Trial Outcomes & Findings for A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma (NCT NCT01801436)
NCT ID: NCT01801436
Last Updated: 2013-05-16
Results Overview
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.
COMPLETED
PHASE3
14 participants
Day 1 of Cycle 5
2013-05-16
Participant Flow
Participant milestones
| Measure |
Bortezomib
Participants received 1.3 milligram per meter square (mg per m\^2) of bortezomib on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles.
|
|---|---|
|
Overall Study
STARTED
|
14
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
Bortezomib
Participants received 1.3 milligram per meter square (mg per m\^2) of bortezomib on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Progressive disease
|
4
|
Baseline Characteristics
A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Bortezomib
n=14 Participants
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.
|
|---|---|
|
Age Continuous
|
62.63 Years
STANDARD_DEVIATION 8.31 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 5Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=7 Participants
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.
|
|---|---|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 5
Complete response
|
1 Participants
|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 5
Response
|
2 Participants
|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 5
Partial Response
|
2 Participants
|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 5
Stable disease
|
1 Participants
|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 5
Progression
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 7Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=5 Participants
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.
|
|---|---|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 7
Response
|
1 Participants
|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 7
Partial Response
|
3 Participants
|
|
Number of Participants With Response to Treatment at Day 1 of Cycle 7
Stable disease
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 11 of Cycle 8Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
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.
Outcome measures
| Measure |
Bortezomib
n=14 Participants
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.
|
|---|---|
|
Number of Participants With Response to Treatment at Day 11 of Cycle 8
Response
|
2 Participants
|
|
Number of Participants With Response to Treatment at Day 11 of Cycle 8
Partial response
|
3 Participants
|
|
Number of Participants With Response to Treatment at Day 11 of Cycle 8
Minimal response
|
2 Participants
|
|
Number of Participants With Response to Treatment at Day 11 of Cycle 8
Stable disease
|
1 Participants
|
|
Number of Participants With Response to Treatment at Day 11 of Cycle 8
Progression
|
6 Participants
|
PRIMARY outcome
Timeframe: BaselinePopulation: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
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.
Outcome measures
| Measure |
Bortezomib
n=14 Participants
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.
|
|---|---|
|
Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline
KPS Score = 70
|
2 Participants
|
|
Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline
KPS Score = 80
|
3 Participants
|
|
Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline
KPS Score = 90
|
7 Participants
|
|
Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline
KPS Score = 100
|
2 Participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 1Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
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.
Outcome measures
| Measure |
Bortezomib
n=14 Participants
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.
|
|---|---|
|
Number of Participants With KPS Score at Day 1 of Cycle 1
KPS Score = 70
|
2 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 1
KPS Score = 80
|
5 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 1
KPS Score = 90
|
5 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 1
KPS Score = 100
|
2 Participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 3Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=12 Participants
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.
|
|---|---|
|
Number of Participants With KPS Score at Day 1 of Cycle 3
KPS Score = 60
|
1 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 3
KPS Score = 70
|
1 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 3
KPS Score = 80
|
6 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 3
KPS Score = 90
|
2 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 3
KPS Score = 100
|
2 Participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 5Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=7 Participants
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.
|
|---|---|
|
Number of Participants With KPS Score at Day 1 of Cycle 5
KPS Score = 60
|
1 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 5
KPS Score = 70
|
1 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 5
KPS Score = 80
|
4 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 5
KPS Score = 100
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 7Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=5 Participants
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.
|
|---|---|
|
Number of Participants With KPS Score at Day 1 of Cycle 7
KPS Score = 60
|
1 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 7
KPS Score = 80
|
2 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 7
KPS Score = 90
|
1 Participants
|
|
Number of Participants With KPS Score at Day 1 of Cycle 7
KPS Score = 100
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 11 of Cycle 8Population: The FAS population included all the participants who received 1 dose of study medication and had post-dose efficacy data.
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.
Outcome measures
| Measure |
Bortezomib
n=14 Participants
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.
|
|---|---|
|
Number of Participants With KPS Score at Day 11 of Cycle 8
KPS Score = 50
|
2 Participants
|
|
Number of Participants With KPS Score at Day 11 of Cycle 8
KPS Score = 60
|
4 Participants
|
|
Number of Participants With KPS Score at Day 11 of Cycle 8
KPS Score = 70
|
1 Participants
|
|
Number of Participants With KPS Score at Day 11 of Cycle 8
KPS Score = 80
|
3 Participants
|
|
Number of Participants With KPS Score at Day 11 of Cycle 8
KPS Score = 90
|
2 Participants
|
|
Number of Participants With KPS Score at Day 11 of Cycle 8
KPS Score = 100
|
2 Participants
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
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 outcome
Timeframe: 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 1Population: 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.
The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 11 of Cycle 1
|
127.02 ng per ml
Standard Deviation 59.80
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 1 of Cycle 1
|
0.08 Hours
Standard Deviation 0.00
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 11 of Cycle 1
|
0.08 Hours
Standard Deviation 0.01
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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).
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Elimination Half-Life Period (T1/2) of Bortezomib on Day 1 of Cycle 1
|
0.08 Hours
Standard Deviation 0.07
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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).
