A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01077544
Collaborator
(none)
15
Enrollment
12
Locations
2
Arms
50.6
Actual Duration (Months)
1.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the pharmacokinetics of nilotinib in Ph+ CML pediatric patients that are newly diagnosed or resistant or intolerant to imatinib or dasatinib or refractory or relapsed Ph+ ALL compared to the adult populations. It will also evaluate safety and activity of nilotinib as secondary objectives.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-center, Open-label, Pharmacokinetic Study of Oral Nilotinib in Pediatric Patients With Newly Diagnosed Chronic Phase (CP) Ph+ CML, With CP or Accelerated Phase (AP) Ph+ CML Resistant/Intolerant to Imatinib and/or Dasatinib, or With Refractory/Relapsed Ph+ ALL
Actual Study Start Date :
Apr 14, 2011
Actual Primary Completion Date :
Jul 1, 2015
Actual Study Completion Date :
Jul 1, 2015

Arms and Interventions

ArmIntervention/Treatment
Experimental: Group 1

1 year to < 10 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.

Drug: Nilotinib
Nilotinib capsules were delivered in bottles with dose strengths of 50mg, 150mg and 200mg. Patients were administered nilotinib 230 mg/m2 (per BSA) bid, orally, rounded to the nearest 50 mg (max single dose 400 mg) for 28 days (1 cycle) for up to 12 cycles prior to protocol amendment 3 and up to 24 cycles post amendment 3. Capsules were to be swallowed whole with water. Apple sauce (puréed apple) may have been used as a vehicle for dosing where capsules were not able to be swallowed whole with water.
Other Names:
  • AMN107
  • Experimental: Group 2

    >= 10 years to <18 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.

    Drug: Nilotinib
    Nilotinib capsules were delivered in bottles with dose strengths of 50mg, 150mg and 200mg. Patients were administered nilotinib 230 mg/m2 (per BSA) bid, orally, rounded to the nearest 50 mg (max single dose 400 mg) for 28 days (1 cycle) for up to 12 cycles prior to protocol amendment 3 and up to 24 cycles post amendment 3. Capsules were to be swallowed whole with water. Apple sauce (puréed apple) may have been used as a vehicle for dosing where capsules were not able to be swallowed whole with water.
    Other Names:
  • AMN107
  • Outcome Measures

    Primary Outcome Measures

    1. Summary of Nilotinib Non-compartmental PK Parameters: Cmax [Cycle 1 Day 1]

      The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

    2. Summary of Nilotinib Non-compartmental PK Parameters: Tmax [Cycle 1 Day 1]

      The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

    3. Summary of Nilotinib Non-compartmental PK Parameters: AUClast (Last = 24h) [Cycle 1 Day 1]

      The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

    4. Summary of Nilotinib Non-compartmental PK Parameters: AUC0-12h [Cycle 1 Day 1]

      The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

    5. Summary of Nilotinib Steady-state PK Parameters: AUCss [Cycle 1 Day 8 - Cycle 1 Day 28]

      The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses

    6. Summary of Nilotinib Steady-state PK Parameters: CLF (Body Surface Area (BSA) Adjusted) [Cycle 1 Day 8 - Cycle 1 day 28]

      The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses

    7. Summary of Nilotinib Steady-state PK Parameters: Cmin [Cycle 1 Day 8 - Cycle 1 Day 28]

      The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose.

    Secondary Outcome Measures

    1. Number of Ph+ CML Participants With Confirmed Complete Hematologic Response (CHR) [minimum of 12 cycles (28 days per cycle)]

      A confirmed complete hematological response (CHR) is defined when all of the following criteria are achieved at two consecutive assessments, at least 4 weeks apart: white blood cell (WBC) count < 10 × 109/L; platelet < 450 × 109/L; basophils < 5%; no blasts and promyelocytes in peripheral blood (PB); myelocytes + metamyelocytes < 5% in PB; and no extramedullary involvement. The information used for hematological assessment was to be obtained from the laboratory and extramedullary data, all merged by patient and date.

    2. Number of Ph+ CML Participants With Cytogenic Response [minimum of 12 cycles (28 days per cycle)]

      Cytogenetic response was initially assessed as the percentage of Ph+ metaphases in the bone marrow (BM) and performed within 21 days prior to study entry. A major cytogenetic response (0% to 35% Ph+ metaphases test positive for the Philadelphia chromosome) combines both complete cytogenetic (CCyR) and partial cytogenetic response (PCyR). CCyR implies 0% Ph+ metaphases in the BM, PCyR is > 0% to 35%, minor cytogenetic response (mCyR) is > 35% to 65%, minimal response is > 65% to 95% and no response is > 95% Ph+ metaphases in the BM.

