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PANORAMA-1: Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01023308
Collaborator
(none)
767
Enrollment
210
Locations
2
Arms
67.3
Actual Duration (Months)
3.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), inclusive of HDAC6, which disrupts aggresome function, promotes accumulation of cytotoxic misfolded protein aggregates and triggers myeloma cell death. Combination of pan-DAC and protease inhibition by co-treatment with panobinostat (PAN) and bortezomib (BTZ) has demonstrated synergistic cytotoxicity in vitro and in vivo in pre-clinical experiments. Furthermore, clinical experience in advanced multiple myeloma (MM) patients treated by oral panobinostat and i.v bortezomib ± dexamethasone showed very encouraging results for efficacy and manageable toxicity profile.

Given the medical need for improved treatment strategies for patients with previously treated and relapsed MM, the purpose of this prospective, multinational, randomized, double-blind, placebo-controlled, parallel group Phase III study is to compare the results in progression-free survival of 2 combination therapies, panobinostat with bortezomib and dexamethasone or placebo with bortezomib and dexamethasone, in patients with previously treated MM whose disease has recurred or progressed.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
767 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double Blind, Placebo Controlled Phase III Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Actual Study Start Date :
Dec 21, 2009
Actual Primary Completion Date :
Jul 30, 2015
Actual Study Completion Date :
Jul 30, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Panobinostat + Bortezomib + Dexamethasone

Drug: Panobinostat
Panobinostat was administered 3x week ( 2 weeks on 1 week off)
Other Names:
  • LBH589

    • Drug: Bortezomib
    Bortezomib was administered 2 x week ( 2weeks on 1 week off)
    Other Names:
  • (Velcade®)

    • Drug: Dexamethasone
    Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration
    Placebo Comparator: Placebo + Bortezomib + Dexamethasone

    Drug: Bortezomib
    Bortezomib was administered 2 x week ( 2weeks on 1 week off)
    Other Names:
  • (Velcade®)

    • Drug: Dexamethasone
    Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration

    Drug: Placebo
    Placebo was administered 3x week ( 2 weeks on 1 week off)

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival Events in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [45 months]

    2. Progression Free Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [45 months]

    Secondary Outcome Measures

    1. Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone [45 months]

      Number of OS events

    2. Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone [45 months]

      survival time in months

    3. Overall Response Rate in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [45 months]

      Best overall response based on mEBMT criteria per investigator assessment

    4. Time to Response Per Investigator Assessment (mEBMT Criteria) of Response Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [45 months]

    5. Duration of Response Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [45 months]

    6. Time to Progression/Relapse Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [45 months]

    7. European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group [12, 24 and 48 weeks]

      Higher values in the disease symptoms and side effects of treatment scores indicate worsening. Higher scores in the future perspective and body image scores indicate improvement. LS Means and SEM are estimated from the repeated measures model. Following factors and covariates are included in the repeated measurement model: time, treatment, treatment by time interaction, number of prior lines of anti-MM therapy (1/ 2 and 3), prior use of BTZ (Yes/ No), baseline score.Disease Symptom is the sum of 20 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-MY20 have the same score range of 0 -100. Decrease in symptom scores from baseline indicate improvement in symptoms.

    8. European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group [12, 24 and 48 weeks]

      The EORTC QLQ-C30 measures functional dimensions (physical, role, emotional, cognitive, and social), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), six single-item symptom scales (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. Disease Symptom is the sum of 30 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-C30 have the same score range of 0 -100. For global health status and other functional scales,an increase from baseline indicates improvement of QoL. Whereas for symptoms scales, fatigue, dyspnea, insomnia, appetite loss, constipation and diarrhea, decrease in scores from baseline indicate improvement in symptoms.

    9. Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group [12, 24 and 48 weeks]

      Chronic Illness Therapy (FACIT) Measurement System and focuses on four general quality of life domains for physical well being, functional well-being, social/family well-being, and emotional well-being, and includes additional items to characterize treatment-related neurotoxicity. Higher subscales/total scores represent higher QOL. In the case of the neurotoxicity subscale, lower scores correspond to higher neurotoxicity. The recall period referenced in the questionnaire is the past 7 days.Ranges for FACT-G subscales are as follows:.PWB, scale 0 -28, , NtxS scale 0-44, FACT/GOG-Ntx trial outcome index scale is 0-100 and FACT-G scale is also scaled 0-100. An increase from baseline in these scores indicate improvement.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patient has a previous diagnosis of multiple myeloma.

    2. Patient requires retreatment for multiple myeloma

    3. Patient has measurable M component in serum or urine at study screening

    Exclusion Criteria:

    1. Patient who has progressed under all prior lines of anti MM therapy

    2. Patient who has been treated by bortezomib before, and did not reach at least a minor response under this therapy, or progressed under it or within 60 days of last dose

    3. Patient has shown intolerance to bortezomib or to dexamethasone or components of these drugs or has any contraindication to one or the other drug , following locally applicable prescribing information

    4. Patient received prior treatment with DAC inhibitors including panobinostat

    5. Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG

    6. Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pointes

    7. Female patient who is pregnant or breast feeding or with childbearing potential and not willing to use a double method of contraception up to 3 months after the end of study treatment. Male patient who is not willing to use a barrier method of contraception up to 3 months after the end of study treatment.

