia  1  6/116 (5.17%) 
Psychiatric disorders   
Anxiety  1  8/116 (6.90%) 
Depression  1  13/116 (11.21%) 
Insomnia  1  11/116 (9.48%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  22/116 (18.97%) 
Dyspnoea  1  17/116 (14.66%) 
Epistaxis  1  14/116 (12.07%) 
Oropharyngeal pain  1  6/116 (5.17%) 
Pleural effusion  1  9/116 (7.76%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  7/116 (6.03%) 
Hyperhidrosis  1  6/116 (5.17%) 
Night sweats  1  10/116 (8.62%) 
Pruritus  1  24/116 (20.69%) 
Rash  1  7/116 (6.03%) 
Vascular disorders   
Flushing  1  8/116 (6.90%) 
Haematoma  1  6/116 (5.17%) 
Hypotension  1  11/116 (9.48%) 
1
Term from vocabulary, MedDRA (20.0)
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
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00782067     History of Changes
Other Study ID Numbers: CPKC412D2201
2008-000280-42 ( EudraCT Number )
First Submitted: October 28, 2008
First Posted: October 29, 2008
Results First Submitted: May 3, 2017
Results First Posted: June 6, 2017
Last Update Posted: November 15, 2018