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Trial record 1 of 1 for:    NCT01784068
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Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients (ENESTfreedom)

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ClinicalTrials.gov Identifier: NCT01784068
Recruitment Status : Active, not recruiting
First Posted : February 5, 2013
Results First Posted : January 14, 2021
Last Update Posted : November 12, 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: Other
Condition Chronic Myelogenous Leukemia
Intervention Drug: Nilotinib followed by treatment-free
Enrollment 215
Recruitment Details 215 patients were actually enrolled in the NTCS (nilotinib treatment consolidation) phase. 190 of the 215 patients completed 52 weeks of nilotinib treatment in the NTCS phase and entered the treatment-free remission (TFR) phase.
Pre-assignment Details Approximately 175 patients were planned to be enrolled into the study.
Arm/Group Title NTCS Phase TFR Phase
Hide Arm/Group Description Patients who received a minimum of two years of first line nilotinib treatment and with BCR-ABL1 transcript level of MR4.5 entered consolidation phase of the study (52 weeks of nilotinib 300 mg BID) Patients with Minimal Residual Disease (MRD) at the end of consolidation phase entered the Treatment-Free Remission (TFR) phase where no treatment was given
Period Title: NTCS Phase
Started 215 0
NTRI Phase 86 0
NTCT Phase 13 0
TFR-2 Phase 8 0
NTCT-P Phase 2 0
NTRI-2 0 0
Completed [1] 0 0
Not Completed 215 0
Reason Not Completed
Adverse Event             5             0
Physician Decision             2             0
Patient/guardian decision             3             0
Death             2             0
Completed phase = discontinuation of study except for TFR and TFR2 phases             203             0
[1]
Completed = Still on Study Phase which means a patient has no end of study phase completion CRF page as of data Cut-off date: 30-NOV-2015
Period Title: TFR Phase
Started 0 190
Completed 0 97
Not Completed 0 93
Reason Not Completed
Physician Decision             0             1
Patient/guardian decision             0             3
Death             0             1
Lack of Efficacy             0             88
Arm/Group Title NTCS Phase
Hide Arm/Group Description Patients who received a minimum of two years of first line nilotinib treatment and with BCR-ABL1 transcript level of MR4.5 entered consolidation phase of the study (52 weeks of nilotinib 300 mg BID)
Overall Number of Baseline Participants 215
Hide Baseline Analysis Population Description
Safety Set: Safety set included all patients who received at least one dose of study medication.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 215 participants
54.0
(21 to 86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 215 participants
Female
102
  47.4%
Male
113
  52.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 215 participants
Caucasian 189
Asian 20
Unknown 3
Native American 1
Other 2
1.Primary Outcome
Title Percentage of Patients Who Are in MMR (Major Molecular Response) at 48 Weeks After Starting the Treatment-free Remission (TFR) Phase
Hide Description Primary endpoint was the percentage of participants who were in MMR at 48 weeks after starting the TFR phase and is calculated by dividing the number of patients with MMR at 48 weeks after starting the TFR phase with no loss of MMR and no re-initiation of nilotinib therapy in the first 48 weeks after starting the TFR phase by the number of patients who entered the TFR phase. Patients who required re-initiation of treatment were considered as non-responders.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: The FAS included the 190 patients who completed 52 weeks of nilotinib treatment in the NTCS phase and entered TFR phase
Arm/Group Title TFR Phase
Hide Arm/Group Description:
Patients with Minimal Residual Disease (MRD) at the end of consolidation phase entered the Treatment-Free Remission (TFR) phase where no treatment was given
Overall Number of Participants Analyzed 190
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
51.6
(44.2 to 58.9)
2.Secondary Outcome
Title Percentage of Patients Who Are in MR4.5 (BCR-ABL ≤ 0.0032% IS) at 48 Weeks After Starting the TFR Phase
Hide Description Proportion of patients who are in MR4.5 at 48 weeks after starting the TFR phase is calculated by dividing the number of patients with MR4.5 at 48 weeks after starting the TFR phase with no loss of MR4.5 and no re-initiation of nilotinib therapy in the first 48 weeks after starting the TFR phase by the number of patients who entered the TFR phase. Patients who required re-initiation of treatment will be considered as non-responders. MR4.5 = log reductions of the BCR-ABR transcript load in blood as a measurement of deep molecular response of the CML clone to treatment.
