Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Bortezomib, Velcade
Brief summary
The purpose of this post marketing study is to determine the plasma concentration of bortezomib (unchanged drug) to assess the pharmacokinetic (PK - the study of the way a drug enters and leaves the blood and tissues over time) properties in the Taiwanese population. It will also provide expanded access (expanded access, sometimes called compassionate use, is the use of an investigational drug outside of a clinical trial to treat a participant with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options) to bortezomib for the same group of participants with multiple myeloma (cancer of the types of cells normally found in bone marrow).
Detailed description
This is an open-label (all people know the identity of the intervention), single-arm, multi-center (conducted in more than 1 center) study to assess the PK of bortezomib and to provide expanded access to bortezomib for 14 Taiwanese participants with multiple myeloma who have received at least 2 previous lines of therapy (medicine or medical care given to a participant for a disease or condition) and are refractory (not responding to treatment) to or have relapsed (the return of a medical problem) after their last therapy. Eligible participants will receive bortezomib 1.3 milligram (mg) per meter square (m\^2) on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. Blood samples for PK assessment will be collected on specified time points of Day 1, Day 8, and Day 11 of Cycle 1. Efficacy of the participants will primarily be evaluated by recording 'response to treatment' and 'Karnofsky Performance Status'. Participants' safety will be monitored throughout the study.
Interventions
DRUGBortezomib
Bortezomib 1.3 mg per (m\^2) on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles.
Sponsors
Johnson & Johnson Taiwan Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants previously diagnosed with multiple myeloma based on standard criteria * Participant has received at least 2 previous lines of therapy for multiple myeloma and, in the Investigator's opinion, currently requires therapy because of relapsed (the return of a medical problem) or progressive disease * Female participants either postmenopausal or surgically sterilized or willing to use an acceptable method of birth control from Screening through the Final Visit * If male, the participant agrees to use an acceptable barrier method for contraception from Screening through the Final Visit * Participant has a Karnofsky performance status classifies participants as to their functional impairment and is used to compare effectiveness of different therapies and to assess the prognosis \[outlook, probable outcomes\] in individual participants) greater than 60
Exclusion criteria
* If the participant received bortezomib in a previous trial, the Participants' best response to bortezomib must be progressive disease * If the participant received bortezomib in a previous trial, the participant must have experienced 1 or more serious adverse events * Participants who have received nitrosoureas within 6 weeks or any other chemotherapy (treatment of disease, usually cancer, by chemical agents) within 3 weeks before enrollment * Participants who have received corticosteroids (greater than 10 milligram per day prednisone or equivalent) within 3 weeks before enrollment * Human Immunodeficiency Virus (HIV - a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person)-positive or hepatitis-B surface antigen-positive participants or participants with known active hepatitis-C infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response to Treatment at Day 1 of Cycle 5 | Day 1 of Cycle 5 | Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression. |
| Number of Participants With Response to Treatment at Day 1 of Cycle 7 | Day 1 of Cycle 7 | Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression. |
| Number of Participants With Response to Treatment at Day 11 of Cycle 8 | Day 11 of Cycle 8 | Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression. |
| Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline | Baseline | The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses. |
| Number of Participants With KPS Score at Day 1 of Cycle 1 | Day 1 of Cycle 1 | The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses. |
| Number of Participants With KPS Score at Day 1 of Cycle 3 | Day 1 of Cycle 3 | The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses. |
| Number of Participants With KPS Score at Day 1 of Cycle 5 | Day 1 of Cycle 5 | The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses. |
| Number of Participants With KPS Score at Day 1 of Cycle 7 | Day 1 of Cycle 7 | The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses. |
| Number of Participants With KPS Score at Day 11 of Cycle 8 | Day 11 of Cycle 8 | The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses. |
| Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile. |
| Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile. |
| Elimination Half-Life Period (T1/2) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | The T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda\[z\]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). |
