Trial Outcomes & Findings for Study of Buprenorphine HCl Buccal Film in the Treatment of Dental Pain (NCT NCT00941304)

NCT ID: NCT00941304

Last Updated: 2017-02-27

Results Overview

Time-weighted sum of pain intensity difference from baseline to 8 hours (SPID-8) where total score ranges from -80 (worst) to 80 (best) and a higher value indicates greater pain relief. Pain intensity was recorded using an 11-point numeric rating scale (NRS), where 0=none and 10=worst pain imaginable, in response to "What is your pain level at this time?"

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 153 participants
• Primary outcome timeframe: Baseline, 8 hours
• Results posted on: 2017-02-27

Participant Flow

Participant milestones

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 Buprenorphine hydrochloride (HCl) buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg Oxycodone 5-mg oral capsule and 2 placebo buccal films
Overall Study STARTED	31	30	31	30	31
Overall Study COMPLETED	30	30	31	30	31
Overall Study NOT COMPLETED	1	0	0	0	0

Reasons for withdrawal

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 Buprenorphine hydrochloride (HCl) buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg Oxycodone 5-mg oral capsule and 2 placebo buccal films
Overall Study Lost to Follow-up	1	0	0	0	0

Baseline Characteristics

Study of Buprenorphine HCl Buccal Film in the Treatment of Dental Pain

Baseline characteristics by cohort

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films	Total n=153 Participants Total of all reporting groups
Age, Continuous	21.0 years n=5 Participants	21.0 years n=7 Participants	21.0 years n=5 Participants	22.0 years n=4 Participants	21.0 years n=21 Participants	21.0 years n=10 Participants
Gender Female	22 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	18 Participants n=4 Participants	16 Participants n=21 Participants	96 Participants n=10 Participants
Gender Male	9 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	15 Participants n=21 Participants	57 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline, 8 hours

Population: Analysis based on intent-to-treat (ITT) population; all subjects who received study drug and provided at least 1 post-dose assessment.

Time-weighted sum of pain intensity difference from baseline to 8 hours (SPID-8) where total score ranges from -80 (worst) to 80 (best) and a higher value indicates greater pain relief. Pain intensity was recorded using an 11-point numeric rating scale (NRS), where 0=none and 10=worst pain imaginable, in response to "What is your pain level at this time?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Sum of Pain Intensity Difference From Baseline to 8 Hours	6.016 units on a scale Standard Deviation 19.9786	11.867 units on a scale Standard Deviation 20.7418	11.282 units on a scale Standard Deviation 22.9711	5.283 units on a scale Standard Deviation 17.6360	4.290 units on a scale Standard Deviation 14.8645

SECONDARY outcome

Timeframe: 8 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Time-weighted sum of total pain relief over 8 hours (TOPAR-8) where total score ranges from 0 (worst) to 32 (best) and higher values indicate greater pain relief. Pain relief (PAR) was recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to "How much relief have you had from your starting pain?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Total Pain Relief Over 8 Hours	7.274 units on a scale Standard Deviation 8.7136	9.858 units on a scale Standard Deviation 9.3550	10.500 units on a scale Standard Deviation 9.9358	6.392 units on a scale Standard Deviation 8.6235	6.242 units on a scale Standard Deviation 6.6813

SECONDARY outcome

Timeframe: 8 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Time-weighted sum of PAR and pain intensity difference (PID) over 8 hours (SPRID-8) where total score ranges from -80 (worst) to 112 (best) and higher values indicate greater pain relief. PAR was recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to "How much relief have you had from your starting pain?" PID determined as the change from baseline pain intensity assessment. Pain intensity was recorded using an 11-point NRS, where 0=none and 10=worst pain imaginable, in response to "What is your pain level at this time?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Sum of Pain Relief and Intensity Differences Over 8 Hours	13.290 units on a scale Standard Deviation 28.1677	21.725 units on a scale Standard Deviation 29.7031	21.782 units on a scale Standard Deviation 32.2047	11.675 units on a scale Standard Deviation 25.8038	10.532 units on a scale Standard Deviation 20.5848