    3. Number of Ph+ CML Participants With Major Molecular Response (MMR) [minimum of 12 cycles (28 days per cycle)]

      The bcr-abl gene fusion encodes for a BCR-ABL fusion protein. Depending on the precise location of the fusion, the molecular weight of this protein can range from 185 to 210 kDa. Consequently BCR-ABL is referred to as p185 or p210 transcript. For the patients expressing the major BCR-ABL transcript p210, molecular response was defined and reported as the percent ratio of BCR-ABL transcripts/control gene transcripts converted to a reference standard according to the International Scale (IS). A major molecular response (MMR) is defined as a BCR-ABL/control gene ratio ≤ 0.1% (equal to a 3 log reduction in BCR-ABL transcripts) on the IS. In this study, the control gene was abl.

    4. Efficacy Endpoints for Ph+ ALL Patients [minimum of 12 cycles (28 days per cycle)]

      Best Response in Ph+ ALL patients was defined as either Complete Remission (CR) with platelet recovery, Complete Remission (CR) with incomplete platelet recovery, Partial Remission (PR) or Stable disease. Stable disease was defined is defined as failure to qualify for either CR, PR, or progressive disease.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Must have one of the following: newly diagnosed CP Ph+CML, CP or AP resistant/ intolerant to imatinib and/or dasatinib, or Ph+ ALL either relapsed after or refractory to standard therapy

    • adequate renal, hepatic and pancreatic function

    Exclusion Criteria:
    • patients receiving therapy with strong CYP3A4 inhibitors and/or inducers and treatments cannot be stopped or changed to a different medication at least 14 days prior to starting study drug

    • patients receiving therapy with any medications with a known risk or possible risk to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.

    • gastrointestinal impairment or disease that may interfere with drug absorption

    • liver, pancreatic or severe renal disease unrelated to disease under study

    • impaired cardiac function

    • patients who received dasatinib within 3 days of starting study drug

    • patients who received imatinib within 5 days of starting study drug

    • patients receiving hydroxyurea or corticosteroids that has not been discontinued at least 1 week after initiation of nilotinib

    • patients who received hematopoietic growth factors within 7 days of starting study drug or Pegfilgrastim (Neulasta®) within 14 days of starting study drug

    • patients with Stem Cell Transplant (SCT) or Rescue without TBI: Evidence of active graft vs. host disease and < 3 months since SCT

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Novartis Investigative SiteBordeauxAquitaineFrance33076
    2Novartis Investigative SiteLille cedexFrance59037
    3Novartis Investigative SiteParisFrance75571
    4Novartis Investigative SitePoitiersFrance86021
    5Novartis Investigative SiteMonzaMBItaly20900
    6Novartis Investigative SitePadovaPDItaly35128
    7Novartis Investigative SiteRomaRMItaly00161
    8Novartis Investigative SiteAmsterdamNetherlands1081 HV
    9Novartis Investigative SiteRotterdamNetherlands3015 CN
    10Novartis Investigative SiteWest MidlandsBirminghamUnited KingdomB4 6NH
    11Novartis Investigative SiteSuttonSurreyUnited KingdomSM2 5PT
    12Novartis Investigative SiteBristolUnited KingdomBS2 8BJ

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01077544
    Other Study ID Numbers:
    • CAMN107A2120
    • 2010-018419-14
    First Posted:
    Mar 1, 2010
    Last Update Posted:
    Dec 29, 2020
    Last Verified:
    Oct 1, 2020

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Period Title: Overall Study
    STARTED87
    COMPLETED52
    NOT COMPLETED35

    Baseline Characteristics

    Arm/Group TitleGroup 1Group 2Total
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patientsTotal of all reporting groups
    Overall Participants8715
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    6.8
    (1.16)
    13.7
    (2.81)
    10.0
    (4.12)
    Sex: Female, Male (Count of Participants)
    Female
    3
    37.5%
    4
    57.1%
    7
    46.7%
    Male
    5
    62.5%
    3
    42.9%
    8
    53.3%
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    24.60
    (4.739)
    48.89
    (17.533)
    35.93
    (17.328)
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    119.9
    (7.49)
    158.0
    (16.32)
    137.7
    (23.02)
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    16.962
    (1.7654)
    18.944
    (3.4563)
    17.887
    (2.7795)

    Outcome Measures

    1. Primary Outcome
    TitleSummary of Nilotinib Non-compartmental PK Parameters: Cmax
    DescriptionThe full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
    Time FrameCycle 1 Day 1