Time Frame 48 weeks
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Percentage of Patients Who Are in MMR at 96, 144,192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase
Hide Description Proportion of patients who are in MMR at 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase is calculated by dividing the number of patients with MMR at 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase with no loss of MMR and no re-initiation of nilotinib therapy in the first 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase by the number of patients who entered the TFR phase. Patients who required re-initiation of treatment will be considered as non-responders
Time Frame 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Percentage of Patients Who Are in MR4.5 at 96, 144, 192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase
Hide Description Proportion of patients who are in MR4.5 at 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase is calculated by dividing the number of patients with MR4.5 at 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase with no loss of MR4.5 and no re-initiation of nilotinib therapy in the first 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase by the number of patients who entered the TFR phase. Patients who required re-initiation of treatment will be considered as non-responders
Time Frame 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Percentage of Patients in MMR at 48, 96, 144, 192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase of Nilotinib
Hide Description Proportion of patients who are in MMR at 48, 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase is calculated by dividing the number of patients with MMR at 48, 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase by the number of patients who entered the TFR phase. Patients who are re-initiated with nilotinib but have less than 12 weeks of re-initiation of treatment will be excluded from the analysis
Time Frame 48, 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Percentage of Patients in MR4.5 at 48, 96, 144, 192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase of Nilotinib
Hide Description Proportion of patients who are in MR4.5 at 48, 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase is calculated by dividing the number of patients with MR4.5 at 48, 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase by the number of patients who entered the TFR phase. Patients who are re-initiated with nilotinib but have less than 12 weeks of re-initiation of treatment will be excluded from the analysis
Time Frame 48, 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Percentage of Patients Who Achieve MMR Within 12 Weeks of Re-treatment With Nilotinib
Hide Description Proportion of patients who achieve MMR within 12 weeks of re-initiation of nilotinib is calculated by dividing the number of patients who are in MMR at least at one assessment within 12 weeks after re-start of nilotinib treatment by the number of patients who are re-initiated for at least 12 weeks
Time Frame 12 weeks
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Kinetics of BCR-ABL Transcript After Re-start of Nilotinib Therapy
Hide Description Descriptive statistics of BCR-ABL levels (IS) over time after re-start of nilotinib therapy up to 528 weks after the last patient has entered TFR
Time Frame Every 4 weeks up to week 24 and every 12 weeks thereafter up to 528 weeks after last patient has entered the TFR
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Duration of Re-initiated Treatment Required to Regain MMR After Loss of MMR
Hide Description Defined as time from date of start of re-initiation of treatment after loss of MMR to the date of first achievement of MMR. Patients who do not regain MMR after re-initiation of treatment on or before the cut-off date, duration will be censored at the date of last PCR assessment
Time Frame Every 4 weeks up to week 24 and every 12 weeks thereafter up to 528 weeks after the last patient has entered TFR
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Duration of Re-initiated Treatment Required to Regain MR4.5 After Loss of MMR
Hide Description Defined as the time from start of re-initiation of treatment after loss of MMR to the first achievement of MR4.5. Patients who do not regain MR4.5 after re-initiation of treatment on or before the cut-off date, duration will be censored at the date of last PCR assessment
Time Frame Every 4 weeks up to week 24 and every 12 weeks thereafter up to 528 weeks after the last patient has entered TFR
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Treatment-free Survival (TFS) After the Start of the TFR Phase
Hide Description

TFS is defined as the time from the start of the TFR phase to the earliest occurrence of loss of MMR, re-initiation of treatment due to any cause, progression of AP/BC or death due to any cause. For patients without any event on or before the cut-off date, survival time will be censored at the date of their last assessment (PCR, cytogenetic, hematologic or extramedullary).

