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

A Double-Blind, Double-Dummy, Placebo- and Active Controlled Evaluation of the Efficacy, Safety and Tolerability of Buprenorphine HCl Buccal Film in the Treatment of Pain Associated With Third Molar Extraction

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00941304

Enrollment

153

Registered

2009-07-17

Start date

2009-08-31

Completion date

2009-11-30

Last updated

2017-02-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dental Pain

Brief summary

The purpose of this study is to assess the activity of buprenorphine hydrochloride (HCl) buccal film in the treatment of dental pain.

Interventions

DRUGOxycodone

Single-dose of over-encapsulated oral 5-mg oxycodone capsule

DRUGBuprenorphine

Single-dose of buprenorphine HCl buccal film

DRUGPlacebo Film

Single-dose of placebo buccal film

DRUGPlacebo Capsule

Single-dose of oral placebo capsule

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Inclusion criteria

* extraction of 2 or more third molars, at least 1 of which must be fully or partially impacted in mandibular bone * males or non-pregnant females, aged 18 to 45 years * good general health and capable of providing informed consent

Exclusion criteria

* history of substance abuse or dependence * positive urine toxicology screen or alcohol breath test * history of hypersensitivity to or allergy to any study drug * donation of blood within prior 30 days * use of analgesics, caffeine, sedatives, antidepressants, anticoagulant or antiplatelet agents within 24 hours

Design outcomes

Primary

Measure	Time frame	Description
Sum of Pain Intensity Difference From Baseline to 8 Hours	Baseline, 8 hours	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?

Secondary

Measure	Time frame	Description
Sum of Pain Relief and Intensity Differences Over 8 Hours	8 hours	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?
Sum of Pain Relief and Intensity Differences Over 2 Hours	2 hours	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?
Peak Pain Intensity Difference	24 hours	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?
Peak Pain Relief	24 hours	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?
Total Pain Relief Over 8 Hours	8 hours	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?
Duration of Analgesia	24 hours	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.
Percentage of Participants Reporting a Global Rating of Study Drug as Excellent	8 hours and 24 hours	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?
Percentage of Participants With Excellent Investigator Global Rating of Study Drug	24 hours	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?
Change From Baseline in Cognitive Assessment Using CNS-VS	Baseline (screening), 2 hours 15 minutes postdose	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.
Onset of Analgesia	8 hours	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
0.25-mg Buprenorphine HCl Buccal Film, M2 Buprenorphine HCl buccal film 0.25-mg modified formulation 2, placebo buccal film, and placebo oral capsule	31
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	30
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	31
Placebo Placebo oral capsule and 2 placebo buccal films	30
Oxycodone 5 mg Oxycodone 5-mg oral capsule and 2 placebo buccal films	31
Total	153

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Lost to Follow-up	1	0	0	0	0

Baseline characteristics

Characteristic	0.25-mg Buprenorphine HCl Buccal Film, M2	0.5-mg Buprenorphine HCl Buccal Film, M2	0.5-mg Buprenorphine HCl Buccal Film, M1	Placebo	Oxycodone 5 mg	Total
Age, Continuous	21.0 years	21.0 years	21.0 years	22.0 years	21.0 years	21.0 years
Gender Female	22 Participants	20 Participants	20 Participants	18 Participants	16 Participants	96 Participants
Gender Male	9 Participants	10 Participants	11 Participants	12 Participants	15 Participants	57 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	9 / 31	18 / 30	25 / 31	3 / 30	6 / 31
serious Total, serious adverse events	0 / 31	0 / 30	0 / 31	0 / 30	0 / 31

Outcome results

Primary

Sum of Pain Intensity Difference From Baseline to 8 Hours

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?

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
0.25-mg Buprenorphine HCl Buccal Film, M2	Sum of Pain Intensity Difference From Baseline to 8 Hours	6.016 units on a scale	Standard Deviation 19.9786
0.5-mg Buprenorphine HCl Buccal Film, M2	Sum of Pain Intensity Difference From Baseline to 8 Hours	11.867 units on a scale	Standard Deviation 20.7418
0.5-mg Buprenorphine HCl Buccal Film, M1	Sum of Pain Intensity Difference From Baseline to 8 Hours	11.282 units on a scale	Standard Deviation 22.9711
Placebo	Sum of Pain Intensity Difference From Baseline to 8 Hours	5.283 units on a scale	Standard Deviation 17.636
Oxycodone 5 mg	Sum of Pain Intensity Difference From Baseline to 8 Hours	4.290 units on a scale	Standard Deviation 14.8645

p-value: 0.473995% CI: [-5.94, 12.62]ANCOVA

p-value: 0.218395% CI: [-3.81, 16.34]ANCOVA

p-value: 0.080995% CI: [-1.11, 18.56]ANCOVA

Secondary

Change From Baseline in Cognitive Assessment Using CNS-VS

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.

Time frame: Baseline (screening), 2 hours 15 minutes postdose