    Other protocol-defined inclusion/exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Phoenix Arizona United States
    2 Novartis Investigative Site Anaheim California United States 92801
    3 Novartis Investigative Site Concord California United States 94520
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    156 Novartis Investigative Site Seoul Korea, Republic of 03080
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    160 Novartis Investigative Site Beirut Lebanon 6301
    161 Novartis Investigative Site San Luis Potosí Mexico 78218
    162 Novartis Investigative Site Rotterdam Netherlands 3015 CE
    163 Novartis Investigative Site Rotterdam Netherlands
    164 Novartis Investigative Site Utrecht Netherlands 3584 CX
    165 Novartis Investigative Site Bergen Norway NO-5021
    166 Novartis Investigative Site Fredrikstad Norway NO-1603
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    168 Novartis Investigative Site Oslo Norway 0407
    169 Novartis Investigative Site Skien Norway NO-3710
    170 Novartis Investigative Site Trondheim Norway 7006
    171 Novartis Investigative Site Warszawa Poland 02 776
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    173 Novartis Investigative Site Saratov Russian Federation 410028
    174 Novartis Investigative Site St Petersburg Russian Federation 191024
    175 Novartis Investigative Site Singapore Singapore 169608
    176 Novartis Investigative Site Parktown South Africa 2193
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    187 Novartis Investigative Site Barcelona Spain 08041
    188 Novartis Investigative Site Göteborg Sweden SE-413 45
    189 Novartis Investigative Site Linköping Sweden SE-581 85
    190 Novartis Investigative Site Luleå Sweden SE-971 80
    191 Novartis Investigative Site Stockholm Sweden SE-118 83
    192 Novartis Investigative Site Uppsala Sweden SE-751 85
    193 Novartis Investigative Site Kaohsiung City Taiwan 83301
    194 Novartis Investigative Site Taichung Taiwan 40447
    195 Novartis Investigative Site Taipei Taiwan 10048
    196 Novartis Investigative Site Taoyuan Taiwan 333
    197 Novartis Investigative Site Bangkok Thailand 10330
    198 Novartis Investigative Site Bangkok Thailand 10400
    199 Novartis Investigative Site Bangkok Thailand 10700
    200 Novartis Investigative Site Istanbul TUR Turkey 34098
    201 Novartis Investigative Site Adana Turkey 01330
    202 Novartis Investigative Site Ankara Turkey 06100
    203 Novartis Investigative Site Aberdeen Scotland United Kingdom AB25 2ZN
    204 Novartis Investigative Site Glasgow Scotland United Kingdom G12 0YN
    205 Novartis Investigative Site London United Kingdom EC1A 7BE
    206 Novartis Investigative Site London United Kingdom SE5 9RS
    207 Novartis Investigative Site London United Kingdom W12 0HS
    208 Novartis Investigative Site London United Kingdom WC1E 6HX
    209 Novartis Investigative Site Manchester United Kingdom M20 4BX
    210 Novartis Investigative Site Wolverhampton United Kingdom WV10 0QP

    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:
    NCT01023308
    Other Study ID Numbers:
    • CLBH589D2308
    • 2009-015507-52
    First Posted:
    Dec 2, 2009
    Last Update Posted:
    Mar 17, 2020
    Last Verified:
    Mar 1, 2020
    Keywords provided by Novartis Pharmaceuticals
    Myeloma
    DACi
    Bortezomib
    Combination
    Panobinostat
    LBH589D
    relapsed
    Velcade®
    Combination,
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Bortezomib
    Panobinostat

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Period Title: Overall Study
    STARTED 387 381
    COMPLETED 102 102
    NOT COMPLETED 285 279