| Elimination Half-Life Period (T1/2) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | The T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda\[z\]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). |
| Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points. |
| Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | The AUC(0-t) is area under the plasma concentration-time curve from time zero to the last quantifiable concentration determined by the trapezoidal rule. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | The AUC(0-t) is area under the plasma concentration-time curve from zero to the last quantifiable concentration determined by the trapezoidal rule. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 1 of Cycle 1 | Day 1 of Cycle 1 | The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration. |
| Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | AUMC is defined as the area under first moment plasma concentration-time curve from time of dosing up to definite time t, to infinity, or to the time of last measurable concentration determined by the following equation: AUMC(0 to infinity)=Cntn/k elimination(el) + Cn/k(el\^2) summation\[(tn - tn\^-1) (Cn\^-1) (tn\^-1)\] + Cntn/2 where Cn=last quantifiable concentration, tn=time at which Cn is measured, k=rate constant. |
| Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | AUMC is defined as the area under first moment plasma concentration-time curve from time of dosing up to definite time t, to infinity, or to the time of last measurable concentration determined by the following equation: AUMC(0 to infinity)=Cntn/k elimination(el) + Cn/k(el\^2) summation\[(tn - tn\^-1) (Cn\^-1) (tn\^-1)\] + Cntn/2 where Cn=last quantifiable concentration, tn=time at which Cn is measured, k=rate constant. |
| Mean Residence Time (MRT) of Bortezomib in the Body on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | The MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(infinity)/AUC(infinity) where AUMC(infinity) is area under the plasma concentration-time first moment curve from time zero to infinite time and AUC(infinity) is the area under the plasma concentration-time curve from time zero to infinite time. |
| Mean Residence Time (MRT) of Bortezomib in the Body on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | The MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(infinity)/AUC(infinity) where AUMC(infinity) is area under the plasma concentration-time first moment curve from time zero to infinite time and AUC(infinity) is the area under the plasma concentration-time curve from time zero to infinite time. |
| Systemic Clearance (CL) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-infinity). |
| Systemic Clearance (CL) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-infinity). |
| Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 1 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC\[0-infinity\])\*(AUMC\[0-infinity\])/AUC\[0-infinity\]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time. |
| Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 11 of Cycle 1 | 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC\[0-infinity\])\*(AUMC\[0-infinity\])/AUC\[0-infinity\]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib Participants received 1.3 mg per m\^2 of bortezomib on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Progressive disease | 4 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Bortezomib |
|---|---|
| Age Continuous | 62.63 Years STANDARD_DEVIATION 8.31 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 14 / 14 |
Outcome results
Primary
Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 11 of Cycle 1
AUMC is defined as the area under first moment plasma concentration-time curve from time of dosing up to definite time t, to infinity, or to the time of last measurable concentration determined by the following equation: AUMC(0 to infinity)=Cntn/k elimination(el) + Cn/k(el\^2) summation\[(tn - tn\^-1) (Cn\^-1) (tn\^-1)\] + Cntn/2 where Cn=last quantifiable concentration, tn=time at which Cn is measured, k=rate constant.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 11 of Cycle 1 | 39414.06 Hour square*ng per ml | Standard Deviation 51021.07 |
Primary
Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 1 of Cycle 1
AUMC is defined as the area under first moment plasma concentration-time curve from time of dosing up to definite time t, to infinity, or to the time of last measurable concentration determined by the following equation: AUMC(0 to infinity)=Cntn/k elimination(el) + Cn/k(el\^2) summation\[(tn - tn\^-1) (Cn\^-1) (tn\^-1)\] + Cntn/2 where Cn=last quantifiable concentration, tn=time at which Cn is measured, k=rate constant.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 1 of Cycle 1 | 20678.41 Hour square*ng per ml | Standard Deviation 54596.1 |
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 11 of Cycle 1
The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 11 of Cycle 1 | 349.62 Hour*ng per ml | Standard Deviation 178.81 |
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 1 of Cycle 1
The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration.