A TFS sensitivity analysis will be conducted to consider discontinuation from TFR phase due to any reason as a TFS event, in addition to the TFS events as defined above.

Time Frame Every 4 weeks in the first period of 48 weeks of the TFR, every 6 weeks in the second period of 48 weeks in TFR and every 12 weeks in the last period of 432 weeks of the TFR
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Progression-free Survival (PFS) After the Start of the TFR Phase
Hide Description PFS is defined as the time from the start of the TFR phase to the earliest occurrence of progression to AP/BC or death due to any cause. For patients without any event on or before the cut-off date, survival time will be censored at the date of their last assessment (cytogenetic, hematologic or extramedullary) for patients who are still on study and at the date of last contact for patients who are in follow-up
Time Frame Every 4 weeks in the first period of 48 weeks of the TFR, every 6 weeks in the second period of 48 weeks of TFR and every 12 weeks in the last period of 432 weeks of the TFR
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Overall Survival (OS) After the Start of the TFR Phase
Hide Description OS is defined as the time from start of the TFR phase to death due to any cause. For patients without any event on or before the cut-off date, survival time will be censored at the date of their last assessment for patients who are still on study and at the date of last contact for patients who are in follow-up
Time Frame Every 4 weeks in the first period of 48 weeks of the TFR, every 6 weeks in the second period of 48 weeks of TFR and every 12 weeks in the last period of 432 weeks of the TFR
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Safety Profile During the Nilotinib Treatment Consolidation Phase, During the TFR Phase and During Re-initiation Treatment With Nilotinib
Hide Description Safety profile includes type, frequency and severity of adverse events, laboratory abnormalities and clinically notable ECG and other safety parameters during the nilotinib treatment consolidation phase, during the TFR phase and during re-initiation of treatment with nilotinib
Time Frame Every 4 weeks in treatment consolidation and during the first 24 weeks of the re-initiation phase, every 12 weeks thereafter. Every 4, 6 and 12 weeks respectively in the first and second period of 48 weeks and in the last period of 432 weeks of the TFR
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Proportion of Patients Who Develop T3151, E255K/V, Y253H, F359V/C/I Mutations on Study or Any Other BCR-ABL Mutations in Patients Who Lost MMR After Nilotinib Suspension
Hide Description Proportion will be calculated by dividing the number of patients who developT315I, E255K/V, Y253H, F359V/C/I mutations after nilotinib suspension by the number of patients who lost MMR
Time Frame Every 3 months in patients who lost MMR until the result is negative or up to 528 weeks after the last patient entered TFR. On average 3 analyses (every 3 months or up to 264 weeks after the last patient has entered TFR.)
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Percentage of Patients Who Are in Stable Response (MMR and MR4.5) After Achievement of That Response in Nilotinib Re-initiation Phase for 48, 96, 144, 192, 240, 288, 336, 384 and 432 Weeks, Based on Availability of Appropriate Data
Hide Description Proportion of patients who are in stable MMR/MR4.5 after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384 and 432 weeks, based on availability of appropriate data, is calculated by dividing the number of patients achieving MMR/MR4.5 any time during the nilotinib re-initiation phase and having the same response 48, 96, 144, 192, 240, 288, 336, 384 and 432 weeks after the first achievement of MMR/MR4.5, irrespective of whether there is loss of MMR in between, by the number of patients who achieved MMR/MR4.5 at any time during the nilotinib re-initiation phase
Time Frame 48, 96, 144, 192, 240, 288, 336, 384 and 432 weeks
Outcome Measure Data Not Reported
Time Frame Adverse events were collected from first dose of study treatment until 30 days after the last dose of study treatment or the last day in the TFR/TFR-2 phase for approx. 26 months.
Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment plus 30 days post treatment.
