A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Bortezomib, Velcade
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bortezomib
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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 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.
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01801436
First Posted
February 27, 2013
Last Updated
March 28, 2013
Sponsor
Johnson & Johnson Taiwan Ltd
1. Study Identification
Unique Protocol Identification Number
NCT01801436
Brief Title
A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma
Official Title
A Post Approval Commitment Study for Pharmacokinetic Analysis and Providing Expanded Access to Bortezomib (Velcade) for Patients With Multiple Myeloma Who Have Received at Least Two Previous Lines of Therapy and Are Refractory to or Have Relapsed After Their Last Therapy for Multiple Myeloma in Taiwan
Study Type
Interventional
2. Study Status
Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johnson & Johnson Taiwan Ltd
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Bortezomib, Velcade
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bortezomib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
VELCADE
Intervention Description
Bortezomib 1.3 mg per (m^2) on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles.
Primary Outcome Measure Information:
Title
Number of Participants With Response to Treatment at Day 1 of Cycle 5
Description
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
Title
Number of Participants With Response to Treatment at Day 1 of Cycle 7
Description
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
Title
Number of Participants With Response to Treatment at Day 11 of Cycle 8
Description
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
Title
Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline
Description
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
Title
Number of Participants With KPS Score at Day 1 of Cycle 1
Description
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
Title
Number of Participants With KPS Score at Day 1 of Cycle 3
Description
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
Title
Number of Participants With KPS Score at Day 1 of Cycle 5
Description
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
Title
Number of Participants With KPS Score at Day 1 of Cycle 7
Description
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
Title
Number of Participants With KPS Score at Day 11 of Cycle 8
Description
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
Title
Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 11 of Cycle 1
Description
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
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 11 of Cycle 1
Description
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
Title
Elimination Half-Life Period (T1/2) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Elimination Half-Life Period (T1/2) of Bortezomib on Day 11 of Cycle 1
Description
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
Title
Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 11 of Cycle 1
Description
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
Title
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
Description
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
Title
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
Description
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
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 11 of Cycle 1
Description
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
Title
Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 11 of Cycle 1
Description
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
Title
Mean Residence Time (MRT) of Bortezomib in the Body on Day 1 of Cycle 1
Description
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
Title
Mean Residence Time (MRT) of Bortezomib in the Body on Day 11 of Cycle 1
Description
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
Title
Systemic Clearance (CL) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Systemic Clearance (CL) of Bortezomib on Day 11 of Cycle 1
Description
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
Title
Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 1 of Cycle 1
Description
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
Title
Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 11 of Cycle 1
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Taiwan Ltd Clinical Trial
Organizational Affiliation
Johnson & Johnson Taiwan Ltd
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma
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