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants77
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    405.111
    (42.5)
    402.715
    (35.2)
    2. Secondary Outcome
    TitleNumber of Ph+ CML Participants With Confirmed Complete Hematologic Response (CHR)
    DescriptionA confirmed complete hematological response (CHR) is defined when all of the following criteria are achieved at two consecutive assessments, at least 4 weeks apart: white blood cell (WBC) count < 10 × 109/L; platelet < 450 × 109/L; basophils < 5%; no blasts and promyelocytes in peripheral blood (PB); myelocytes + metamyelocytes < 5% in PB; and no extramedullary involvement. The information used for hematological assessment was to be obtained from the laboratory and extramedullary data, all merged by patient and date.
    Time Frameminimum of 12 cycles (28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS): consists of all patients who passed the screening and are enrolled into the study. Patients may or may not have taken study drug.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants56
    Yes
    5
    62.5%
    5
    71.4%
    No
    0
    0%
    1
    14.3%
    3. Primary Outcome
    TitleSummary of Nilotinib Non-compartmental PK Parameters: Tmax
    DescriptionThe full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
    Time FrameCycle 1 Day 1

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants77
    Median (Full Range) [h]
    2.000
    (163.1050)
    3.000
    (140.8314)
    4. Primary Outcome
    TitleSummary of Nilotinib Non-compartmental PK Parameters: AUClast (Last = 24h)
    DescriptionThe full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
    Time FrameCycle 1 Day 1

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants77
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    4160.969
    (38.5)
    5707.368
    (51.2)
    5. Primary Outcome
    TitleSummary of Nilotinib Non-compartmental PK Parameters: AUC0-12h
    DescriptionThe full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
    Time FrameCycle 1 Day 1

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants77
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    2795.782
    (35.7)
    3393.296
    (30.4)
    6. Primary Outcome
    TitleSummary of Nilotinib Steady-state PK Parameters: AUCss
    DescriptionThe steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses
    Time FrameCycle 1 Day 8 - Cycle 1 Day 28

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants77
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    15129.182
    (38.0)
    14383.076
    (33.6)
    7. Primary Outcome
    TitleSummary of Nilotinib Steady-state PK Parameters: CLF (Body Surface Area (BSA) Adjusted)
    DescriptionThe steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses
    Time FrameCycle 1 Day 8 - Cycle 1 day 28

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants77
    Geometric Mean (Geometric Coefficient of Variation) [L/h/m^2)]
    15.356
    (38.7)
    15.922
    (37.0)
    8. Primary Outcome
    TitleSummary of Nilotinib Steady-state PK Parameters: Cmin
    DescriptionThe full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose.
    Time FrameCycle 1 Day 8 - Cycle 1 Day 28

