Low Back Pain, Neuropathic Pain, Osteoarthritis
Conditions
Keywords
Chronic Pain, CLBP, Chronic Low Back Pain, Back Pain, Osteoarthritis, OA, Neuropathic Pain, Nerve pain, Painful neuropathy
Brief summary
The purpose of the long-terms study is to evaluate the safety, tolerability, and analgesic efficacy of EN3409 in subjects with moderate to severe chronic pain requiring continuous around-the-clock opioid analgesia for an extended period of time.
Interventions
DRUGEN3409
Open-Label Buprenorphine HCI Buccal Film at doses 300-900 mcg 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
* Female subjects who are practicing abstinence or using a medically acceptable form of contraception or have been postmenopausal, biologically sterile, or surgically sterile for more than 1 year * Male subjects who are practicing abstinence, surgically sterile, or are using a medically acceptable form of contraception * De Novo subject with a clinical diagnosis of moderate to severe noncancer-related CP (eg, CLBP, OA, neuropathic pain) for ≥ 3 months * De Novo subject that is treating their CP with a stable daily maintenance dose of ATC opioid analgesic medication equivalent to ≥ 60 mg and ≤ 160 mg Morphine Sulfate Equivalent (MSE) per day for ≥ 4 weeks * Stable health, as determined by the Principal Investigator * Subject is willing and able to comply with all protocol required visits and assessments * Rollover subject who has completed the 12-week Double-blind Treatment Phase in the EN3409-307/308 clinical study
Exclusion criteria
* A history or current evidence of any clinically significant disorder or any other condition, which in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results * Females who are pregnant, breastfeeding, or plan to become pregnant during the study * Current cancer-related pain or received chemotherapy within 6 months of screening * Subjects receiving opioid analgesic medication \< 60 mg MSE per day within 28 days of screening * De novo subjects receiving opioid analgesic medication at doses of \> 160 mg MSE per day within 28 days of screening * Subjects with a history of other chronic painful conditions, other than the index CP condition, which require frequent analgesic medication * Reflex sympathetic dystrophy or causalgia (complex regional pain syndrome), acute spinal cord compression, cauda equina compression, acute nerve root compression, meningitis, or discitis * History of allergy or contraindications to any opioid or acetaminophen * Surgical procedure for relief of pain within 6 months, or nerve/plexus block within 28 days of screening * Hypokalemia or clinically unstable cardiac disease * Moderate to severe hepatic impairment * Moderate to severe renal impairment * Current or past history of alcohol or substance * Positive urine toxicology screen for drugs of abuse * History of abnormalities on physical exam, vital signs, ECG, or lab values
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 48 in Daily Average NRS Pain Intensity Score | 48 weeks | 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 the change from baseline at week 48 is presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall All subjects combined, Roll Over and De-Novo. | 224 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Long Term Treatment | Adverse Event | 12 |
| Long Term Treatment | Lack of Efficacy | 6 |
| Long Term Treatment | Lost to Follow-up | 17 |
| Long Term Treatment | other and ongoing | 41 |
| Long Term Treatment | Protocol Violation | 10 |
| Long Term Treatment | Withdrawal by Subject | 35 |
| Screened and Taper (Rollover and DeNovo) | Any other reason and screen failures | 5 |
| Screened and Taper (Rollover and DeNovo) | Lost to Follow-up | 1 |
| Screened and Taper (Rollover and DeNovo) | Protocol Violation | 1 |
| Screened and Taper (Rollover and DeNovo) | Withdrawal by Subject | 3 |
| Titration Phase | Adverse Event | 11 |
| Titration Phase | Lack of Efficacy | 18 |
| Titration Phase | Lost to Follow-up | 2 |
| Titration Phase | Other and Continuing | 22 |
| Titration Phase | Protocol Violation | 9 |
| Titration Phase | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 31 Participants |
| Age, Categorical Between 18 and 65 years | 193 Participants |
| Age, Continuous | 52 Years STANDARD_DEVIATION 11.8 |
| BMI (kg/m^2) | 32.1 kg/m^2 STANDARD_DEVIATION 7.2 |
| Chronic Pain Lower Back Pain | 222 Participants |
| Chronic Pain Neuropathic Pain | 1 Participants |
| Chronic Pain Osteoarthritis | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 185 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height (cm) | 169.5 centimeters STANDARD_DEVIATION 10.39 |
| NRS Pain Intensity | 3 units on a scale STANDARD_DEVIATION 1.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 57 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 | 0 Participants |
| Race (NIH/OMB) White | 158 Participants |
| Sex: Female, Male Female | 125 Participants |
| Sex: Female, Male Male | 99 Participants |
| Weight (kg) | 92.2 kilograms STANDARD_DEVIATION 21.57 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 115 / 224 |
| serious Total, serious adverse events | 12 / 224 |
Outcome results
Primary
Change From Baseline to Week 48 in Daily Average NRS Pain Intensity Score
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 the change from baseline at week 48 is presented.
Time frame: 48 weeks
Population: Efficacy Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall | Change From Baseline to Week 48 in Daily Average NRS Pain Intensity Score | 0.2 units on a scale | Standard Deviation 1.78 |