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Buprenorphine

Phase 3

Low Back Pain | Small molecule | Pain |Collegium Pharmaceutical, Inc.|Last Updated: Feb 27, 2017

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials2
Total Enrollment1,567

FDA Designations

No designations recorded

Clinical trial landscape

Buprenorphine · 5 trials · 3 indications

Phase 3 3Phase 2 2
NCT01675167Efficacy Study to Evaluate Buprenorphine HCl Buccal Film in Opioid-Experienced SubjectsLow Back Pain
COMPLETED815 Analytics
NCT01633944Efficacy Study to Evaluate Buprenorphine HCl Buccal Film in Opioid-Naive SubjectsLow Back Pain
COMPLETED752 Analytics
NCT01256450Efficacy and Safety Study of Buprenorphine HCl Buccal Film in Subjects With Low Back PainPain
COMPLETED334 Analytics
PHASE3COMPLETED
Efficacy Study to Evaluate Buprenorphine HCl Buccal Film in Opioid-Experienced Subjects
Low Back PainUnlock trial analytics
PHASE3COMPLETED
Efficacy Study to Evaluate Buprenorphine HCl Buccal Film in Opioid-Naive Subjects
Low Back PainUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety Study of Buprenorphine HCl Buccal Film in Subjects With Low Back Pain
PainUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline to Week 12 in Average Daily Pain Intensity Scores
Baseline, week 12

Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).

Change in Pain Intensity From Baseline to Week 12
Baseline, Week 12

Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).

Number of Responders
Pre-dose (-0.5), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

A responder is defined as a subject whose maximum (across all time points) clinical opiate withdrawal scale (COWS) total score is ≥13. COWS scores range 0 to 4 or 5 on 11 items related to opiate withdrawal signs or symptoms; total score range 0 to 48 where 0-4 = no withdrawal and 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal.

Maximum COWS Total Score
Pre-dose (-0.5), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

Investigator-rated COWS scores range 0 to 4 or 5 on 11 items related to opiate withdrawal signs or symptoms; total score range 0 to 48 where 0-4 = no withdrawal and 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal. The maximum COWs total score is defined as the maximum COWs total score across all time points during the corresponding treatment period after study drug administration for each subject.

Change From Baseline in Maximum COWS Total Score
Pre-dose (-0.5; baseline), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

Investigator-rated COWS scores range 0 to 4 or 5 on 11 items related to opiate withdrawal signs or symptoms; total score range 0 to 48 where 0-4 = no withdrawal and 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal. The change from baseline in maximum COWS total score is determined as the difference between the maximum COWs total score and the baseline COWs total score.

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 Endpoints

Number of Participants With Response to Treatment (Responder) Using NRS Scale
Prior to open-label titration to week 12 in double-blind treatment
Number of Subjects With Opioid Rescue Medication Use
Week 1 to Week 12
Time to Optimal Dose of Open-label Study Medication
Up to 8 weeks in open-label titration
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Placebo Buccal FilmPLACEBO_COMPARATORTwice Daily Dosing
Buprenorphine HCl Buccal FilmEXPERIMENTALTwice Daily Dosing
PlaceboPLACEBO_COMPARATORTwice Daily Dosing
BEMA BuprenorphineEXPERIMENTALbuprenorphine buccal soluble film
BEMA PlaceboPLACEBO_COMPARATORplacebo buccal soluble film
MSE Dose Group 1EXPERIMENTALMorning and evening dose of buprenorphine HCl buccal film (300 μg) + placebo capsule in one period, and then placebo film + over-encapsulated ATC opioid (morphine sulfate or oxycodone) at 50% MSE daily dose in the alternate period
MSE Dose Group 2EXPERIMENTALMorning and evening dose of buprenorphine HCl buccal film (450 μg) + placebo capsule in one period, and then placebo film + over-encapsulated ATC opioid (morphine sulfate or oxycodone) at 50% MSE daily dose in the alternate period
Standard OpioidACTIVE_COMPARATOROxycodone 5-mg oral capsule and 2 buccal placebo films
High Dose buprenorphine HCl buccal filmEXPERIMENTALBuprenorphine HCl buccal film 0.5-mg modified formulation 1, buccal placebo film, and oral placebo capsule
Mid Dose buprenorphine HCl buccal filmEXPERIMENTALBuprenorphine HCl buccal film 0.5-mg modified formulation 2, buccal placebo film, and oral placebo capsule
Low Dose buprenorphine HCl buccal filmEXPERIMENTALBuprenorphine HCl buccal film 0.25-mg modified formulation 2, buccal placebo film, and oral placebo capsule

Interventions

NameTypeDescription
BuprenorphineDRUGBuprenorphine HCl Buccal Film at doses ranging from 150-900 mcg twice daily
PlaceboDRUGMatching Placebo Buccal Film twice daily
Placebo filmDRUGMatching placebo buccal film
OxycodoneDRUGOxycodone extended-release (ER) or immediate-release (IR) 5, 10, 15, 20, and 30 mg over-encapsulated oral tablets
Morphine sulfateDRUGMorphine sulfate 15, 30, and 60 mg ER or 15 and 30 mg IR over-encapsulated oral tablets
Placebo capsuleDRUGOral placebo capsules matching the over-encapsulated morphine sulfate and oxycodone tablets
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites66

Inclusion Criteria: * Diagnosis of moderate to severe low back pain for ≥6 months * Treating CLBP with a stable daily maintenance dose of ATC opioid analgesic medication equivalent to ≥30 mg and ≤160 mg morphine sulfate equivalents (MSE) per day for ≥4 weeks. (Additional as needed \[PRN\] analgesic...

Countries:United States
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