    Baseline Characteristics

    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib Total
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day. Total of all reporting groups
    Overall Participants 387 381 768
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.4
    (9.34)
    61.8
    (9.43)
    62.1
    (9.38)
    Sex: Female, Male (Count of Participants)
    Female
    185
    47.8%
    176
    46.2%
    361
    47%
    Male
    202
    52.2%
    205
    53.8%
    407
    53%
    Race/Ethnicity, Customized (Number) [Number]
    Caucasian
    249
    64.3%
    250
    65.6%
    499
    65%
    Asian
    128
    33.1%
    104
    27.3%
    232
    30.2%
    Black
    5
    1.3%
    17
    4.5%
    22
    2.9%
    Other
    5
    1.3%
    10
    2.6%
    15
    2%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival Events in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
    Description
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Number [number of events]
    207
    260
    2. Primary Outcome
    Title Progression Free Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
    Description
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Median (95% Confidence Interval) [months]
    11.99
    8.80
    3. Secondary Outcome
    Title Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone
    Description Number of OS events
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Number [Number of OS events]
    134
    152
    4. Secondary Outcome
    Title Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone
    Description survival time in months
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Median (95% Confidence Interval) [months]
    40.28
    35.78
    5. Secondary Outcome
    Title Overall Response Rate in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
    Description Best overall response based on mEBMT criteria per investigator assessment
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Number [% participants with response]
    60.7
    15.7%
    54.6
    14.3%
    6. Secondary Outcome
    Title Time to Response Per Investigator Assessment (mEBMT Criteria) of Response Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
    Description
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Median (95% Confidence Interval) [time to response in months]
    1.51
    2.00
    7. Secondary Outcome
    Title Duration of Response Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
    Description
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Median (95% Confidence Interval) [duration of response in months]
    13.14
    10.87
    8. Secondary Outcome
    Title Time to Progression/Relapse Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
    Description
    Time Frame 45 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Median (95% Confidence Interval) [months]
    12.71
    8.54
    9. Secondary Outcome
    Title European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group
    Description Higher values in the disease symptoms and side effects of treatment scores indicate worsening. Higher scores in the future perspective and body image scores indicate improvement. LS Means and SEM are estimated from the repeated measures model. Following factors and covariates are included in the repeated measurement model: time, treatment, treatment by time interaction, number of prior lines of anti-MM therapy (1/ 2 and 3), prior use of BTZ (Yes/ No), baseline score.Disease Symptom is the sum of 20 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-MY20 have the same score range of 0 -100. Decrease in symptom scores from baseline indicate improvement in symptoms.
    Time Frame 12, 24 and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Disease Symptom wk 12 change baseline (n=215,243)
    -4.795
    -4.865
    Disease Symptom wk 24 change baseline (n=148,177)
    -4.401
    -6.797
    Disease Symptom wk 48 change baseline (n=37,26)
    -2.836
    -6.626
    Side effects of treatment wk 12 chge (n=213,242)
    8.162
    5.524
    Side effects of treatment wk 24 chge (n=148,175)
    9.016
    7.731
    Side effects of treatment wk 48 chge (n=37,26)
    3.357
    3.654
    Future perspective wk 12 chge (n=214,242)
    5.319
    6.194
    Future perspective wk 24 chge (n=148,176)
    3.877
    5.839
    Future perspective wk 48 chge (n=37,26)
    4.331
    6.951
    Body image wk 12 chge (n=213,240)
    -7.178
    -6.22
    Body image wk 24 chge (n=147,175)
    -11.463
    -7.358
    Body image wk 48 chge (n=37,26)
    -2.161
    -4.666
    10. Secondary Outcome
    Title European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group
    Description The EORTC QLQ-C30 measures functional dimensions (physical, role, emotional, cognitive, and social), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), six single-item symptom scales (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. Disease Symptom is the sum of 30 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-C30 have the same score range of 0 -100. For global health status and other functional scales,an increase from baseline indicates improvement of QoL. Whereas for symptoms scales, fatigue, dyspnea, insomnia, appetite loss, constipation and diarrhea, decrease in scores from baseline indicate improvement in symptoms.
    Time Frame 12, 24 and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Global health wk 12 change baseline (n=216,239)
    -9.853
    -4.044
    Global health wk 24 change baseline (n=150,176)
    -7.867
    -1.518
    Global health wk 48 change baseline (n=38,26)
    -2.986
    4.345
    Physical functioning wk 12 chge (n=217,242)
    -9.67
    -5.393
    Physical functioning wk 24 chge (n=151,177)
    -9.516
    -6.456
    Physical functioning wk 48 chge (n=38,26)
    -2.88
    2.037
    Role functioning wk 12 chge (n=215,237)
    -11.159
    -6.762
    Role functioning wk 24 chge (n=150,176)
    -11.875
    -11.263
    Role functioning wk 48 chge (n=38,26)
    -5.927
    -0.401
    Cognitive functioning wk 12 chge (n=216,240)
    -4.464
    -1.023
    Cognitive functioning wk 24 chge (n=149,176)
    -6.053
    -3.542
    Cognitive functioning wk 48 chge (n=38,26)
    -5.568
    -4.042
    Social functioning wk 12 chge (n=216,240)
    -8.502
    -3.991
    Social functioning wk 24 chge (n=148,171)
    -8.925
    -6.338
    Social functioning wk 48 chge (n=37,26)
    -6.104
    4.617
    Fatigue wk 12 chge (n=217,241)
    15.122
    7.939
    Fatigue wk 24 chge (n=151,176)
    12.677
    9.203
    Fatigue wk 48 chge(n=38,26)
    4.646
    -2.625
    Dyspnea wk 12 chge (n=217,240)
    13.964
    6.266
    Dyspnea wk 24 chge (n=151,177)
    7.939
    5.308
    Dyspnea wk 48 chge (n=38,26)
    4.118
    2.82
    Insomnia wk 12 chge (n=216,239)
    6.283
    7.625
    Insomnia wk 24 chge (n=149,176)
    10.023
    6.104
    Insomnia wk 48 chge (n=38,26)
    -2.464
    -3.442
    Appetite loss wk 12 chge (n=217,239)
    15.167
    5.383
    Appetite loss wk 24 chge (n=151,176)
    16.574
    5.861
    Appetite loss wk 48 chge (n=38,26)
    3.999
    -2.963
    Constipation wk 12 chge (n=215,240)
    4.135
    6.42
    Constipation wk 24 chge (n=151,177)
    -0.153
    0.524
    Constipation wk 48 chge (n=38,25)
    -0.358
    -0.946
    Diarrhea wk 12 chge (n=217,241)
    18.888
    10.206
    Diarrhea wk 24 chge (n=150,177)
    23.163
    16.406
    Diarrhea wk 48 chge (n=38,26)
    20.48
    10.996
    11. Secondary Outcome
    Title Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group
    Description Chronic Illness Therapy (FACIT) Measurement System and focuses on four general quality of life domains for physical well being, functional well-being, social/family well-being, and emotional well-being, and includes additional items to characterize treatment-related neurotoxicity. Higher subscales/total scores represent higher QOL. In the case of the neurotoxicity subscale, lower scores correspond to higher neurotoxicity. The recall period referenced in the questionnaire is the past 7 days.Ranges for FACT-G subscales are as follows:.PWB, scale 0 -28, , NtxS scale 0-44, FACT/GOG-Ntx trial outcome index scale is 0-100 and FACT-G scale is also scaled 0-100. An increase from baseline in these scores indicate improvement.
    Time Frame 12, 24 and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Panobinostat + Bortezomib Placebo + Bortezomib
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Measure Participants 387 381
    Neurotoxicity wk 12 change baseline (n=212,240)
    -4.481
    -3.337
    Neurotoxicity wk 24 change baseline (n=148,174)
    -4.564
    -4.739
    Neurotoxicity wk 48 change baseline (n=35,26)
    -3.158
    -2.133
    Physical wellbeing wk 12 chge (n=215,240)
    -3.29
    -1.952
    Physical wellbeingwk 24 chge (n=150,176)
    -3.044
    -2.259
    Physical wellbeing wk 48 chge (n=38,26)
    -2.037
    0.203
    Trial Outcomes wk 12 chge (n=209,236)
    -10.573
    -6.874
    Trial Outcomes wk 24 chge (n=148,173)
    -9.84
    -8.894
    Trial Outcomes wk 48 chge (n=35,26)
    -6.633
    -2.821
    FACT-G Total wk 12 chge (n=213,240)
    -6.658
    -4.106
    FACT-G Totalwk 24 chge (n=147,175)
    -6.076
    -4.609
    FACT-G Total wk 48 chge (n=37,26)
    -2.704
    -1.435
    FACT/GOGNTX Total wk 12 chge (n=206,230)
    -11.176
    -7.524
    FACT/GOGNTX Total wk 24 chge (n=146,172)
    -10.581
    -9.179
    FACT/GOGNTX Total wk 48 chge (n=35,26)
    -5.871
    -3.151