Time frame: Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 1 of Cycle 1 | 106.99 Hour*ng per ml | Standard Deviation 126.91 |
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 11 of Cycle 1
The AUC(0-t) is area under the plasma concentration-time curve from zero to the last quantifiable concentration determined by the trapezoidal rule.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 11 of Cycle 1 | 190.39 Hour*ng per mL | Standard Deviation 55.27 |
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 1 of Cycle 1
The AUC(0-t) is area under the plasma concentration-time curve from time zero to the last quantifiable concentration determined by the trapezoidal rule.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 1 of Cycle 1 | 51.86 Hour*ng per ml | Standard Deviation 30.56 |
Primary
Elimination Half-Life Period (T1/2) of Bortezomib on Day 11 of Cycle 1
The T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda\[z\]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Elimination Half-Life Period (T1/2) of Bortezomib on Day 11 of Cycle 1 | 51.55 Hours | Standard Deviation 87.2 |
Primary
Elimination Half-Life Period (T1/2) of Bortezomib on Day 1 of Cycle 1
The T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda\[z\]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Elimination Half-Life Period (T1/2) of Bortezomib on Day 1 of Cycle 1 | 0.08 Hours | Standard Deviation 0.07 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 11 of Cycle 1
The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 11 of Cycle 1 | 127.02 ng per ml | Standard Deviation 59.8 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 1 of Cycle 1
The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The Per-protocol (PP) population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 1 of Cycle 1 | 76.43 Nanogram per millileter (ng per ml) | Standard Deviation 38.47 |
Primary
Mean Residence Time (MRT) of Bortezomib in the Body on Day 11 of Cycle 1
The MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(infinity)/AUC(infinity) where AUMC(infinity) is area under the plasma concentration-time first moment curve from time zero to infinite time and AUC(infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Mean Residence Time (MRT) of Bortezomib in the Body on Day 11 of Cycle 1 | 88.74 Hour | Standard Deviation 58.38 |
Primary
Mean Residence Time (MRT) of Bortezomib in the Body on Day 1 of Cycle 1
The MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(infinity)/AUC(infinity) where AUMC(infinity) is area under the plasma concentration-time first moment curve from time zero to infinite time and AUC(infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Mean Residence Time (MRT) of Bortezomib in the Body on Day 1 of Cycle 1 | 65.97 Hour | Standard Deviation 121.65 |
Primary
Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline
The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.
Time frame: Baseline
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline | KPS Score = 80 | 3 Participants |
| Bortezomib | Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline | KPS Score = 90 | 7 Participants |
| Bortezomib | Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline | KPS Score = 100 | 2 Participants |
| Bortezomib | Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline | KPS Score = 70 | 2 Participants |
Primary
Number of Participants With KPS Score at Day 11 of Cycle 8
The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.
Time frame: Day 11 of Cycle 8
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With KPS Score at Day 11 of Cycle 8 | KPS Score = 50 | 2 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 11 of Cycle 8 | KPS Score = 60 | 4 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 11 of Cycle 8 | KPS Score = 70 | 1 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 11 of Cycle 8 | KPS Score = 80 | 3 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 11 of Cycle 8 | KPS Score = 90 | 2 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 11 of Cycle 8 | KPS Score = 100 | 2 Participants |
Primary
Number of Participants With KPS Score at Day 1 of Cycle 1
The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.
Time frame: Day 1 of Cycle 1
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 1 | KPS Score = 70 | 2 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 1 | KPS Score = 80 | 5 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 1 | KPS Score = 90 | 5 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 1 | KPS Score = 100 | 2 Participants |
Primary
Number of Participants With KPS Score at Day 1 of Cycle 3
The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.
Time frame: Day 1 of Cycle 3
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data. Here 'N' signifies those participants who were evaluated for this outcome measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 3 | KPS Score = 100 | 2 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 3 | KPS Score = 60 | 1 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 3 | KPS Score = 70 | 1 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 3 | KPS Score = 80 | 6 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 3 | KPS Score = 90 | 2 Participants |
Primary
Number of Participants With KPS Score at Day 1 of Cycle 5
The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.