 
Arm/Group Title NTCS Phase TFR Phase NTRI Phase NTCT Phase TFR-2 Phase NTRI-2 Phase NTCT-P Phase All Patients
Hide Arm/Group Description Patients who received a minimum of two years of first line nilotinib treatment and with BCR-ABL1 transcript level of MR4.5 entered consolidation phase of the study (52 weeks of nilotinib 300 mg BID) Patients with Minimal Residual Disease (MRD) at the end of consolidation phase entered the Treatment-Free Remission (TFR) phase where no treatment was given If at any time during TFR phase the patient lost MMR, nilotinib treatment was to be immediately re-initiated (nilotinib 300 mg BID) Patients with no MRD at the end of consolidation phase entered the continuation phase of the study and continue with nilotinib 300 mg BID Patients with MRD at the end of the continuation phase entered the TFR-2 phase of the study where no treatment was given If at any time during TFR phase or TFR-2 phase the patient lost MMR, nilotinib treatment was to be immediately re-initiated (nilotinib 300 mg BID) Patients with no MRD at the end of continuation phase entered the prolonged continuation phase of the study All patients enrolled in the study
All-Cause Mortality
NTCS Phase TFR Phase NTRI Phase NTCT Phase TFR-2 Phase NTRI-2 Phase NTCT-P Phase All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/215 (0.93%)   1/190 (0.53%)   2/86 (2.33%)   0/13 (0.00%)   0/8 (0.00%)   0/0   0/2 (0.00%)   5/215 (2.33%) 
Hide Serious Adverse Events
NTCS Phase TFR Phase NTRI Phase NTCT Phase TFR-2 Phase NTRI-2 Phase NTCT-P Phase All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   20/215 (9.30%)   15/190 (7.89%)   11/86 (12.79%)   1/13 (7.69%)   0/8 (0.00%)   0/0   0/2 (0.00%)   40/215 (18.60%) 
Cardiac disorders                 
ACUTE MYOCARDIAL INFARCTION  1  0/215 (0.00%)  1/190 (0.53%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
ANGINA PECTORIS  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
CARDIAC ARREST  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
CARDIAC FAILURE CONGESTIVE  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
CORONARY ARTERY DISEASE  1  0/215 (0.00%)  0/190 (0.00%)  2/86 (2.33%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
MYOCARDIAL INFARCTION  1  1/215 (0.47%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
Eye disorders                 
IRIS NEOVASCULARISATION  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Gastrointestinal disorders                 
ABDOMINAL PAIN  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
ABDOMINAL PAIN UPPER  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
ASCITES  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
GASTRIC ULCER  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
HAEMORRHOIDS  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
INGUINAL HERNIA  1  2/215 (0.93%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  3/215 (1.40%) 
NAUSEA  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
PANCREATITIS  1  2/215 (0.93%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
General disorders                 
CHEST PAIN  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
DEATH  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
GENERALISED OEDEMA  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Hepatobiliary disorders                 
CHOLELITHIASIS  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
HEPATOMEGALY  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Immune system disorders                 
CONTRAST MEDIA ALLERGY  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
DRUG HYPERSENSITIVITY  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Infections and infestations                 
DACRYOCYSTITIS  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
HERPES ZOSTER  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
PHARYNGEAL ABSCESS  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
RESPIRATORY TRACT INFECTION  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Injury, poisoning and procedural complications                 
ANKLE FRACTURE  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Metabolism and nutrition disorders                 
TYPE 2 DIABETES MELLITUS  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Musculoskeletal and connective tissue disorders                 
BACK PAIN  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
CHONDROPATHY  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
INTERVERTEBRAL DISC PROTRUSION  1  2/215 (0.93%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  3/215 (1.40%) 