    Adverse Events

    Time Frame Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
    Adverse Event Reporting Description
    Arm/Group Title PAN+BTZ PBO+BTZ
    Arm/Group Description Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day. Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day..
    All Cause Mortality
    PAN+BTZ PBO+BTZ
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    PAN+BTZ PBO+BTZ
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 228/381 (59.8%) 157/377 (41.6%)
    Blood and lymphatic system disorders
    Anaemia 14/381 (3.7%) 3/377 (0.8%)
    Febrile neutropenia 3/381 (0.8%) 1/377 (0.3%)
    Hyperviscosity syndrome 0/381 (0%) 1/377 (0.3%)
    Leukocytosis 1/381 (0.3%) 0/377 (0%)
    Leukopenia 2/381 (0.5%) 0/377 (0%)
    Monocytosis 1/381 (0.3%) 0/377 (0%)
    Neutropenia 2/381 (0.5%) 1/377 (0.3%)
    Pancytopenia 1/381 (0.3%) 1/377 (0.3%)
    Thrombocytopenia 28/381 (7.3%) 8/377 (2.1%)
    Cardiac disorders
    Acute coronary syndrome 1/381 (0.3%) 0/377 (0%)
    Acute myocardial infarction 1/381 (0.3%) 0/377 (0%)
    Angina pectoris 2/381 (0.5%) 2/377 (0.5%)
    Atrial fibrillation 4/381 (1%) 2/377 (0.5%)
    Atrial flutter 0/381 (0%) 1/377 (0.3%)
    Bradycardia 2/381 (0.5%) 0/377 (0%)
    Cardiac arrest 2/381 (0.5%) 2/377 (0.5%)
    Cardiac failure 1/381 (0.3%) 1/377 (0.3%)
    Cardiac failure acute 1/381 (0.3%) 0/377 (0%)
    Cardiac failure congestive 0/381 (0%) 1/377 (0.3%)
    Cardio-respiratory arrest 0/381 (0%) 1/377 (0.3%)
    Cardiopulmonary failure 0/381 (0%) 1/377 (0.3%)
    Left ventricular dysfunction 0/381 (0%) 1/377 (0.3%)
    Myocardial infarction 2/381 (0.5%) 0/377 (0%)
    Myocardial ischaemia 2/381 (0.5%) 0/377 (0%)
    Pericardial effusion 0/381 (0%) 1/377 (0.3%)
    Sinus tachycardia 1/381 (0.3%) 0/377 (0%)
    Tachycardia 2/381 (0.5%) 0/377 (0%)
    Ventricular tachycardia 1/381 (0.3%) 0/377 (0%)
    Ear and labyrinth disorders
    Vertigo 1/381 (0.3%) 0/377 (0%)
    Eye disorders
    Conjunctivitis 1/381 (0.3%) 0/377 (0%)
    Exophthalmos 1/381 (0.3%) 0/377 (0%)
    Optic ischaemic neuropathy 1/381 (0.3%) 0/377 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 1/381 (0.3%) 0/377 (0%)
    Abdominal distension 1/381 (0.3%) 0/377 (0%)
    Abdominal pain 3/381 (0.8%) 3/377 (0.8%)
    Abdominal pain upper 1/381 (0.3%) 0/377 (0%)
    Colitis 3/381 (0.8%) 0/377 (0%)
    Constipation 3/381 (0.8%) 3/377 (0.8%)
    Diarrhoea 43/381 (11.3%) 9/377 (2.4%)
    Dysphagia 1/381 (0.3%) 0/377 (0%)
    Faecaloma 1/381 (0.3%) 0/377 (0%)
    Gastric haemorrhage 2/381 (0.5%) 0/377 (0%)
    Gastritis 2/381 (0.5%) 0/377 (0%)
    Gastrointestinal haemorrhage 2/381 (0.5%) 3/377 (0.8%)
    Gastrooesophageal reflux disease 1/381 (0.3%) 0/377 (0%)
    Haematemesis 1/381 (0.3%) 0/377 (0%)
    Haematochezia 2/381 (0.5%) 0/377 (0%)
    Haemorrhoids 0/381 (0%) 1/377 (0.3%)
    Ileus 5/381 (1.3%) 3/377 (0.8%)
    Ileus paralytic 0/381 (0%) 1/377 (0.3%)
    Inguinal hernia 2/381 (0.5%) 1/377 (0.3%)
    Intestinal ischaemia 1/381 (0.3%) 0/377 (0%)
    Large intestine perforation 1/381 (0.3%) 0/377 (0%)
    Nausea 7/381 (1.8%) 0/377 (0%)
    Necrotising oesophagitis 1/381 (0.3%) 0/377 (0%)
    Pancreatitis 1/381 (0.3%) 0/377 (0%)
    Pancreatitis acute 2/381 (0.5%) 1/377 (0.3%)
    Peritoneal necrosis 1/381 (0.3%) 0/377 (0%)
    Rectal haemorrhage 1/381 (0.3%) 0/377 (0%)
    Subileus 1/381 (0.3%) 1/377 (0.3%)
    Upper gastrointestinal haemorrhage 2/381 (0.5%) 0/377 (0%)
    Vomiting 12/381 (3.1%) 3/377 (0.8%)
    General disorders
    Asthenia 15/381 (3.9%) 6/377 (1.6%)
    Chest discomfort 1/381 (0.3%) 1/377 (0.3%)