SECONDARY outcome

Timeframe: 2 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Time-weighted sum of PAR and PID over 2 hours (SPRID-2) where total score ranges from 0 (worst) to 8 (best) and higher values indicate greater pain relief. PAR was recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to "How much relief have you had from your starting pain?" PID determined as the change from baseline pain intensity assessment. Pain intensity was recorded using an 11-point NRS, where 0=none and 10=worst pain imaginable, in response to "What is your pain level at this time?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Sum of Pain Relief and Intensity Differences Over 2 Hours	0.339 units on a scale Standard Deviation 3.4896	1.533 units on a scale Standard Deviation 3.5718	1.056 units on a scale Standard Deviation 3.9769	0.850 units on a scale Standard Deviation 3.5505	1.484 units on a scale Standard Deviation 3.6009

SECONDARY outcome

Timeframe: 24 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

The maximum PID at any time following dosing determined from the change from baseline pain intensity assessment. Pain intensity was recorded using an 11-point NRS, where 0=none and 10=worst pain imaginable, in response to "What is your pain level at this time?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Peak Pain Intensity Difference	2.2 units on a scale Standard Deviation 3.50	2.9 units on a scale Standard Deviation 3.30	2.8 units on a scale Standard Deviation 3.35	1.5 units on a scale Standard Deviation 2.50	1.9 units on a scale Standard Deviation 2.61

SECONDARY outcome

Timeframe: 24 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Maximum pain relief (PAR) at any time following dosing, recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to "How much relief have you had from your starting pain?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Peak Pain Relief	1.5 units on a scale Standard Deviation 1.59	1.8 units on a scale Standard Deviation 1.61	1.9 units on a scale Standard Deviation 1.51	1.1 units on a scale Standard Deviation 1.36	1.3 units on a scale Standard Deviation 1.33

SECONDARY outcome

Timeframe: 8 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Time to onset of analgesia defined as median time to perceptible pain relief if confirmed by experiencing meaningful pain relief from time of study drug administration.

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Onset of Analgesia	NA hours Interval 3.083 to Median time to onset of analgesia and/or corresponding 95% confidence interval (CI) could not be determined as more than 50% of the subjects in treatment group failed to activate the stopwatch times within the protocol-specified 8-hour window.	2.43 hours Interval 0.617 to Median time to onset of analgesia and/or corresponding 95% confidence interval (CI) could not be determined as more than 50% of the subjects in treatment group failed to activate the stopwatch times within the protocol-specified 8-hour window.	NA hours Interval 0.75 to Median time to onset of analgesia and/or corresponding 95% confidence interval (CI) could not be determined as more than 50% of the subjects in treatment group failed to activate the stopwatch times within the protocol-specified 8-hour window.	NA hours Median time to onset of analgesia and/or corresponding 95% confidence interval (CI) could not be determined as more than 50% of the subjects in treatment group failed to activate the stopwatch times within the protocol-specified 8-hour window.	NA hours Interval 1.017 to Median time to onset of analgesia and/or corresponding 95% confidence interval (CI) could not be determined as more than 50% of the subjects in treatment group failed to activate the stopwatch times within the protocol-specified 8-hour window.

SECONDARY outcome

Timeframe: 24 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Duration of analgesia was the median time to use of rescue medication; earliest concomitant medication start time for medications identified as rescue medications from time of study drug administration.

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Duration of Analgesia	1.75 hours Interval 1.667 to 5.083	2.62 hours Interval 1.783 to 19.117	4.12 hours Interval 2.067 to Corresponding 95% CI for duration of analgesia could not be determined as many subjects did not use rescue medication within 24 hours.	1.69 hours Interval 1.583 to 3.3	2.17 hours Interval 1.683 to 2.75

SECONDARY outcome

Timeframe: 8 hours and 24 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Subjects rated the global effectiveness of study drug as poor, fair, good, or excellent, in response to "Overall, how would you rate the study medication you received for pain?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Percentage of Participants Reporting a Global Rating of Study Drug as "Excellent" Excellent at 8 hours	3.2 percentage of participants	6.7 percentage of participants	9.7 percentage of participants	6.7 percentage of participants	3.2 percentage of participants
Percentage of Participants Reporting a Global Rating of Study Drug as "Excellent" Excellent at 24 hours	9.7 percentage of participants	13.3 percentage of participants	12.9 percentage of participants	3.3 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 24 hours

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Investigators rated the global effectiveness of study drug as poor, fair, good, or excellent, in response to "Overall, how would you rate the study medication for this subject?"

