Trial Outcomes & Findings for Safety and Pharmacokinetics Study of Redosing EXPAREL in Healthy Volunteers (NCT NCT02210247)
NCT ID: NCT02210247
Last Updated: 2021-07-06
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
60 participants
Primary outcome timeframe
Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects
Results posted on
2021-07-06
Participant Flow
Participant milestones
| Measure |
Cohort 1
Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.
EXPAREL
|
Cohort 2
Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
12
|
12
|
12
|
|
Overall Study
COMPLETED
|
12
|
12
|
12
|
12
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Pharmacokinetics Study of Redosing EXPAREL in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Cohort 1
n=12 Participants
Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.
EXPAREL
|
Cohort 2
n=12 Participants
Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
n=12 Participants
Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
n=12 Participants
Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
n=12 Participants
Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
45.6 years
STANDARD_DEVIATION 11.90 • n=5 Participants
|
37.8 years
STANDARD_DEVIATION 11.66 • n=7 Participants
|
36.9 years
STANDARD_DEVIATION 10.83 • n=5 Participants
|
41.6 years
STANDARD_DEVIATION 12.38 • n=4 Participants
|
44.1 years
STANDARD_DEVIATION 14.56 • n=21 Participants
|
41.2 years
STANDARD_DEVIATION 12.39 • n=10 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
23 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
37 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
60 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
42 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
18 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
12 participants
n=5 Participants
|
12 participants
n=4 Participants
|
12 participants
n=21 Participants
|
60 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjectsOutcome measures
| Measure |
Cohort 1
n=12 Participants
Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.
EXPAREL
|
Cohort 2
n=12 Participants
Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
n=12 Participants
Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
n=12 Participants
Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
n=12 Participants
Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
129 ng/mL
Standard Deviation 47
|
207 ng/mL
Standard Deviation 57
|
202 ng/mL
Standard Deviation 74
|
290 ng/mL
Standard Deviation 119
|
246 ng/mL
Standard Deviation 78
|
PRIMARY outcome
Timeframe: Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjectsOutcome measures
| Measure |
Cohort 1
n=12 Participants
Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.
EXPAREL
|
Cohort 2
n=12 Participants
Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
n=12 Participants
Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
n=12 Participants
Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
n=12 Participants
Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
|---|---|---|---|---|---|
|
Time to Maximum Concentration (Tmax)
|
24 hours
Interval 24.0 to 72.0
|
48 hours
Interval 24.0 to 72.0
|
48 hours
Interval 1.0 to 72.0
|
36 hours
Interval 24.0 to 72.0
|
24 hours
Interval 8.0 to 72.0
|
PRIMARY outcome
Timeframe: Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjectsOutcome measures
| Measure |
Cohort 1
n=12 Participants
Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.
EXPAREL
|
Cohort 2
n=12 Participants
Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
n=12 Participants
Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
n=12 Participants
Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
n=12 Participants
Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC(0-last)]
|
5917 H*ng/mL
Standard Deviation 1738
|
10976 H*ng/mL
Standard Deviation 2879
|
10201 H*ng/mL
Standard Deviation 3721
|
15227 H*ng/mL
Standard Deviation 7463
|
11567 H*ng/mL
Standard Deviation 3737
|
PRIMARY outcome
Timeframe: Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjectsPopulation: Where n per group \<12, values were either not calculated or not reported.
Outcome measures
| Measure |
Cohort 1
n=2 Participants
Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.
EXPAREL
|
Cohort 2
n=6 Participants
Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
n=6 Participants
Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
n=2 Participants
Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
n=7 Participants
Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
|---|---|---|---|---|---|
|
Apparent Terminal Elimination Half-life
|
80.24 hours
Standard Deviation 22.64
|
44.88 hours
Standard Deviation 25.64
|
51.70 hours
Standard Deviation 26.99
|
33.22 hours
Standard Deviation 3.80
|
59.13 hours
Standard Deviation 25.03
|
PRIMARY outcome
Timeframe: Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjectsPopulation: Where n per group \<12, values were either not calculated or not reported.
Outcome measures
| Measure |
Cohort 1
n=2 Participants
Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.
EXPAREL
|
Cohort 2
n=6 Participants
Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
n=6 Participants
Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
n=2 Participants
Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
n=7 Participants
Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
|---|---|---|---|---|---|
|
The Apparent Terminal Elimination Rate Constant (λz)
|
0.009 1/hours
Standard Deviation 0.003
|
0.019 1/hours
Standard Deviation 0.007
|
0.016 1/hours
Standard Deviation 0.007
|
0.021 1/hours
Standard Deviation 0.002
|
0.014 1/hours
Standard Deviation 0.006
|
Adverse Events
Cohort 1
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort 2
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 3
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Cohort 4
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 5
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 |
Cohort 1
n=12 participants at risk
Cohort 1 received a single dose of EXPAREL 266 mg on Day 1. No additional dose was given.
EXPAREL
|
Cohort 2
n=12 participants at risk
Cohort 2 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours.
EXPAREL
|
Cohort 3
n=12 participants at risk
Cohort 3 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours.
EXPAREL
|
Cohort 4
n=12 participants at risk
Cohort 4 received a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours.
EXPAREL
|
Cohort 5
n=12 participants at risk
Cohort 5 received a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL).
EXPAREL
|
|---|---|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
|
General disorders
Injection-site reaction
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
2/12 • Number of events 2
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
General disorders
Vessel puncture site haematoma
|
16.7%
2/12 • Number of events 2
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Nervous system disorders
Headache
|
25.0%
3/12 • Number of events 3
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Nervous system disorders
Presyncope
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
Additional Information
Pacira Medical Information
Pacira Pharmaceuticals Inc.
Phone: 1-855-793-9727
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place