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants77
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    804.791
    (33.7)
    1072.850
    (20.5)
    9. Secondary Outcome
    TitleNumber of Ph+ CML Participants With Cytogenic Response
    DescriptionCytogenetic response was initially assessed as the percentage of Ph+ metaphases in the bone marrow (BM) and performed within 21 days prior to study entry. A major cytogenetic response (0% to 35% Ph+ metaphases test positive for the Philadelphia chromosome) combines both complete cytogenetic (CCyR) and partial cytogenetic response (PCyR). CCyR implies 0% Ph+ metaphases in the BM, PCyR is > 0% to 35%, minor cytogenetic response (mCyR) is > 35% to 65%, minimal response is > 65% to 95% and no response is > 95% Ph+ metaphases in the BM.
    Time Frameminimum of 12 cycles (28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    FAS consist of all patients (pts) who passed screening & are enrolled into study. Patients may or may not have taken study drug. One (1) Ph+ CML patient in Group 2 was Ph+ at baseline & discontinued study prior to subsequent cytogenetic assessment. This pt doesn't appear in any cytogenic response category.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants56
    Complete cytogenic response (CCyR)
    2
    25%
    2
    28.6%
    Partial cytogenic response (PCyR)
    0
    0%
    1
    14.3%
    Minor cytogenic response (mCyR)
    0
    0%
    1
    14.3%
    Minimal
    0
    0%
    0
    0%
    None
    0
    0%
    0
    0%
    Absence of Ph+ at baseline
    3
    37.5%
    1
    14.3%
    10. Secondary Outcome
    TitleNumber of Ph+ CML Participants With Major Molecular Response (MMR)
    DescriptionThe bcr-abl gene fusion encodes for a BCR-ABL fusion protein. Depending on the precise location of the fusion, the molecular weight of this protein can range from 185 to 210 kDa. Consequently BCR-ABL is referred to as p185 or p210 transcript. For the patients expressing the major BCR-ABL transcript p210, molecular response was defined and reported as the percent ratio of BCR-ABL transcripts/control gene transcripts converted to a reference standard according to the International Scale (IS). A major molecular response (MMR) is defined as a BCR-ABL/control gene ratio ≤ 0.1% (equal to a 3 log reduction in BCR-ABL transcripts) on the IS. In this study, the control gene was abl.
    Time Frameminimum of 12 cycles (28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS): consists of all patients who passed the screening and are enrolled into the study. Patients may or may not have taken study drug.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants56
    Yes
    1
    12.5%
    2
    28.6%
    No
    4
    50%
    4
    57.1%
    11. Secondary Outcome
    TitleEfficacy Endpoints for Ph+ ALL Patients
    DescriptionBest Response in Ph+ ALL patients was defined as either Complete Remission (CR) with platelet recovery, Complete Remission (CR) with incomplete platelet recovery, Partial Remission (PR) or Stable disease. Stable disease was defined is defined as failure to qualify for either CR, PR, or progressive disease.
    Time Frameminimum of 12 cycles (28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS): consists of all patients who passed the screening and are enrolled into the study. Patients may or may not have taken study drug.
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    Measure Participants31
    Complete Remission with platelet recovery
    2
    25%
    1
    14.3%
    Complete Remission w/incomplete platelet recovery
    0
    0%
    0
    0%
    Partial remission
    0
    0%
    0
    0%
    Stable disease
    1
    12.5%
    0
    0%
    Progressive disease
    0
    0%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group TitleGroup 1Group 2
    Arm/Group Description1 year to < 10 years pediatric patients>= 10 years to <18 years pediatric patients
    All Cause Mortality
    Group 1Group 2
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN)
    Serious Adverse Events
    Group 1Group 2
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/8 (25%) 3/7 (42.9%)
    Blood and lymphatic system disorders
    Neutropenia0/8 (0%) 2/7 (28.6%)
    Gastrointestinal disorders
    Appendix disorder1/8 (12.5%) 0/7 (0%)
    General disorders
    Influenza like illness1/8 (12.5%) 0/7 (0%)
    Pyrexia1/8 (12.5%) 0/7 (0%)
    Renal and urinary disorders
    Renal failure0/8 (0%) 1/7 (14.3%)
    Other (Not Including Serious) Adverse Events
    Group 1Group 2
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total8/8 (100%) 7/7 (100%)