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Elimination Half-Life Period (T1/2) of Bortezomib on Day 11 of Cycle 1
|
51.55 Hours
Standard Deviation 87.20
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 1 of Cycle 1
|
0.08 Per Hour
Standard Deviation 0.07
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 11 of Cycle 1
|
0.01 Per Hour
Standard Deviation 0.01
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
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 outcome
Timeframe: 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 1Population: 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.
The AUC(0-t) is area under the plasma concentration-time curve from zero to the last quantifiable concentration determined by the trapezoidal rule.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
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 outcome
Timeframe: Day 1 of Cycle 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
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 outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
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 outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
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 outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
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 outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Mean Residence Time (MRT) of Bortezomib in the Body on Day 1 of Cycle 1
|
65.97 Hour
Standard Deviation 121.65
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Mean Residence Time (MRT) of Bortezomib in the Body on Day 11 of Cycle 1
|
88.74 Hour
Standard Deviation 58.38
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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).
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Systemic Clearance (CL) of Bortezomib on Day 1 of Cycle 1
|
25.99 Liter per Hour
Standard Deviation 18.54
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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).
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Systemic Clearance (CL) of Bortezomib on Day 11 of Cycle 1
|
4.68 Liter per Hour
Standard Deviation 2.46
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 1 of Cycle 1
|
483.71 Liter
Standard Deviation 403.04
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Bortezomib
n=10 Participants
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.
|
|---|---|
|
Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 11 of Cycle 1
|
331.68 Liter
Standard Deviation 85.81
|
Adverse Events
Bortezomib
Serious adverse events
| Measure |
Bortezomib
n=14 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Pancytopenia
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Gastritis
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Mouth ulceration
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Nausea
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Pneumonia
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Sepsis
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Urinary tract infection
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Ammonia abnormal
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood albumin decreased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood antidiuretic hormone abnormal
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood calcium increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood glucose decreased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood potassium decreased
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood sodium increased
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Mini mental status examination abnormal
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Platelet count decreased
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Haemorrhage intracranial
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Syncope
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Psychiatric disorders
Confusional state
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Fatigue
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Vascular disorders
Hypotension
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
Other adverse events
| Measure |
Bortezomib
n=14 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Tachycardia
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Abdominal distension
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Abdominal pain upper
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Colitis
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Constipation
|
50.0%
7/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Diarrhoea
|
57.1%
8/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Dyspepsia
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Gingival ulceration
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Ileus
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Nausea
|
35.7%
5/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Chest pain
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Irritability
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Localised oedema
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Nodule
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Oedema
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Oedema peripheral
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Pain
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Pyrexia
|
50.0%
7/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Device related infection
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Herpes simplex
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Herpes zoster
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Infections - pathogen unspecified
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Oral candidiasis
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Salmonella bacteraemia
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Upper respiratory tract infection
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Infections and infestations
Urinary tract infection
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Injury, poisoning and procedural complications
Excoriation
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Injury, poisoning and procedural complications
Fracture
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Alanine aminotransferase increased
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
7/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood albumin decreased
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood alkaline phosphatase increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood amylase increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood calcium decreased
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood calcium increased
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood cholesterol increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood creatinine abnormal
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood creatinine increased
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood glucose increased
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood lactate dehydrogenase increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood magnesium decreased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood magnesium increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood phosphorus decreased
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood potassium decreased
|
35.7%
5/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood sodium increased
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood triglycerides increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood uric acid increased
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Gamma-glutamyltransferase increased
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Haemoglobin decreased
|
64.3%
9/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Neutrophil count decreased
|
78.6%
11/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Platelet count decreased
|
71.4%
10/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Weight decreased
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
White blood cell count decreased
|
78.6%
11/14 • Basleine up to Day 11 of Cycle 8
|
|
Metabolism and nutrition disorders
Anorexia
|
42.9%
6/14 • Basleine up to Day 11 of Cycle 8
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
35.7%
5/14 • Basleine up to Day 11 of Cycle 8
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Dizziness
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Headache
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Hypoaesthesia
|
42.9%
6/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Nervous system disorder
|
35.7%
5/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Neuralgia
|
50.0%
7/14 • Basleine up to Day 11 of Cycle 8
|
|
Nervous system disorders
Tremor
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Psychiatric disorders
Anxiety
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Psychiatric disorders
Confusional state
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Psychiatric disorders
Depression
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Psychiatric disorders
Insomnia
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Renal and urinary disorders
Dysuria
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Renal and urinary disorders
Renal failure
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
35.7%
5/14 • Basleine up to Day 11 of Cycle 8
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
28.6%
4/14 • Basleine up to Day 11 of Cycle 8
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.3%
2/14 • Basleine up to Day 11 of Cycle 8
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
Vascular disorders
Hypertension
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Vascular disorders
Hypotension
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
1/14 • Basleine up to Day 11 of Cycle 8
|
|
General disorders
Fatigue
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
|
Investigations
Blood potassium increased
|
21.4%
3/14 • Basleine up to Day 11 of Cycle 8
|
Additional Information
Medical Affairs Director
Janssen Pharmaceutical Taiwan
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60