    Chills 1/381 (0.3%) 0/377 (0%)
    Fatigue 11/381 (2.9%) 2/377 (0.5%)
    General physical health deterioration 2/381 (0.5%) 0/377 (0%)
    Generalised oedema 1/381 (0.3%) 0/377 (0%)
    Hypothermia 0/381 (0%) 2/377 (0.5%)
    Multi-organ failure 1/381 (0.3%) 1/377 (0.3%)
    Non-cardiac chest pain 1/381 (0.3%) 3/377 (0.8%)
    Oedema peripheral 1/381 (0.3%) 0/377 (0%)
    Pyrexia 16/381 (4.2%) 11/377 (2.9%)
    Spinal pain 0/381 (0%) 1/377 (0.3%)
    Sudden death 1/381 (0.3%) 1/377 (0.3%)
    Hepatobiliary disorders
    Biliary dyskinesia 0/381 (0%) 1/377 (0.3%)
    Cholecystitis 1/381 (0.3%) 1/377 (0.3%)
    Hepatic cirrhosis 1/381 (0.3%) 0/377 (0%)
    Hepatic failure 1/381 (0.3%) 0/377 (0%)
    Hepatomegaly 1/381 (0.3%) 1/377 (0.3%)
    Hyperbilirubinaemia 0/381 (0%) 1/377 (0.3%)
    Jaundice 0/381 (0%) 1/377 (0.3%)
    Infections and infestations
    Acute tonsillitis 1/381 (0.3%) 0/377 (0%)
    Appendicitis 1/381 (0.3%) 0/377 (0%)
    Aspergillosis 1/381 (0.3%) 0/377 (0%)
    Atypical pneumonia 1/381 (0.3%) 0/377 (0%)
    Bacteraemia 0/381 (0%) 1/377 (0.3%)
    Bacteriuria 1/381 (0.3%) 0/377 (0%)
    Bronchitis 3/381 (0.8%) 2/377 (0.5%)
    Bronchopneumonia 1/381 (0.3%) 1/377 (0.3%)
    Bronchopulmonary aspergillosis 1/381 (0.3%) 0/377 (0%)
    Cellulitis 2/381 (0.5%) 1/377 (0.3%)
    Clostridium difficile colitis 2/381 (0.5%) 0/377 (0%)
    Cytomegalovirus colitis 1/381 (0.3%) 0/377 (0%)
    Device related infection 0/381 (0%) 1/377 (0.3%)
    Device related sepsis 1/381 (0.3%) 0/377 (0%)
    Disseminated tuberculosis 1/381 (0.3%) 0/377 (0%)
    Diverticulitis 1/381 (0.3%) 0/377 (0%)
    Enteritis infectious 1/381 (0.3%) 0/377 (0%)
    Erysipelas 0/381 (0%) 1/377 (0.3%)
    Escherichia urinary tract infection 0/381 (0%) 1/377 (0.3%)
    Gastroenteritis 7/381 (1.8%) 2/377 (0.5%)
    Gastroenteritis salmonella 2/381 (0.5%) 0/377 (0%)
    Gastrointestinal infection 1/381 (0.3%) 0/377 (0%)
    Haemophilus sepsis 0/381 (0%) 1/377 (0.3%)
    Hepatitis B 3/381 (0.8%) 1/377 (0.3%)
    Herpes zoster 4/381 (1%) 5/377 (1.3%)
    Infection 5/381 (1.3%) 2/377 (0.5%)
    Influenza 1/381 (0.3%) 1/377 (0.3%)
    Lobar pneumonia 2/381 (0.5%) 0/377 (0%)
    Lower respiratory tract infection 3/381 (0.8%) 3/377 (0.8%)
    Lung infection 2/381 (0.5%) 2/377 (0.5%)
    Nasopharyngitis 0/381 (0%) 1/377 (0.3%)
    Necrotising fasciitis 0/381 (0%) 2/377 (0.5%)
    Neutropenic sepsis 2/381 (0.5%) 1/377 (0.3%)
    Oral candidiasis 0/381 (0%) 1/377 (0.3%)
    Parotitis 1/381 (0.3%) 0/377 (0%)
    Periodontitis 1/381 (0.3%) 0/377 (0%)
    Pharyngitis 2/381 (0.5%) 1/377 (0.3%)
    Pneumococcal sepsis 1/381 (0.3%) 0/377 (0%)
    Pneumonia 56/381 (14.7%) 40/377 (10.6%)
    Pneumonia bacterial 0/381 (0%) 2/377 (0.5%)
    Pneumonia fungal 2/381 (0.5%) 0/377 (0%)
    Pneumonia haemophilus 0/381 (0%) 1/377 (0.3%)
    Pneumonia influenzal 2/381 (0.5%) 1/377 (0.3%)
    Pneumonia pneumococcal 0/381 (0%) 1/377 (0.3%)
    Pneumonia respiratory syncytial viral 0/381 (0%) 1/377 (0.3%)
    Pseudomonal bacteraemia 1/381 (0.3%) 0/377 (0%)
    Pulmonary tuberculosis 1/381 (0.3%) 1/377 (0.3%)
    Respiratory tract infection 4/381 (1%) 2/377 (0.5%)
    Salmonellosis 0/381 (0%) 1/377 (0.3%)
    Sepsis 9/381 (2.4%) 7/377 (1.9%)
    Septic shock 9/381 (2.4%) 2/377 (0.5%)
    Sinusitis 1/381 (0.3%) 1/377 (0.3%)
    Skin infection 1/381 (0.3%) 0/377 (0%)
    Staphylococcal sepsis 0/381 (0%) 1/377 (0.3%)
    Streptococcal sepsis 0/381 (0%) 1/377 (0.3%)
    Upper respiratory tract infection 4/381 (1%) 3/377 (0.8%)
    Urinary tract infection 8/381 (2.1%) 4/377 (1.1%)
