Trial Outcomes & Findings for Study to Evaluate Daptomycin Given During Dialysis and After Dialysis (NCT NCT00882557)
NCT ID: NCT00882557
Last Updated: 2018-02-06
Results Overview
Area under the plasma concentration versus time curve from time 0 to infinity for daptomycin doses
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Within 30 minutes prior to the start of the infusion, mid-infusion, and end of the infusion; at 1, 2, 4, 6, 9, 24, and 48 hours after the end of the infusion; and just prior to the next hemodialysis session (i.e., 68 hours post-infusion)
Results posted on
2018-02-06
Participant Flow
Subjects evaluated for entry within 7 days prior to randomization, washout period of 7-14 days between doses, subjects began Day 1 on Friday of Monday/Wednesday/Friday or Saturday of Tuesday/Thursday/Saturday hemodialysis schedule
Participant milestones
| Measure |
Sequence BA
All subjects received 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B) and 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A).
|
Sequence AB
All subjects received 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A) and 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B).
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
Completed Dose 1
|
8
|
7
|
|
Overall Study
Completed Dose 2
|
6
|
7
|
|
Overall Study
COMPLETED
|
6
|
7
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Sequence BA
All subjects received 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B) and 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A).
|
Sequence AB
All subjects received 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A) and 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B).
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Trouble with Vein Access
|
1
|
0
|
|
Overall Study
Randomized Not Treated
|
0
|
1
|
Baseline Characteristics
Study to Evaluate Daptomycin Given During Dialysis and After Dialysis
Baseline characteristics by cohort
| Measure |
Sequence BA
n=8 Participants
All subjects received 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B) and 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A).
|
Sequence AB
n=7 Participants
All subjects received 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A) and 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B).
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.6 years
STANDARD_DEVIATION 13.19 • n=99 Participants
|
55.3 years
STANDARD_DEVIATION 6.05 • n=107 Participants
|
53.3 years
STANDARD_DEVIATION 10.31 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion, mid-infusion, and end of the infusion; at 1, 2, 4, 6, 9, 24, and 48 hours after the end of the infusion; and just prior to the next hemodialysis session (i.e., 68 hours post-infusion)Population: The primary endpoints are measured on the PK population, defined as all subjects who received both the 6 mg/kg dose and 9 mg/kg dose
Area under the plasma concentration versus time curve from time 0 to infinity for daptomycin doses
Outcome measures
| Measure |
6 mg/kg After Hemodialysis (Regimen B)
n=13 Participants
Daptomycin (6 mg/kg IV) after hemodialysis using high-flux membranes
|
9 mg/kg During Hemodialysis (Regimen A)
n=13 Participants
Daptomycin (9 mg/kg IV) during the last 30 minutes of hemodialysis using high-flux membrane
|
|---|---|---|
|
Evaluation of Area Under the Curve From Time 0 to Infinity
|
1692 hr*ug/mL
Interval 962.0 to 2524.0
|
2708 hr*ug/mL
Interval 1719.0 to 4010.0
|
SECONDARY outcome
Timeframe: Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).Population: Safety population, defined as all subjects who received at least one dose of daptomycin
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
Outcome measures
| Measure |
6 mg/kg After Hemodialysis (Regimen B)
n=15 Participants
Daptomycin (6 mg/kg IV) after hemodialysis using high-flux membranes
|
9 mg/kg During Hemodialysis (Regimen A)
n=13 Participants
Daptomycin (9 mg/kg IV) during the last 30 minutes of hemodialysis using high-flux membrane
|
|---|---|---|
|
Treatment-emergent Adverse Events
|
2 participants
|
3 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Within 30 minutes prior to the start of the infusion, mid-infusion, and end of the infusion; at 1, 2, 4, 6, 9, 24, and 48 hours after the end of the infusion; and just prior to the next hemodialysis session (i.e., 68 hours post-infusion)Population: PK Population - defined as all subjects who received both doses of daptomycin
Maximum plasma concentration over the entire sampling phase directly obtained from the experimental plasma concentration time data, without interpolation.
Outcome measures
| Measure |
6 mg/kg After Hemodialysis (Regimen B)
n=13 Participants
Daptomycin (6 mg/kg IV) after hemodialysis using high-flux membranes
|
9 mg/kg During Hemodialysis (Regimen A)
n=13 Participants
Daptomycin (9 mg/kg IV) during the last 30 minutes of hemodialysis using high-flux membrane
|
|---|---|---|
|
Maximum Plasma Concentration
|
70.5 ug/mL
Interval 35.8 to 104.0
|
100 ug/mL
Interval 56.5 to 211.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 68 hours post doseSampling time at which maximum plasma concentration occurred, obtained directly from the experimental plasma concentration time data, without interpolation.
