Chronic Pain Master Protocol (CPMP): A Study of LY3556050 in Participants With Chronic Low Back Pain

Study Overview
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Brief Summary
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This study is being done to test the safety and efficacy of the study drug LY3556050 for the treatment of chronic low back pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

Official Title
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Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3556050 for the Treatment of Chronic Low Back Pain

Conditions
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Chronic Low-back Pain

Intervention / Treatment
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* Drug: LY3556050
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a visual analog scale (VAS) pain value ≥40 and <95 during screening. Have a history of daily pain for at least 12 weeks based on participant report or medical history. Have a value of ≤30 on the pain catastrophizing scale. Have a body mass index <40 kilograms per meter squared (kg/m²) (inclusive). Are willing to maintain a consistent regimen of any ongoing nonpharmacologic pain-relieving therapies (for example, physical therapy) and will not start any new nonpharmacologic pain-relieving therapies during study participation. Are willing to discontinue all medications taken for chronic pain conditions for the duration of the study. Have a history of low back pain for at least 3 months located between the 12th thoracic vertebra and the lower gluteal folds, with or without radiation. Have a history of low back pain as classified by the Quebec Task Force Category 1 through 3. Have stable glycemic control as indicated by a glycated hemoglobin (HbA1c) less than or equal to 10 at time of screening. Are men, or women able to abide by reproductive and contraceptive requirements. Exclusion Criteria: Have second or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia. Have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest (for example, ablation techniques). Have surgery planned during the study for any reason, related or not to the disease state under evaluation. Have, in the judgment of the investigator, an acute, serious, or unstable medical condition or a history or presence of any other medical illness that would preclude study participation. There is an inability to rule out other causative or confounding sources of pain in the primary condition under study. Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision. Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association). Have congenital QT prolongation or QT interval corrected for heart rate using Fridericia's formula (QTcF) interval measurement >450 milliseconds (msec) for male participants, >470 msec for female participants, or >480 msec for participants with bundle branch block. Have any clinically important abnormality at screening, as determined by investigator, in physical or neurological examination, vital signs, electrocardiogram (ECG), or clinical laboratory test results that could be detrimental to the participant or could compromise the study. Have a positive human immunodeficiency virus (HIV) test result at screening. Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide. Have an intolerance to acetaminophen or paracetamol or any of its excipients. Have a history of alcohol, illicit drug, analgesic or narcotic use disorder within 2 years prior to screening. Have used a therapeutic injection (botulinum toxin or corticosteroids) in the 3 months prior to starting the washout period. Have history of or current osteoporotic compression fracture. Have had a recent major trauma (within 6 months of baseline). Have had surgical intervention for the treatment of low back pain in the past 6 months. Have a history within 2 years prior to screening or current evidence of syncope, presyncope, uncontrolled vertigo, or postural dizziness, judged to be clinically significant by the investigator. Have clinically significant active thyroid disease, including Hashimoto's thyroiditis. Are taking metformin therapy. Are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 600 Milligram (mg) LY3556050<br>Participants received 600 mg LY3556050 twice daily (BID) every 12 hours for up to 8 weeks. | Drug: LY3556050<br>* Administered orally<br>|
| Placebo Comparator: Placebo<br>Participants received placebo BID every 12 hours for up to 8 weeks. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline for Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) | The NRS was used to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95 percent (%) credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ) | The RMDQ is a simple, sensitive, and reliable method to measure disability in patients with back pain that consists of 24 statements relating to the participant's perceptions of back pain and associated disability based on physical ability/activity, sleep/rest, psychosocial, household management, eating, and pain frequency. Participants are asked if they feel the statement is descriptive of their own circumstance on that day. The total score is obtained by counting the number of ''Yes'' responses, ranging from: 0 = no disability to 24 = maximal disability. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Baseline, Week 8 | 
| Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change | Patients global impression of change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7 where, 1=very much better, and 7=very much worse. Posterior mean, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Baseline, Week 8 | 
| Change From Baseline for Worst Pain Intensity as Measured by NRS | The NRS was used to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0=no pain, and 10=pain as bad as you can imagine. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Baseline, Week 8 | 
| Change From Baseline on the Visual Analog Scale (VAS) for Pain | VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0=no pain, and 100=worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Baseline, Week 8 | 
| Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep | The MOS Sleep Scale consists of 12 questions addressing the past week. Question 1 asks time to fall asleep and it is reported in 5-point timeframe categories. Question 2 asks average hours of sleep. In the remaining 10 questions participants report how often a sleep symptom or problem was present on a scale ranging from '0=all of the time' to '5=none of the time.' MOS Sleep scale dimension scores range from 0 to 100 with lower score indicating improvement, except for the dimension of sleep adequacy, where higher scores indicate improvement. Here, the average hours of sleep (i.e., Question 2) is reported as the average number of hours slept each night during the past week (range 0 to 24 hours). Higher number of hours slept indicates improvement. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Baseline, Week 8 | 
| Total Amount of Rescue Medication Use as Measured by Average Daily Dosage | Total amount of rescue medication use as measured by average daily dosage. Posterior mean, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Week 8 | 
| Change From Baseline on the EuroQuality of Life Five Dimensions (5D) Five Level (5L) Questionnaire (EQ-5D-5L) Health State Index (United States Algorithm) | The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score using the United States algorithm. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0=a health state equivalent to death, and 1=perfect health. Posterior mean change from baseline, 95% credible intervals was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. | Baseline, Week 8 |