    Varicella 1/381 (0.3%) 0/377 (0%)
    Viral haemorrhagic cystitis 0/381 (0%) 1/377 (0.3%)
    Viral infection 1/381 (0.3%) 0/377 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 1/381 (0.3%) 0/377 (0%)
    Contusion 0/381 (0%) 1/377 (0.3%)
    Fall 2/381 (0.5%) 0/377 (0%)
    Femoral neck fracture 1/381 (0.3%) 1/377 (0.3%)
    Femur fracture 0/381 (0%) 1/377 (0.3%)
    Hand fracture 1/381 (0.3%) 0/377 (0%)
    Humerus fracture 0/381 (0%) 1/377 (0.3%)
    Intentional overdose 1/381 (0.3%) 0/377 (0%)
    Laceration 1/381 (0.3%) 0/377 (0%)
    Overdose 3/381 (0.8%) 0/377 (0%)
    Pelvic fracture 1/381 (0.3%) 0/377 (0%)
    Rib fracture 0/381 (0%) 1/377 (0.3%)
    Tibia fracture 1/381 (0.3%) 0/377 (0%)
    Transfusion reaction 1/381 (0.3%) 0/377 (0%)
    Investigations
    Alanine aminotransferase increased 1/381 (0.3%) 1/377 (0.3%)
    Aspartate aminotransferase increased 1/381 (0.3%) 1/377 (0.3%)
    Blood creatinine increased 1/381 (0.3%) 2/377 (0.5%)
    Blood lactate dehydrogenase increased 0/381 (0%) 1/377 (0.3%)
    Blood potassium decreased 0/381 (0%) 1/377 (0.3%)
    Blood pressure decreased 0/381 (0%) 1/377 (0.3%)
    C-reactive protein increased 2/381 (0.5%) 0/377 (0%)
    Gamma-glutamyltransferase increased 0/381 (0%) 2/377 (0.5%)
    General physical condition abnormal 1/381 (0.3%) 0/377 (0%)
    Platelet count decreased 4/381 (1%) 0/377 (0%)
    Weight decreased 0/381 (0%) 1/377 (0.3%)
    White blood cell count decreased 1/381 (0.3%) 0/377 (0%)
    Metabolism and nutrition disorders
    Acidosis 0/381 (0%) 1/377 (0.3%)
    Decreased appetite 4/381 (1%) 2/377 (0.5%)
    Dehydration 11/381 (2.9%) 5/377 (1.3%)
    Diabetes mellitus 0/381 (0%) 1/377 (0.3%)
    Diabetes mellitus inadequate control 1/381 (0.3%) 0/377 (0%)
    Electrolyte imbalance 1/381 (0.3%) 0/377 (0%)
    Hypercalcaemia 1/381 (0.3%) 3/377 (0.8%)
    Hyperglycaemia 2/381 (0.5%) 3/377 (0.8%)
    Hypocalcaemia 1/381 (0.3%) 0/377 (0%)
    Hypochloraemia 1/381 (0.3%) 0/377 (0%)
    Hypoglycaemia 1/381 (0.3%) 2/377 (0.5%)
    Hypokalaemia 8/381 (2.1%) 4/377 (1.1%)
    Hyponatraemia 4/381 (1%) 1/377 (0.3%)
    Hypophagia 2/381 (0.5%) 0/377 (0%)
    Hypophosphataemia 1/381 (0.3%) 0/377 (0%)
    Metabolic acidosis 0/381 (0%) 1/377 (0.3%)
    Tumour lysis syndrome 1/381 (0.3%) 0/377 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/381 (0.5%) 0/377 (0%)
    Back pain 3/381 (0.8%) 2/377 (0.5%)
    Bone pain 1/381 (0.3%) 1/377 (0.3%)
    Bursitis 1/381 (0.3%) 0/377 (0%)
    Flank pain 1/381 (0.3%) 0/377 (0%)
    Joint swelling 1/381 (0.3%) 0/377 (0%)
    Muscular weakness 0/381 (0%) 1/377 (0.3%)
    Musculoskeletal pain 1/381 (0.3%) 1/377 (0.3%)
    Myalgia 2/381 (0.5%) 0/377 (0%)
    Myopathy 1/381 (0.3%) 0/377 (0%)
    Osteonecrosis of jaw 1/381 (0.3%) 0/377 (0%)
    Pain in extremity 1/381 (0.3%) 1/377 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/381 (0%) 1/377 (0.3%)
    Endometrial cancer 1/381 (0.3%) 0/377 (0%)
    Prostate cancer 0/381 (0%) 1/377 (0.3%)
    Rectal cancer 0/381 (0%) 1/377 (0.3%)
    Small cell lung cancer 0/381 (0%) 2/377 (0.5%)
    Nervous system disorders
    Altered state of consciousness 1/381 (0.3%) 0/377 (0%)
    Autonomic neuropathy 1/381 (0.3%) 0/377 (0%)
    Brain compression 0/381 (0%) 1/377 (0.3%)
    Brain injury 0/381 (0%) 1/377 (0.3%)
    Brain oedema 1/381 (0.3%) 0/377 (0%)
    Central nervous system haemorrhage 0/381 (0%) 1/377 (0.3%)
    Central nervous system necrosis 1/381 (0.3%) 0/377 (0%)
    Cerebral haemorrhage 1/381 (0.3%) 2/377 (0.5%)
    Cerebrovascular accident 3/381 (0.8%) 0/377 (0%)
    Coma 1/381 (0.3%) 0/377 (0%)