Outcome measures
| Measure |
6 mg/kg After Hemodialysis (Regimen B)
n=13 Participants
Daptomycin (6 mg/kg IV) after hemodialysis using high-flux membranes
|
9 mg/kg During Hemodialysis (Regimen A)
n=13 Participants
Daptomycin (9 mg/kg IV) during the last 30 minutes of hemodialysis using high-flux membrane
|
|---|---|---|
|
Time to Maximum Concentration
|
0.50 Hours
Interval 0.5 to 1.0
|
0.50 Hours
Interval 0.5 to 0.65
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 68 hours post doseApparent terminal half-life.
Outcome measures
| Measure |
6 mg/kg After Hemodialysis (Regimen B)
n=13 Participants
Daptomycin (6 mg/kg IV) after hemodialysis using high-flux membranes
|
9 mg/kg During Hemodialysis (Regimen A)
n=13 Participants
Daptomycin (9 mg/kg IV) during the last 30 minutes of hemodialysis using high-flux membrane
|
|---|---|---|
|
Half-life
|
29.8 Hours
Interval 19.7 to 38.1
|
31.1 Hours
Interval 21.9 to 45.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 68 hours post dosePopulation: PK Population - defined as all subjects who received both doses of daptomycin
Plasma clearance is dose (µg) divided by area under the concentration versus time curve from time 0 to last quantifiable concentration time.
Outcome measures
| Measure |
6 mg/kg After Hemodialysis (Regimen B)
n=13 Participants
Daptomycin (6 mg/kg IV) after hemodialysis using high-flux membranes
|
9 mg/kg During Hemodialysis (Regimen A)
n=13 Participants
Daptomycin (9 mg/kg IV) during the last 30 minutes of hemodialysis using high-flux membrane
|
|---|---|---|
|
Clearance of Daptomycin
|
3.54 mL/hr/kg
Interval 2.38 to 6.23
|
3.32 mL/hr/kg
Interval 2.24 to 5.23
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 68 hours post doseVolume of distribution at steady state (mL) calculated as the product of clearance and mean residence time.
Outcome measures
| Measure |
6 mg/kg After Hemodialysis (Regimen B)
n=13 Participants
Daptomycin (6 mg/kg IV) after hemodialysis using high-flux membranes
|
9 mg/kg During Hemodialysis (Regimen A)
n=13 Participants
Daptomycin (9 mg/kg IV) during the last 30 minutes of hemodialysis using high-flux membrane
|
|---|---|---|
|
Volume of Distribution
|
137 mL/kg
Interval 107.0 to 221.0
|
145 mL/kg
Interval 115.0 to 219.0
|
Adverse Events
Sequence BA
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Sequence AB
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sequence BA
n=8 participants at risk
All subjects received 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B) and 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A).
|
Sequence AB
n=7 participants at risk
All subjects received 1 dose of daptomycin 9 mg/kg during the last 30 minutes of hemodialysis (Regimen A) and 1 dose of daptomycin 6 mg/kg after hemodialysis (Regimen B).
|
|---|---|---|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/8 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
14.3%
1/7 • Number of events 1 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
14.3%
1/7 • Number of events 2 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
|
Vascular disorders
Hypotension
|
12.5%
1/8 • Number of events 1 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
14.3%
1/7 • Number of events 1 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/8 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
14.3%
1/7 • Number of events 1 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
|
General disorders
Pyrexia
|
0.00%
0/8 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
14.3%
1/7 • Number of events 1 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
|
Musculoskeletal and connective tissue disorders
Temporomandibular joint syndrome
|
0.00%
0/8 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
14.3%
1/7 • Number of events 1 • Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15).
Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.
|
Additional Information
Ed Campanaro/Vice President, Clinical Operations
Cubist Pharmaceuticals, Inc.
Phone: 781-860-8318
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The first publication is initiated by Cubist. If First Publication not published within 1 year of Study conclusion or termination, Investigator has right to publish and disclose the Data. Prior to any submission for publication, presentation, or communication of results or information arising from the Study, Investigator shall provide Cubist at least 90 days for review and comment upon the manuscript or other material for such publication or presentation.
- Publication restrictions are in place
Restriction type: OTHER