Low Back Pain, Neuropathic Pain, Osteoarthritis, Pain
Conditions
Keywords
buccal soluble film
Brief summary
The purpose of this study is to determine whether BEMA Buprenorphine is safe in the treatment of chronic pain.
Detailed description
This is an open label study of up to approximately 52 weeks duration to assess the safety and effectiveness of BEMA Buprenorphine in the management of moderate to severe chronic pain. BEMA Buprenorphine is an oral transmucosal form of the opioid analgesic, buprenorphine hydrochloride, intended for application to the buccal mucosa. Buprenorphine is a synthetic opioid that is classified as a partial μ-receptor agonist and a Schedule III controlled substance in the United States.
Interventions
buccal soluble film; applied to the buccal mucosa twice daily
Sponsors
BioDelivery Sciences International
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or non-pregnant and non-nursing female aged 18 or older * History of moderate to severe chronic pain: 1. Subjects completing study BUP-301 (low back pain) or 2. Osteoarthritis or neuropathic pain, or subjects not completing study BUP-301 (low back pain), pain for ≥3 months with a pain intensity ≥5 \[11 point NRS\] reported at the titration period Day 0/1 visit following a washout period (opioids, NSAIDs, and muscle relaxants) of approximately 12 to 24 hours AND currently taking ≤60 mg oral morphine equivalent/day (including opioid-naïve) for 1 week or longer * Stable health, as determined by the Investigator, on the basis of medical history, physical examination, and laboratory results so as to comply with all study procedures * Female subjects of childbearing potential must be using a recognized effective method of birth control * Written informed consent obtained prior to any procedure being performed
Exclusion criteria
* Cancer related pain * Reflex sympathetic dystrophy or causalgia (complex regional pain syndrome), acute spinal cord compression, cauda equina compression, acute nerve root compression, meningitis, or discitis * Surgical procedure for pain within 2 months, or nerve/plexus block within 4 weeks, prior to titration period Day 0/1 visit * History of severe emesis with opioids * Clinically significant sleep apnea in the judgment of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in NRS Pain Intensity | Baseline up to approximately Week 52 | The NRS Pain intensity score is a segmented version of a visual analog scale used to measure pain. The scale is from 0 (no pain) to 10. Scores between greater than 0 and 3 are considered mild pain, scores from greater than 3 to 6 are moderate and greater than 6 to 10 are severe. The daily average is calculated and used to calculate the change from baseline at week 52. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change in Pain Intensity | Baseline to Week 28 | Patient Global Impression of Change in Pain Intensity at Week 28 as measured by a 7 point scale. Patients measure their improvement from 7='very much improved', 6='much improved', 5='minimally improved', 4='no change', 3='minimally worse', 2='much worse', 1='very much worse'. |
| Treatment Satisfaction Questionnaire for Medication/Global Satisfaction | Baseline to Week 28 | Treatment Satisfaction Questionnaire for Medication/Global Satisfaction at Week 28. Patients complete a 14 item questionaire that measures 4 scales based on side effects, effectiveness, convenience and global satisfaction. All items have either five or seven responses (except item 4), scored from one (least satisfied) to five or seven (most satisfied). The 7-item scales have a non-neutral midpoint, such that there are more positive response options than negative response options. Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100. Item 4 was not included for scoring. If an item score is missing and half of the items in the domain are complete, domain scores may be imputed from the person-specific mean score of completed items |
| Subjects Overall Satisfaction With Study Drug | Baseline to Week 52 | Subjects Overall Satisfaction with Study Drug as measured on a 5 point scale, with 1 being not satisfied and 5 being very satisified. |
| Investigator's Overall Satisfaction With Study Drug | Baseline to Week 52 | Investigator's Overall Satisfaction with Study Drug measured on a 5-point scale, with 1 being not satisfied and 5 being very satisfied. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BEMA Buproneorphine Overall buprenorphine buccal soluble film
BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily | 302 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Long-Term Treatment Period | Adverse Event | 19 |