    Convulsion 1/381 (0.3%) 0/377 (0%)
    Cranial nerve paralysis 0/381 (0%) 1/377 (0.3%)
    Depressed level of consciousness 1/381 (0.3%) 0/377 (0%)
    Dizziness 5/381 (1.3%) 2/377 (0.5%)
    Haemorrhage intracranial 1/381 (0.3%) 0/377 (0%)
    Headache 1/381 (0.3%) 0/377 (0%)
    Hemiparesis 1/381 (0.3%) 1/377 (0.3%)
    Hyperreflexia 0/381 (0%) 1/377 (0.3%)
    Lacunar infarction 1/381 (0.3%) 1/377 (0.3%)
    Loss of consciousness 5/381 (1.3%) 1/377 (0.3%)
    Neuralgia 1/381 (0.3%) 1/377 (0.3%)
    Neuropathy peripheral 3/381 (0.8%) 1/377 (0.3%)
    Paraparesis 1/381 (0.3%) 0/377 (0%)
    Paraplegia 0/381 (0%) 1/377 (0.3%)
    Polyneuropathy 0/381 (0%) 1/377 (0.3%)
    Post herpetic neuralgia 0/381 (0%) 1/377 (0.3%)
    Sciatica 0/381 (0%) 1/377 (0.3%)
    Sensory loss 0/381 (0%) 1/377 (0.3%)
    Somnolence 1/381 (0.3%) 0/377 (0%)
    Speech disorder 0/381 (0%) 1/377 (0.3%)
    Syncope 5/381 (1.3%) 2/377 (0.5%)
    Transient ischaemic attack 1/381 (0.3%) 0/377 (0%)
    VIIth nerve paralysis 0/381 (0%) 1/377 (0.3%)
    Psychiatric disorders
    Confusional state 1/381 (0.3%) 1/377 (0.3%)
    Delirium 1/381 (0.3%) 0/377 (0%)
    Hypomania 1/381 (0.3%) 0/377 (0%)
    Mental disorder 0/381 (0%) 1/377 (0.3%)
    Mental status changes 1/381 (0.3%) 0/377 (0%)
    Renal and urinary disorders
    Anuria 0/381 (0%) 1/377 (0.3%)
    Azotaemia 0/381 (0%) 1/377 (0.3%)
    Oliguria 1/381 (0.3%) 0/377 (0%)
    Renal failure 4/381 (1%) 4/377 (1.1%)
    Renal failure acute 7/381 (1.8%) 9/377 (2.4%)
    Renal impairment 1/381 (0.3%) 1/377 (0.3%)
    Ureteric obstruction 1/381 (0.3%) 0/377 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 1/381 (0.3%) 0/377 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/381 (0%) 2/377 (0.5%)
    Acute respiratory failure 3/381 (0.8%) 1/377 (0.3%)
    Aspiration 0/381 (0%) 1/377 (0.3%)
    Asthma 0/381 (0%) 1/377 (0.3%)
    Chronic obstructive pulmonary disease 0/381 (0%) 1/377 (0.3%)
    Cough 1/381 (0.3%) 0/377 (0%)
    Dyspnoea 4/381 (1%) 7/377 (1.9%)
    Epistaxis 2/381 (0.5%) 1/377 (0.3%)
    Hypoventilation 0/381 (0%) 1/377 (0.3%)
    Hypoxia 1/381 (0.3%) 0/377 (0%)
    Lung disorder 1/381 (0.3%) 1/377 (0.3%)
    Lung infiltration 1/381 (0.3%) 0/377 (0%)
    Orthopnoea 1/381 (0.3%) 1/377 (0.3%)
    Pleural effusion 4/381 (1%) 0/377 (0%)
    Pneumonitis 1/381 (0.3%) 3/377 (0.8%)
    Pneumothorax 1/381 (0.3%) 0/377 (0%)
    Pulmonary embolism 4/381 (1%) 4/377 (1.1%)
    Pulmonary haemorrhage 1/381 (0.3%) 0/377 (0%)
    Pulmonary hypertension 1/381 (0.3%) 0/377 (0%)
    Pulmonary oedema 1/381 (0.3%) 1/377 (0.3%)
    Respiratory distress 1/381 (0.3%) 0/377 (0%)
    Respiratory failure 5/381 (1.3%) 0/377 (0%)
    Tachypnoea 0/381 (0%) 1/377 (0.3%)
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis 1/381 (0.3%) 1/377 (0.3%)
    Dermatitis allergic 0/381 (0%) 1/377 (0.3%)
    Rash 2/381 (0.5%) 1/377 (0.3%)
    Swelling face 1/381 (0.3%) 0/377 (0%)
    Vascular disorders
    Aortic stenosis 1/381 (0.3%) 0/377 (0%)
    Circulatory collapse 2/381 (0.5%) 0/377 (0%)
    Deep vein thrombosis 2/381 (0.5%) 3/377 (0.8%)
    Embolism 1/381 (0.3%) 0/377 (0%)
    Haematoma 1/381 (0.3%) 0/377 (0%)
    Hypotension 5/381 (1.3%) 2/377 (0.5%)
    Hypovolaemic shock 3/381 (0.8%) 0/377 (0%)
    Lymphoedema 0/381 (0%) 1/377 (0.3%)
    Orthostatic hypotension 9/381 (2.4%) 1/377 (0.3%)
    Shock haemorrhagic 1/381 (0.3%) 0/377 (0%)
    Venous thrombosis limb 1/381 (0.3%) 1/377 (0.3%)
    Other (Not Including Serious) Adverse Events
    PAN+BTZ PBO+BTZ
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 379/381 (99.5%) 366/377 (97.1%)