ROTATOR CUFF SYNDROME  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
BASAL CELL CARCINOMA  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
BREAST CANCER  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
BREAST CANCER IN SITU  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
MALIGNANT MELANOMA  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
MESOTHELIOMA  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
RECTAL CANCER  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
THYROID NEOPLASM  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
TRANSITIONAL CELL CARCINOMA  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Nervous system disorders                 
CEREBRAL INFARCTION  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
CEREBROVASCULAR ACCIDENT  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
DIZZINESS  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
HEADACHE  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
MULTIPLE SCLEROSIS RELAPSE  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
SCIATICA  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
SYNCOPE  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
TRANSIENT ISCHAEMIC ATTACK  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Psychiatric disorders                 
COMPLETED SUICIDE  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Renal and urinary disorders                 
HAEMORRHAGE URINARY TRACT  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
RENAL COLIC  1  0/215 (0.00%)  0/190 (0.00%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
URINARY INCONTINENCE  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Respiratory, thoracic and mediastinal disorders                 
DYSPNOEA  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
PLEURAL EFFUSION  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
PNEUMONIA ASPIRATION  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Vascular disorders                 
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE  1  2/215 (0.93%)  2/190 (1.05%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  4/215 (1.86%) 
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NTCS Phase TFR Phase NTRI Phase NTCT Phase TFR-2 Phase NTRI-2 Phase NTCT-P Phase All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   136/215 (63.26%)   91/190 (47.89%)   49/86 (56.98%)   10/13 (76.92%)   1/8 (12.50%)   0/0   0/2 (0.00%)   171/215 (79.53%) 
Gastrointestinal disorders                 
ABDOMINAL PAIN UPPER  1  9/215 (4.19%)  6/190 (3.16%)  3/86 (3.49%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  15/215 (6.98%) 
DIARRHOEA  1  12/215 (5.58%)  9/190 (4.74%)  2/86 (2.33%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  22/215 (10.23%) 
NAUSEA  1  7/215 (3.26%)  2/190 (1.05%)  3/86 (3.49%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  10/215 (4.65%) 
VOMITING  1  6/215 (2.79%)  5/190 (2.63%)  1/86 (1.16%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  11/215 (5.12%) 
General disorders                 
FATIGUE  1  9/215 (4.19%)  6/190 (3.16%)  4/86 (4.65%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  18/215 (8.37%) 
INFLUENZA LIKE ILLNESS  1  3/215 (1.40%)  2/190 (1.05%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  6/215 (2.79%) 
LOCALISED OEDEMA  1  0/215 (0.00%)  1/190 (0.53%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
Infections and infestations                 
GASTROENTERITIS  1  3/215 (1.40%)  1/190 (0.53%)  3/86 (3.49%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  8/215 (3.72%) 
INFLUENZA  1  7/215 (3.26%)  4/190 (2.11%)  2/86 (2.33%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  11/215 (5.12%) 
LARYNGITIS  1  1/215 (0.47%)  1/190 (0.53%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  4/215 (1.86%) 
NASOPHARYNGITIS  1  22/215 (10.23%)  17/190 (8.95%)  7/86 (8.14%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  36/215 (16.74%) 
PHARYNGITIS  1  2/215 (0.93%)  1/190 (0.53%)  3/86 (3.49%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  6/215 (2.79%) 
UPPER RESPIRATORY TRACT INFECTION  1  7/215 (3.26%)  9/190 (4.74%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  16/215 (7.44%) 
Injury, poisoning and procedural complications                 
FALL  1  5/215 (2.33%)  0/190 (0.00%)  3/86 (3.49%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  7/215 (3.26%) 
LIGAMENT SPRAIN  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
LIP INJURY  1  0/215 (0.00%)  0/190 (0.00%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