| Long-Term Treatment Period | Lack of Efficacy | 6 |
| Long-Term Treatment Period | Lost to Follow-up | 8 |
| Long-Term Treatment Period | Other: Not Lack of Analgesic Effect | 46 |
| Long-Term Treatment Period | Physician Decision | 1 |
| Long-Term Treatment Period | Withdrawal by Subject | 19 |
| Titration Period | Adverse Event | 26 |
| Titration Period | Death | 1 |
| Titration Period | Lack of Efficacy | 21 |
| Titration Period | Lost to Follow-up | 9 |
| Titration Period | Other: Not Lack of Analgesic Effect | 8 |
| Titration Period | Physician Decision | 1 |
| Titration Period | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | BEMA Buproneorphine Overall |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 67 Participants |
| Age, Categorical Between 18 and 65 years | 235 Participants |
| Age, Continuous | 55.5 Years STANDARD_DEVIATION 12.45 |
| BMI (kg/m^2) | 32.226 kg/m^2 STANDARD_DEVIATION 6.8542 |
| Height (cm) | 169.14 centimeters STANDARD_DEVIATION 10.54 |
| NRS Pain Score | 3.3 units on a scale STANDARD_DEVIATION 1.94 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 58 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 237 Participants |
| Sex: Female, Male Female | 183 Participants |
| Sex: Female, Male Male | 119 Participants |
| Weight (kg) | 92.86 kilograms STANDARD_DEVIATION 22.25 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 302 |
| serious Total, serious adverse events | 4 / 302 |
Outcome results
Primary
Change From Baseline in NRS Pain Intensity
The NRS Pain intensity score is a segmented version of a visual analog scale used to measure pain. The scale is from 0 (no pain) to 10. Scores between greater than 0 and 3 are considered mild pain, scores from greater than 3 to 6 are moderate and greater than 6 to 10 are severe. The daily average is calculated and used to calculate the change from baseline at week 52.
Time frame: Baseline up to approximately Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BEMA Buproneorphine Overall | Change From Baseline in NRS Pain Intensity | -0.24 units on a scale | Standard Deviation 1.803 |
Secondary
Investigator's Overall Satisfaction With Study Drug
Investigator's Overall Satisfaction with Study Drug measured on a 5-point scale, with 1 being not satisfied and 5 being very satisfied.
Time frame: Baseline to Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BEMA Buproneorphine Overall | Investigator's Overall Satisfaction With Study Drug | 4.2 units on a scale | Standard Deviation 0.78 |
Secondary
Patient Global Impression of Change in Pain Intensity
Patient Global Impression of Change in Pain Intensity at Week 28 as measured by a 7 point scale. Patients measure their improvement from 7='very much improved', 6='much improved', 5='minimally improved', 4='no change', 3='minimally worse', 2='much worse', 1='very much worse'.
Time frame: Baseline to Week 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BEMA Buproneorphine Overall | Patient Global Impression of Change in Pain Intensity | 5.5 units on a scale | Standard Deviation 1.31 |
Secondary
Subjects Overall Satisfaction With Study Drug
Subjects Overall Satisfaction with Study Drug as measured on a 5 point scale, with 1 being not satisfied and 5 being very satisified.
Time frame: Baseline to Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BEMA Buproneorphine Overall | Subjects Overall Satisfaction With Study Drug | 4.1 units on a scale | Standard Deviation 0.8 |
Secondary
Treatment Satisfaction Questionnaire for Medication/Global Satisfaction
Treatment Satisfaction Questionnaire for Medication/Global Satisfaction at Week 28. Patients complete a 14 item questionaire that measures 4 scales based on side effects, effectiveness, convenience and global satisfaction. All items have either five or seven responses (except item 4), scored from one (least satisfied) to five or seven (most satisfied). The 7-item scales have a non-neutral midpoint, such that there are more positive response options than negative response options. Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100. Item 4 was not included for scoring. If an item score is missing and half of the items in the domain are complete, domain scores may be imputed from the person-specific mean score of completed items
Time frame: Baseline to Week 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BEMA Buproneorphine Overall | Treatment Satisfaction Questionnaire for Medication/Global Satisfaction | 76.6 units on a scale | Standard Deviation 15.93 |