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Percentage of Participants With "Excellent" Investigator Global Rating of Study Drug	6.5 percentage of participants	13.3 percentage of participants	12.9 percentage of participants	3.3 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (screening), 2 hours 15 minutes postdose

Population: Analysis based on ITT population; all subjects who received study drug and provided at least 1 post-dose assessment.

Cognition assessed using computer-based CNS Vital Signs® neurocognitive function test (CNS-VS), including symbol digit coding, Stroop test, and shifting attention test to measure cognitive flexibility, executive functioning, processing speed, and reaction time(*). Scores are computed from raw score calculations using the data values of individual subtests. An asterisk denotes that "lower score is better", otherwise higher scores are better.

Outcome measures

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 Participants Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 Participants Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 Participants Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=30 Participants Oxycodone 5-mg oral capsule and 2 placebo buccal films
Change From Baseline in Cognitive Assessment Using CNS-VS Cognitive flexibility	5.9 Score Standard Deviation 17.14	4.0 Score Standard Deviation 18.93	-3.2 Score Standard Deviation 14.53	7.3 Score Standard Deviation 10.81	2.1 Score Standard Deviation 17.56
Change From Baseline in Cognitive Assessment Using CNS-VS Executive functioning	5.7 Score Standard Deviation 17.35	4.1 Score Standard Deviation 16.00	-3.0 Score Standard Deviation 13.49	7.2 Score Standard Deviation 10.83	2.2 Score Standard Deviation 17.19
Change From Baseline in Cognitive Assessment Using CNS-VS Processing speed	-0.8 Score Standard Deviation 7.64	0.8 Score Standard Deviation 6.73	-9.1 Score Standard Deviation 14.48	2.8 Score Standard Deviation 9.12	1.5 Score Standard Deviation 9.63
Change From Baseline in Cognitive Assessment Using CNS-VS Reaction time	26.9 Score Standard Deviation 79.82	-19.5 Score Standard Deviation 102.16	29.7 Score Standard Deviation 157.55	-3.5 Score Standard Deviation 56.09	-8.9 Score Standard Deviation 61.13

Adverse Events

0.25-mg Buprenorphine HCl Buccal Film, M2

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

0.5-mg Buprenorphine HCl Buccal Film, M2

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

0.5-mg Buprenorphine HCl Buccal Film, M1

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Oxycodone 5 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	0.25-mg Buprenorphine HCl Buccal Film, M2 n=31 participants at risk Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M2 n=30 participants at risk Buprenorphine HCl buccal film 0.5-mg modified formulation 2, placebo buccal film, and placebo oral capsule	0.5-mg Buprenorphine HCl Buccal Film, M1 n=31 participants at risk Buprenorphine HCl buccal film 0.5-mg modified formulation 1, placebo buccal film, and placebo oral capsule	Placebo n=30 participants at risk Placebo oral capsule and 2 placebo buccal films	Oxycodone 5 mg n=31 participants at risk Oxycodone 5-mg oral capsule and 2 placebo buccal films
Gastrointestinal disorders Nausea	19.4% 6/31 • Number of events 6 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	46.7% 14/30 • Number of events 14 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	64.5% 20/31 • Number of events 20 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/30 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	6.5% 2/31 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug
Gastrointestinal disorders Vomiting	6.5% 2/31 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	40.0% 12/30 • Number of events 12 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	51.6% 16/31 • Number of events 16 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/30 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/31 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug
Infections and infestations Alveolar osteitis	0.00% 0/31 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	6.7% 2/30 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	9.7% 3/31 • Number of events 3 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	6.7% 2/30 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	6.5% 2/31 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug
Nervous system disorders Dizziness	16.1% 5/31 • Number of events 5 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	20.0% 6/30 • Number of events 7 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	41.9% 13/31 • Number of events 13 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	3.3% 1/30 • Number of events 1 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/31 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug
Nervous system disorders Headache	6.5% 2/31 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	13.3% 4/30 • Number of events 4 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	6.5% 2/31 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/30 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	6.5% 2/31 • Number of events 2 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/31 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/30 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	9.7% 3/31 • Number of events 3 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/30 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug	0.00% 0/31 • From study drug administration (day 1) to follow-up visit (day 6 to 10) Analysis based on Safety population; all subjects who received any study drug

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals Inc.

Email: clinicalsite.inquiries@endo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER