Long-term Open-Label Safety Study to Evaluate EN3409

Study Overview
=================
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.

Official Title
-----------------
A Phase 3, Open-label, Long-term Study to Evaluate the Safety, Tolerability, and Analgesic Efficacy of BEMA® Buprenorphine in Subjects With Moderate to Severe Chronic Pain Requiring Continuous Around-the-Clock Opioid Analgesia for an Extended Period of Time

Conditions
-----------------
Low Back Pain, Osteoarthritis, Neuropathic Pain

Intervention / Treatment
-----------------
* Drug: EN3409


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EN3409<br>Buprenorphine HCI Buccal File at doses ranging from 300-900 mcg twice daily | Drug: EN3409<br>* Open-Label Buprenorphine HCI Buccal Film at doses 300-900 mcg twice daily<br>* Other names: Buprenorphine HCI Buccal Film 300-900 mcg twice daily;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 48 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Pain, CLBP, Chronic Low Back Pain, Back Pain, Osteoarthritis, OA, Neuropathic Pain, Nerve pain, Painful neuropathy