Time frame: Day 1 of Cycle 5
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data. Here 'N' signifies those participants who were evaluated for this outcome measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 5 | KPS Score = 60 | 1 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 5 | KPS Score = 70 | 1 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 5 | KPS Score = 80 | 4 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 5 | KPS Score = 100 | 1 Participants |
Primary
Number of Participants With KPS Score at Day 1 of Cycle 7
The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.
Time frame: Day 1 of Cycle 7
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data. Here 'N' signifies those participants who were evaluated for this outcome measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 7 | KPS Score = 60 | 1 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 7 | KPS Score = 80 | 2 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 7 | KPS Score = 90 | 1 Participants |
| Bortezomib | Number of Participants With KPS Score at Day 1 of Cycle 7 | KPS Score = 100 | 1 Participants |
Primary
Number of Participants With Response to Treatment at Day 11 of Cycle 8
Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression.
Time frame: Day 11 of Cycle 8
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With Response to Treatment at Day 11 of Cycle 8 | Response | 2 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 11 of Cycle 8 | Partial response | 3 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 11 of Cycle 8 | Minimal response | 2 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 11 of Cycle 8 | Stable disease | 1 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 11 of Cycle 8 | Progression | 6 Participants |
Primary
Number of Participants With Response to Treatment at Day 1 of Cycle 5
Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression.
Time frame: Day 1 of Cycle 5
Population: The full analysis set (FAS) population included all the participants who received 1 dose of study medication and had post-dose efficacy data. Here 'N' signifies those participants who were evaluated for this outcome measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 5 | Progression | 1 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 5 | Complete response | 1 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 5 | Response | 2 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 5 | Partial Response | 2 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 5 | Stable disease | 1 Participants |
Primary
Number of Participants With Response to Treatment at Day 1 of Cycle 7
Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression.
Time frame: Day 1 of Cycle 7
Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data. Here 'N' signifies those participants who were evaluated for this outcome measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 7 | Stable disease | 1 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 7 | Response | 1 Participants |
| Bortezomib | Number of Participants With Response to Treatment at Day 1 of Cycle 7 | Partial Response | 3 Participants |
Primary
Systemic Clearance (CL) of Bortezomib on Day 11 of Cycle 1
Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-infinity).
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Systemic Clearance (CL) of Bortezomib on Day 11 of Cycle 1 | 4.68 Liter per Hour | Standard Deviation 2.46 |
Primary
Systemic Clearance (CL) of Bortezomib on Day 1 of Cycle 1
Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-infinity).
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Systemic Clearance (CL) of Bortezomib on Day 1 of Cycle 1 | 25.99 Liter per Hour | Standard Deviation 18.54 |
Primary
Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 11 of Cycle 1
Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 11 of Cycle 1 | 0.01 Per Hour | Standard Deviation 0.01 |
Primary
Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 1 of Cycle 1
Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 1 of Cycle 1 | 0.08 Per Hour | Standard Deviation 0.07 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 11 of Cycle 1
Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 11 of Cycle 1 | 0.08 Hours | Standard Deviation 0.01 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 1 of Cycle 1
Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 1 of Cycle 1 | 0.08 Hours | Standard Deviation 0 |
Primary
Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 11 of Cycle 1
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC\[0-infinity\])\*(AUMC\[0-infinity\])/AUC\[0-infinity\]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 11 of Cycle 1 | 331.68 Liter | Standard Deviation 85.81 |
Primary
Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 1 of Cycle 1
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC\[0-infinity\])\*(AUMC\[0-infinity\])/AUC\[0-infinity\]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
Time frame: 0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1
Population: The PP population included all the participants who received study medications as per the administration schedule and for whom blood samples were collected at all scheduled time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bortezomib | Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 1 of Cycle 1 | 483.71 Liter | Standard Deviation 403.04 |