    Blood and lymphatic system disorders
    Anaemia 154/381 (40.4%) 125/377 (33.2%)
    Leukopenia 61/381 (16%) 31/377 (8.2%)
    Lymphopenia 52/381 (13.6%) 35/377 (9.3%)
    Neutropenia 112/381 (29.4%) 40/377 (10.6%)
    Thrombocytopenia 238/381 (62.5%) 150/377 (39.8%)
    Eye disorders
    Conjunctivitis 28/381 (7.3%) 31/377 (8.2%)
    Gastrointestinal disorders
    Abdominal distension 30/381 (7.9%) 25/377 (6.6%)
    Abdominal pain 50/381 (13.1%) 38/377 (10.1%)
    Abdominal pain upper 43/381 (11.3%) 36/377 (9.5%)
    Constipation 101/381 (26.5%) 122/377 (32.4%)
    Diarrhoea 254/381 (66.7%) 155/377 (41.1%)
    Dyspepsia 47/381 (12.3%) 43/377 (11.4%)
    Nausea 137/381 (36%) 78/377 (20.7%)
    Vomiting 91/381 (23.9%) 47/377 (12.5%)
    General disorders
    Asthenia 77/381 (20.2%) 51/377 (13.5%)
    Fatigue 155/381 (40.7%) 109/377 (28.9%)
    Oedema peripheral 108/381 (28.3%) 72/377 (19.1%)
    Pyrexia 90/381 (23.6%) 48/377 (12.7%)
    Infections and infestations
    Bronchitis 20/381 (5.2%) 25/377 (6.6%)
    Herpes zoster 15/381 (3.9%) 36/377 (9.5%)
    Nasopharyngitis 49/381 (12.9%) 46/377 (12.2%)
    Respiratory tract infection 17/381 (4.5%) 20/377 (5.3%)
    Upper respiratory tract infection 65/381 (17.1%) 53/377 (14.1%)
    Urinary tract infection 23/381 (6%) 15/377 (4%)
    Investigations
    Alanine aminotransferase increased 22/381 (5.8%) 19/377 (5%)
    Blood creatinine increased 37/381 (9.7%) 21/377 (5.6%)
    Blood urea increased 20/381 (5.2%) 10/377 (2.7%)
    Platelet count decreased 43/381 (11.3%) 17/377 (4.5%)
    Weight decreased 44/381 (11.5%) 17/377 (4.5%)
    Metabolism and nutrition disorders
    Decreased appetite 106/381 (27.8%) 46/377 (12.2%)
    Hyperglycaemia 30/381 (7.9%) 25/377 (6.6%)
    Hypoalbuminaemia 21/381 (5.5%) 8/377 (2.1%)
    Hypocalcaemia 35/381 (9.2%) 32/377 (8.5%)
    Hypokalaemia 100/381 (26.2%) 52/377 (13.8%)
    Hyponatraemia 48/381 (12.6%) 18/377 (4.8%)
    Hypophosphataemia 42/381 (11%) 32/377 (8.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 25/381 (6.6%) 26/377 (6.9%)
    Back pain 45/381 (11.8%) 46/377 (12.2%)
    Bone pain 21/381 (5.5%) 31/377 (8.2%)
    Muscle spasms 23/381 (6%) 21/377 (5.6%)
    Muscular weakness 24/381 (6.3%) 20/377 (5.3%)
    Myalgia 24/381 (6.3%) 24/377 (6.4%)
    Pain in extremity 40/381 (10.5%) 54/377 (14.3%)
    Nervous system disorders
    Dizziness 67/381 (17.6%) 61/377 (16.2%)
    Dysgeusia 36/381 (9.4%) 26/377 (6.9%)
    Headache 51/381 (13.4%) 40/377 (10.6%)
    Hypoaesthesia 28/381 (7.3%) 34/377 (9%)
    Neuralgia 38/381 (10%) 44/377 (11.7%)
    Neuropathy peripheral 117/381 (30.7%) 133/377 (35.3%)
    Paraesthesia 24/381 (6.3%) 27/377 (7.2%)
    Peripheral sensory neuropathy 42/381 (11%) 46/377 (12.2%)
    Polyneuropathy 28/381 (7.3%) 28/377 (7.4%)
    Psychiatric disorders
    Insomnia 73/381 (19.2%) 61/377 (16.2%)
    Respiratory, thoracic and mediastinal disorders
    Cough 81/381 (21.3%) 70/377 (18.6%)
    Dyspnoea 53/381 (13.9%) 40/377 (10.6%)
    Skin and subcutaneous tissue disorders
    Rash 33/381 (8.7%) 23/377 (6.1%)
    Vascular disorders
    Hypertension 27/381 (7.1%) 23/377 (6.1%)
    Hypotension 49/381 (12.9%) 34/377 (9%)
    Orthostatic hypotension 22/381 (5.8%) 11/377 (2.9%)

    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 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
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01023308
    Other Study ID Numbers:
    • CLBH589D2308
    • 2009-015507-52
    First Posted:
    Dec 2, 2009
    Last Update Posted:
    Mar 17, 2020
    Last Verified:
    Mar 1, 2020