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NCT00932698 · OUTCOME

AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib

Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma · Source last updated 2019-08-07

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
MEAN
Unit
hr*ng/mL
Interval / dispersion
Standard Deviation
Time frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose

Analysis population: PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point.

Groups in this outcome

Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2

Ixazomib 0.24 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days).

Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2

Ixazomib 0.48 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days).

Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2

Ixazomib 0.8 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days).

Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2

Ixazomib 1.2 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days).

Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2

Ixazomib 1.68 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days).

Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days).

Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2

Ixazomib 2.23 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days).

Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days).

Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days).

Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor.

Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days).

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^23
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^23
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^22
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^22
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^23
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^26
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^23
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^217
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^29
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^26
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21

Reported measurements

Day 1

Analysis denominator · Participants

GroupSource count
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^23
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^22
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^22
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^22
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^23
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^26
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^22
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^212
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^29
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^25
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21
Values in hr*ng/mL · Interval/dispersion: Standard Deviation
GroupValueSpreadLowerUpperComment
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^23.3831.7210Not reportedNot reportedNot reported
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^220.7004.5255Not reportedNot reportedNot reported
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2109.00041.0122Not reportedNot reportedNot reported
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2159.05091.8532Not reportedNot reportedNot reported
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2251.00062.5060Not reportedNot reportedNot reported
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2449.000185.9516Not reportedNot reportedNot reported
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2416.50047.3762Not reportedNot reportedNot reported
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2418.175218.7115Not reportedNot reportedNot reported
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2351.000141.4337Not reportedNot reportedNot reported
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2410.000138.7732Not reportedNot reportedNot reported
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2509.000NANot reportedNot reportedSD was not calculated for 1 participant.
Day 11

Analysis denominator · Participants

GroupSource count
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^23
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^23
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^22
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^21
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^22
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^25
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^22
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^213
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^27
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^25
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21
Values in hr*ng/mL · Interval/dispersion: Standard Deviation
GroupValueSpreadLowerUpperComment
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^256.53315.5095Not reportedNot reportedNot reported
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2177.667115.6820Not reportedNot reportedNot reported
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2458.00042.4264Not reportedNot reportedNot reported
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2605.000NANot reportedNot reportedSD was not calculated for 1 participant.
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2808.500212.8391Not reportedNot reportedNot reported
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21435.6001027.3881Not reportedNot reportedNot reported
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21915.000148.4924Not reportedNot reportedNot reported
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2903.846382.9033Not reportedNot reportedNot reported
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2937.857334.2082Not reportedNot reportedNot reported
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^22297.2001137.8221Not reportedNot reportedNot reported
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21010.000NANot reportedNot reportedSD was not calculated for 1 participant.
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        spread
        1.7210
        value
        3.383
      2. group Id
        OG001
        spread
        4.5255
        value
        20.700
      3. group Id
        OG002
        spread
        41.0122
        value
        109.000
      4. group Id
        OG003
        spread
        91.8532
        value
        159.050
      5. group Id
        OG004
        spread
        62.5060
        value
        251.000
      6. group Id
        OG005
        spread
        185.9516
        value
        449.000
      7. group Id
        OG006
        spread
        47.3762
        value
        416.500
      8. group Id
        OG007
        spread
        218.7115
        value
        418.175
      9. group Id
        OG008
        spread
        141.4337
        value
        351.000
      10. group Id
        OG009
        spread
        138.7732
        value
        410.000
      11. comment
        SD was not calculated for 1 participant.
        group Id
        OG010
        spread
        NA
        value
        509.000
    denoms
    1. counts
      1. group Id
        OG000
        value
        3
      2. group Id
        OG001
        value
        2
      3. group Id
        OG002
        value
        2
      4. group Id
        OG003
        value
        2
      5. group Id
        OG004
        value
        3
      6. group Id
        OG005
        value
        6
      7. group Id
        OG006
        value
        2
      8. group Id
        OG007
        value
        12
      9. group Id
        OG008
        value
        9
      10. group Id
        OG009
        value
        5
      11. group Id
        OG010
        value
        1
      units
      Participants
    title
    Day 1
  2. categories
    1. measurements
      1. group Id
        OG000
        spread
        15.5095
        value
        56.533
      2. group Id
        OG001
        spread
        115.6820
        value
        177.667
      3. group Id
        OG002
        spread
        42.4264
        value
        458.000
      4. comment
        SD was not calculated for 1 participant.
        group Id
        OG003
        spread
        NA
        value
        605.000
      5. group Id
        OG004
        spread
        212.8391
        value
        808.500
      6. group Id
        OG005
        spread
        1027.3881
        value
        1435.600
      7. group Id
        OG006
        spread
        148.4924
        value
        1915.000
      8. group Id
        OG007
        spread
        382.9033
        value
        903.846
      9. group Id
        OG008
        spread
        334.2082
        value
        937.857
      10. group Id
        OG009
        spread
        1137.8221
        value
        2297.200
      11. comment
        SD was not calculated for 1 participant.
        group Id
        OG010
        spread
        NA
        value
        1010.000
    denoms
    1. counts
      1. group Id
        OG000
        value
        3
      2. group Id
        OG001
        value
        3
      3. group Id
        OG002
        value
        2
      4. group Id
        OG003
        value
        1
      5. group Id
        OG004
        value
        2
      6. group Id
        OG005
        value
        5
      7. group Id
        OG006
        value
        2
      8. group Id
        OG007
        value
        13
      9. group Id
        OG008
        value
        7
      10. group Id
        OG009
        value
        5
      11. group Id
        OG010
        value
        1
      units
      Participants
    title
    Day 11
denoms
  1. counts
    1. group Id
      OG000
      value
      3
    2. group Id
      OG001
      value
      3
    3. group Id
      OG002
      value
      2
    4. group Id
      OG003
      value
      2
    5. group Id
      OG004
      value
      3
    6. group Id
      OG005
      value
      6
    7. group Id
      OG006
      value
      3
    8. group Id
      OG007
      value
      17
    9. group Id
      OG008
      value
      9
    10. group Id
      OG009
      value
      6
    11. group Id
      OG010
      value
      1
    units
    Participants
dispersion Type
Standard Deviation
groups
  1. description
    Ixazomib 0.24 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days).
    id
    OG000
    title
    Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2
  2. description
    Ixazomib 0.48 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days).
    id
    OG001
    title
    Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2
  3. description
    Ixazomib 0.8 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days).
    id
    OG002
    title
    Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2
  4. description
    Ixazomib 1.2 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days).
    id
    OG003
    title
    Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2
  5. description
    Ixazomib 1.68 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days).
    id
    OG004
    title
    Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2
  6. description
    Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days).
    id
    OG005
    title
    Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2
  7. description
    Ixazomib 2.23 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days).
    id
    OG006
    title
    Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2
  8. description
    Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days).
    id
    OG007
    title
    Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2
  9. description
    Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days).
    id
    OG008
    title
    Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2
  10. description
    Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determine the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor.
    id
    OG009
    title
    Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2
  11. description
    Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days).
    id
    OG010
    title
    Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2
param Type
MEAN
population Description
PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point.
reporting Status
POSTED
time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
title
AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
type
SECONDARY
unit Of Measure
hr*ng/mL

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Preserved source evidence · Not medical advice