Efficacy and Safety of ETX-018810 for the Treatment of Diabetic Peripheral Neuropathic Pain

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Study to Evaluate the Efficacy and Safety of ETX 018810 in Subjects with Diabetic Peripheral Neuropathic Pain.

Detailed Description
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ETX-018810 is a new chemical entity that is under development as a non-opioid treatment for chronic pain syndromes. ETX-018810 is a prodrug of palmitoylethanolamide (PEA), an endogenous bioactive lipid that has shown efficacy in a broad range of nonclinical inflammatory and neuropathic pain models and in clinical trials in chronic pain indications, including diabetic peripheral neuropathic pain (DPNP).

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

Conditions
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Diabetic Peripheral Neuropathic Pain, Diabetic Peripheral Neuropathy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is ≥18 and ≤75 years of age at the time of signing ICF. The subject has a diagnosis of type 1 or 2 diabetes mellitus. The subject has diabetic neuropathy of a symmetrical nature in the lower extremities for ≥6 months to ≤10 years The subject reports at least moderate pain intensity The subject's onset of neuropathic pain is at least 3 months before the screening visit. The subject has used a stable regimen of antidiabetic agents for at least 1 month before the baseline visit or has achieved adequate glycemic control through diet and exercise. The subject has clinical laboratory values within normal limits or abnormal values that the investigator deems not clinically significant. Sexually active male subjects with female partners of childbearing potential and sexually active female subjects of childbearing potential must agree to practice effective contraception or to remain abstinent during the study and for 4 weeks after the last dose of investigational product The subject is capable of giving signed informed consent and agrees to provide authorization for use and release of health records. Exclusion Criteria: The subject has pain that cannot be clearly differentiated from or that could interfere with the assessment of DPNP. The subject has neurologic and/or circulatory disorders that are unrelated to diabetic neuropathy The subject has a history of hypoglycemia that disturbed consciousness or ketoacidosis that required hospitalization within the 3 months before screening. The subject has clinically significant and/or unstable renal, hepatic, hematologic, immunologic, inflammatory/rheumatologic, respiratory, or cardiovascular disease that would compromise participation in the study in the judgment of the investigator. The subject has any neurological disease that could interfere with participation in the study (eg, Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, seizures, epilepsy, stroke). The subject has an amputation of a lower extremity. Toe amputation is allowed. The subject has clinically significant abnormal electrocardiogram (ECG) findings at screening or baseline. The subject is likely to require major surgery during the study. The subject is pregnant or lactating. The subject is unwilling or unable to discontinue current medications for neuropathic pain, including topical agents. The subject is unable to refrain from using nonsteroidal anti-inflammatory drugs (NSAIDs); antiepileptic drugs, steroids, cannabinoids, or major opioids, muscle relaxants, tramadol, or tapentadol throughout the study. The subject has used prohibited nonpharmacologic therapies, including acupuncture, transcutaneous electrical nerve stimulation, etc, within 30 days before baseline/Day 1 or anticipates use of such therapies during the study.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETX-018810<br>1000 mg BID for 4 weeks | Drug: ETX-018810<br>* Study Drug<br>|
| Placebo Comparator: Placebo<br>matching placebo BID for 4 weeks | Drug: Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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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 a ≥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 | 
| 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 | 
| 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 | 
| 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 describes 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). | Baseline to Weeks 1, 2, 3 and 4 | 
| Change in the BPI - Interference Scale From Baseline to Week 4 | The BPI Interference scale 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 BPI pain scale is a composite of 4 items assessing pain severity (worst, least, average, and right now). Subjects rate their pain in 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 Daily Amount of Acetaminophen Use From Baseline to Week 4 | The daily amount of acetaminophen (rescue medication) that was used (mg per day). | Baseline to week 4 |