Investigations                 
BLOOD CHOLESTEROL INCREASED  1  6/215 (2.79%)  4/190 (2.11%)  5/86 (5.81%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  14/215 (6.51%) 
BLOOD CREATININE INCREASED  1  1/215 (0.47%)  1/190 (0.53%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  3/215 (1.40%) 
LIPASE INCREASED  1  8/215 (3.72%)  2/190 (1.05%)  7/86 (8.14%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  15/215 (6.98%) 
Metabolism and nutrition disorders                 
DECREASED APPETITE  1  2/215 (0.93%)  2/190 (1.05%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  6/215 (2.79%) 
HYPERCHOLESTEROLAEMIA  1  2/215 (0.93%)  3/190 (1.58%)  7/86 (8.14%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  10/215 (4.65%) 
HYPERTRIGLYCERIDAEMIA  1  1/215 (0.47%)  0/190 (0.00%)  1/86 (1.16%)  3/13 (23.08%)  0/8 (0.00%)  0/0  0/2 (0.00%)  4/215 (1.86%) 
HYPOPHOSPHATAEMIA  1  16/215 (7.44%)  2/190 (1.05%)  5/86 (5.81%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  17/215 (7.91%) 
Musculoskeletal and connective tissue disorders                 
ARTHRALGIA  1  17/215 (7.91%)  23/190 (12.11%)  4/86 (4.65%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  39/215 (18.14%) 
ARTHRITIS  1  1/215 (0.47%)  1/190 (0.53%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  3/215 (1.40%) 
BACK PAIN  1  9/215 (4.19%)  7/190 (3.68%)  3/86 (3.49%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  19/215 (8.84%) 
BONE PAIN  1  4/215 (1.86%)  9/190 (4.74%)  2/86 (2.33%)  0/13 (0.00%)  0/8 (0.00%)  0/0  0/2 (0.00%)  13/215 (6.05%) 
MUSCLE SPASMS  1  7/215 (3.26%)  4/190 (2.11%)  4/86 (4.65%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  14/215 (6.51%) 
MUSCULOSKELETAL PAIN  1  6/215 (2.79%)  7/190 (3.68%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  14/215 (6.51%) 
MYALGIA  1  3/215 (1.40%)  9/190 (4.74%)  3/86 (3.49%)  1/13 (7.69%)  1/8 (12.50%)  0/0  0/2 (0.00%)  15/215 (6.98%) 
PAIN IN EXTREMITY  1  8/215 (3.72%)  13/190 (6.84%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  22/215 (10.23%) 
ROTATOR CUFF SYNDROME  1  0/215 (0.00%)  2/190 (1.05%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  3/215 (1.40%) 
Nervous system disorders                 
AMNESIA  1  0/215 (0.00%)  0/190 (0.00%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
HEADACHE  1  9/215 (4.19%)  11/190 (5.79%)  6/86 (6.98%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  24/215 (11.16%) 
Psychiatric disorders                 
ANXIETY  1  1/215 (0.47%)  3/190 (1.58%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  4/215 (1.86%) 
DEPRESSION  1  3/215 (1.40%)  1/190 (0.53%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  5/215 (2.33%) 
Reproductive system and breast disorders                 
MENSTRUATION IRREGULAR  1  1/215 (0.47%)  0/190 (0.00%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  2/215 (0.93%) 
Respiratory, thoracic and mediastinal disorders                 
COUGH  1  7/215 (3.26%)  1/190 (0.53%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  10/215 (4.65%) 
DYSPHONIA  1  0/215 (0.00%)  0/190 (0.00%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  1/215 (0.47%) 
DYSPNOEA  1  6/215 (2.79%)  1/190 (0.53%)  1/86 (1.16%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  8/215 (3.72%) 
OROPHARYNGEAL PAIN  1  4/215 (1.86%)  1/190 (0.53%)  3/86 (3.49%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  9/215 (4.19%) 
Skin and subcutaneous tissue disorders                 
DRY SKIN  1  5/215 (2.33%)  1/190 (0.53%)  0/86 (0.00%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  7/215 (3.26%) 
PRURITUS  1  4/215 (1.86%)  2/190 (1.05%)  8/86 (9.30%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  15/215 (6.98%) 
RASH  1  7/215 (3.26%)  1/190 (0.53%)  3/86 (3.49%)  2/13 (15.38%)  0/8 (0.00%)  0/0  0/2 (0.00%)  13/215 (6.05%) 
Vascular disorders                 
HYPERTENSION  1  16/215 (7.44%)  7/190 (3.68%)  3/86 (3.49%)  1/13 (7.69%)  0/8 (0.00%)  0/0  0/2 (0.00%)  24/215 (11.16%) 
1
Term from vocabulary, MedDRA (18.1)
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.
Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI 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 pooled data (i.e.,data from all sites) in 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: NCT01784068    
Other Study ID Numbers: CAMN107I2201
2012-004092-40 ( EudraCT Number )
First Submitted: January 30, 2013
First Posted: February 5, 2013
Results First Submitted: December 18, 2020
Results First Posted: January 14, 2021
Last Update Posted: November 12, 2021