    Blood and lymphatic system disorders
    Haemolytic anaemia0/8 (0%) 1/7 (14.3%)
    Leukopenia0/8 (0%) 1/7 (14.3%)
    Lymphopenia0/8 (0%) 1/7 (14.3%)
    Neutropenia0/8 (0%) 1/7 (14.3%)
    Thrombocytopenia0/8 (0%) 1/7 (14.3%)
    Ear and labyrinth disorders
    Ear pain0/8 (0%) 2/7 (28.6%)
    Gastrointestinal disorders
    Abdominal pain1/8 (12.5%) 2/7 (28.6%)
    Abdominal pain upper1/8 (12.5%) 1/7 (14.3%)
    Constipation0/8 (0%) 1/7 (14.3%)
    Diarrhoea1/8 (12.5%) 3/7 (42.9%)
    Nausea0/8 (0%) 3/7 (42.9%)
    Odynophagia1/8 (12.5%) 0/7 (0%)
    Toothache0/8 (0%) 1/7 (14.3%)
    Vomiting3/8 (37.5%) 3/7 (42.9%)
    General disorders
    Asthenia0/8 (0%) 1/7 (14.3%)
    Catheter site pain1/8 (12.5%) 0/7 (0%)
    Fatigue2/8 (25%) 0/7 (0%)
    Malaise0/8 (0%) 1/7 (14.3%)
    Mucosal inflammation0/8 (0%) 1/7 (14.3%)
    Pyrexia1/8 (12.5%) 1/7 (14.3%)
    Xerosis1/8 (12.5%) 0/7 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia2/8 (25%) 2/7 (28.6%)
    Infections and infestations
    Bronchitis0/8 (0%) 1/7 (14.3%)
    Device related infection1/8 (12.5%) 0/7 (0%)
    Ear infection1/8 (12.5%) 0/7 (0%)
    Folliculitis0/8 (0%) 2/7 (28.6%)
    Fungal skin infection0/8 (0%) 1/7 (14.3%)
    Hand-foot-and-mouth disease1/8 (12.5%) 0/7 (0%)
    Lip infection0/8 (0%) 1/7 (14.3%)
    Nasopharyngitis4/8 (50%) 0/7 (0%)
    Oral candidiasis0/8 (0%) 1/7 (14.3%)
    Otitis media1/8 (12.5%) 0/7 (0%)
    Rhinitis3/8 (37.5%) 1/7 (14.3%)
    Skin infection0/8 (0%) 2/7 (28.6%)
    Tinea pedis0/8 (0%) 1/7 (14.3%)
    Tonsillitis0/8 (0%) 1/7 (14.3%)
    Upper respiratory tract infection1/8 (12.5%) 1/7 (14.3%)
    Investigations
    Alanine aminotransferase increased3/8 (37.5%) 1/7 (14.3%)
    Aspartate aminotransferase increased3/8 (37.5%) 0/7 (0%)
    Bilirubin conjugated increased1/8 (12.5%) 1/7 (14.3%)
    Blood bilirubin increased2/8 (25%) 3/7 (42.9%)
    Blood bilirubin unconjugated increased0/8 (0%) 1/7 (14.3%)
    Blood creatinine increased0/8 (0%) 2/7 (28.6%)
    Blood phosphorus decreased1/8 (12.5%) 0/7 (0%)
    Blood sodium decreased1/8 (12.5%) 0/7 (0%)
    Blood urea increased0/8 (0%) 2/7 (28.6%)
    Blood uric acid increased0/8 (0%) 2/7 (28.6%)
    Electrocardiogram QT prolonged1/8 (12.5%) 0/7 (0%)
    Haematocrit decreased0/8 (0%) 1/7 (14.3%)
    Haemoglobin decreased0/8 (0%) 1/7 (14.3%)
    Neutrophil count increased0/8 (0%) 1/7 (14.3%)
    Platelet count decreased0/8 (0%) 1/7 (14.3%)
    Red blood cell count decreased0/8 (0%) 1/7 (14.3%)
    Weight decreased1/8 (12.5%) 0/7 (0%)
    White blood cell count decreased0/8 (0%) 1/7 (14.3%)
    White blood cell count increased0/8 (0%) 1/7 (14.3%)
    Metabolism and nutrition disorders
    Hypoalbuminaemia1/8 (12.5%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia0/8 (0%) 3/7 (42.9%)
    Back pain1/8 (12.5%) 0/7 (0%)
    Bone pain1/8 (12.5%) 1/7 (14.3%)
    Muscle spasms1/8 (12.5%) 0/7 (0%)
    Musculoskeletal pain1/8 (12.5%) 0/7 (0%)
    Neck pain1/8 (12.5%) 1/7 (14.3%)
    Pain in extremity3/8 (37.5%) 1/7 (14.3%)
    Tendon pain0/8 (0%) 1/7 (14.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma2/8 (25%) 0/7 (0%)
    Nervous system disorders
    Headache4/8 (50%) 2/7 (28.6%)
    Paraesthesia0/8 (0%) 1/7 (14.3%)
    Peripheral sensory neuropathy1/8 (12.5%) 0/7 (0%)
    Presyncope0/8 (0%) 1/7 (14.3%)
    Syncope0/8 (0%) 1/7 (14.3%)
    Reproductive system and breast disorders
    Vulvovaginal pruritus1/8 (12.5%) 0/7 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough2/8 (25%) 2/7 (28.6%)
    Oropharyngeal pain0/8 (0%) 1/7 (14.3%)
    Pharyngeal erythema1/8 (12.5%) 0/7 (0%)
    Productive cough0/8 (0%) 1/7 (14.3%)
    Skin and subcutaneous tissue disorders
    Dermatitis atopic1/8 (12.5%) 0/7 (0%)
    Dry skin0/8 (0%) 2/7 (28.6%)
    Dyshidrotic eczema0/8 (0%) 1/7 (14.3%)
    Eczema2/8 (25%) 1/7 (14.3%)
    Exfoliative rash1/8 (12.5%) 0/7 (0%)
    Psoriasis1/8 (12.5%) 0/7 (0%)
    Rash3/8 (37.5%) 2/7 (28.6%)
    Rash erythematous1/8 (12.5%) 0/7 (0%)
    Rash maculo-papular1/8 (12.5%) 0/7 (0%)
    Rash papular1/8 (12.5%) 0/7 (0%)
    Skin lesion0/8 (0%) 1/7 (14.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    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 or disclosure of trial results in their entirety.

    Results Point of Contact

    Name/TitleStudy Director
    OrganizationNovartis Pharmaceuticals
    Phone82-778-8300
    Emailtrialandresults.registries@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01077544
    Other Study ID Numbers:
    • CAMN107A2120
    • 2010-018419-14
    First Posted:
    Mar 1, 2010
    Last Update Posted:
    Dec 29, 2020
    Last Verified:
    Oct 1, 2020