Efficacy and Safety of ETX-018810 in Subjects With Lumbosacral Radicular Pain

Study Overview
=================
Brief Summary
-----------------
Efficacy and Safety of ETX 018810 in Subjects with Lumbosacral Radicular Pain

Detailed Description
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of ETX 018810 in Subjects with Lumbosacral Radicular Pain

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of ETX-018810 in Subjects With Lumbosacral Radicular Pain

Conditions
-----------------
Lumbosacral Radiculopathy

Intervention / Treatment
-----------------
* Drug: ETX-018810
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject has pain consistent with a diagnosis of chronic lumbosacral radiculopathy due to injury of the lumbosacral nerve root(s) The subject reports at least moderate pain intensity at screening. The subject's onset of leg pain due to LSRP is at least 3 months The subject has a magnetic resonance imaging (MRI) scan that is normal or shows incidental lesions The subject has a calculated creatinine clearance ≥30 mL/min The subject has clinical laboratory values within normal limits or abnormal values that the investigator deems not clinically significant. body mass index (BMI) <40 kg/m2. Exclusion Criteria: The subject has previously undergone back surgery The subject is unable to reliably delineate or assess pain by anatomical location/distribution on a body map. The subject has a history of peripheral neuropathy, evidence of peripheral neuropathy, or evidence of mononeuropathy in the same limb of LSRP. The subject has pain due to infection/abscess, hematoma, or malignancy or other pain that may interfere with the assessment of LSRP in the legs. The subject has clinically significant and/or unstable renal, hepatic, hematologic, endocrine, immunologic, inflammatory/rheumatologic, respiratory, or cardiovascular disease that would compromise participation in the study The subject has any neurological disease that could interfere with participation in the study (e.g., Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, seizures, epilepsy, stroke). The subject has a history or current diagnosis of major psychiatric disorder(s) The subject has a has a history of substance abuse or dependence The subject has clinically significant abnormal electrocardiogram (ECG) findings The subject has received nerve blocks and/or steroid injections for LSRP within the 3 months before screening The subject is unwilling or unable to discontinue current medications for LSRP, including topical agents. The subject is unable to refrain from using prohibited meds during the study, including: NSAID, antiepileptic drugs, steroids, cannabinoids, or major opioids, antidepressants, muscle relaxants, tramadol, or tapentadol. The subject has used prohibited nonpharmacologic therapies, including acupuncture, transcutaneous electrical nerve stimulation, within 30 days the study. The subject is currently participating in another or the same clinical study or participated in another clinical study within 3 months before screening The subject is pregnant or lactating or not practicing adequate birth control

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo Controlled
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETX-018810<br>Drug: ETX-018810 BID for 4 weeks | Drug: ETX-018810<br>* Study Drug<br>|
| Placebo Comparator: Placebo<br>Matching Placebo BID for 4 weeks | Drug: Placebo<br>* Placebo<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 4 in the Weekly Average of the Daily Pain Score as Derived From the Subject's Responses on the Pain Intensity Numerical Rating Scale (PI-NRS) | Change from baseline in the weekly average of the daily pain score as derived from the subject's responses on the Pain Intensity Numerical Rating Scale (PI-NRS), a 10 point scale from 0 being the least (No Pain) to 10 being the most (Worst Possible Pain). | Baseline to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With ≥50% Reduction From Baseline to Weeks 1, 2, 3,and 4 in the Weekly Average of the Daily Pain Score | Change in the weekly average of the daily pain score as derived from the subject's responses on the Pain Intensity Numerical Rating Scale (PI-NRS), a 10 point scale from 0 being the least (No Pain) to 10 being the most (Worst Possible Pain). | Baseline to Weeks 1, 2, 3 and 4 | 
| Number of Subjects With a ≥30% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score | Change in the weekly average of the daily pain score as derived from the subject's responses on the Pain Intensity Numerical Rating Scale (PI-NRS), a 10 point scale from 0 being the least (No Pain) to 10 being the most (Worst Possible Pain). | Baseline to Weeks 1, 2, 3 and 4 | 
| Change in the Weekly Average of the Daily Pain Score From Baseline to Weeks 1, 2, and 3 | Change in the weekly average of the daily pain score as derived from the subject's responses on the Pain Intensity Numerical Rating Scale (PI-NRS), a 10 point scale from 0 being the least (No Pain) to 10 being the most (Worst Possible Pain). | Baseline to Weeks 1, 2, and 3 | 
| Change From Baseline to Week 4 for Worst Pain | The Brief Pain Inventory (BPI) includes a 'worst pain' severity scale. Subjects rate their worst pain in the last 24 hours on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). | Baseline and Week 4 | 
| Number of Subjects With a PGI-C Response (Defined as Much Improved or Very Much Improved) at Week 4 | The Patient Global Impression - Change (PGI-C) is the patient-reported counterpoint to the CGI-C (Guy, 1976). The qualitative assessment of meaningful change is determined by the patient in response to the question, Compared to your condition at the beginning of treatment, how much has your condition changed? Scores are as follows: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. | Week 4 | 
| Number of Subjects With a CGI-C Response (Defined as Much Improved or Very Much Improved) at Week 4 | The Clinical Global Impression - Change (CGI-C) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to the baseline state at the beginning of the intervention. The rater selects one response based on the following question, Compared to your patient's condition at the beginning of treatment, how much has your patient changed? Scores are as follows: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. | Week 4 | 
| Change in the Weekly Average of the Daily Sleep Score on the DSIS From Baseline to Weeks 1, 2, 3, and 4 | The Daily Sleep Interference Scale (DSIS) is an 11-point response scale that quantifies sleep interference due to pain. It is a single-item measure that is completed once daily, upon awakening, to accurately capture variability in sleep interference due to pain on a daily basis, thus minimizing recall bias. Patients are asked to select the number that best described how much their pain has interfered with their sleep during the last 24 hours on a scale from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep). The subjects were to record the value that most closely corresponded to their sleep interference over the last 24 hours in the eDiary once daily, in the morning (when the first dose of investigational medication is taken), during the baseline and 4-week treatment periods. | Baseline to Weeks 1, 2, 3 and 4 | 
| Change in BPI - Interference Scale From Baseline to Week 4 | The Brief Pain Inventory (BPI) interference score measures how much pain has interfered with seven daily activities scored on a scale from 0 (does not interfere) to 10 (completely interferes). It is scored as the mean of the seven interference items. | Baseline to Week 4 | 
| Change in the BPI - Pain Scale From Baseline to Week 4 | The Brief Pain Inventory (BPI) pain score is a composite of 4 items assessing pain severity (worst, least, average and right now). Subjects rate their pain in the last 24 hours on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). It is scored as the mean of the four pain items. | Baseline to Week 4 | 
| Change in the RMDQ From Baseline to Week 4 | The modified Roland-Morris Disability Questionnaire (RMDQ) is a self-administered, 24-question physical disability measurement assessment that evaluates the effect of back pain on functioning. Each question requires a yes or no answer; 1 point is scored for each positive response. The total scores are determined on a scale of 0 (no disability) to 24 (severe disability). | Baseline to Week 4 | 
| Change in the Daily Amount of Acetaminophen Use From Baseline to Week 4 | The daily amount of acetaminophen (rescue medication) used (mg per day). | Treatment period: 4 weeks |