Diabetic Peripheral Neuropathic Pain
Conditions
Brief summary
This study is being done to test the safety and efficacy of the study drug LY3556050 for the treatment of diabetic peripheral neuropathic pain. This trial is part of the chronic pain master protocol (H0P-MC-CPMP) which is a protocol to accelerate the development of new treatments for chronic pain.
Interventions
DRUGLY3556050
given orally
DRUGPlacebo
given orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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 pain medications taken for chronic pain conditions for the duration of the study. * Have daily symmetrical foot pain secondary to peripheral neuropathy present for at least 6 months and as diagnosed through use of the Michigan Neuropathy Screening Instrument Part B ≥3 (©University of Michigan). * Have a history and current diagnosis of type 1 or type 2 diabetes mellitus. * Have stable glycemic control as indicated by a glycated hemoglobin ≤11 at time of screening. * Are men, or women able to abide by reproductive and contraceptive requirements.
Exclusion criteria
* 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. * Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association). * Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision. * Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide. * Have a positive human immunodeficiency virus (HIV) test result at screening. * 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 a current drug-induced neuropathy, for example, due to some types of chemotherapy, or other types of peripheral neuropathy. * Have known hereditary motor, sensory or autonomic neuropathies. * 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. Metformin Exception Limited dosages of metformin are allowed in this study. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) | Baseline, Week 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change | Baseline, Week 8 | 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: 1=very much better, and 7=very much worse. 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. |
| Change From Baseline for Worst Pain Intensity as Measured by NRS | Baseline, Week 8 | 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. |
| Change From Baseline on the Visual Analog Scale (VAS) for Pain | Baseline, Week 8 | 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. |
| Change From Baseline in the Brief Pain Inventory-Short Form Modified (BPI-SFM) Total Pain Interference Score | Baseline, Week 8 | The BPI-SFM is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Pain Interference scale), and other aspects of pain (for example, location of pain, relief from medications). BPI-SFM pain interference scale has been reported here. Pain interference scale has 7 items, including general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life assessed on 10-point scale. All the 7-items are averaged to produce a total score ranging from 0 to 10 where, 0=no interfere to 10=completely interferes and the mean is reported here. Higher score represents worse outcome. 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. |
| Total Amount of Rescue Medication Use as Measured by Average Daily Dosage | Week 8 | Total amount of rescue medication use as measured by average daily dosage. 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. |
| Change From Baseline on the EuroQuality of Life Five Dimensions (5D) Five Level (5L) Questionnaire (EQ-5D-5L) Health State Index (United States Algorithm) | Baseline, Week 8 | 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 interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval. |
| Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep | Baseline, Week 8 | 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. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 600 mg LY3556050 Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks. | 45 |
| Placebo Participants received placebo BID every 12 hours for up to 8 weeks. | 23 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 3 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 8 | 5 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Sponsor's decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | 600 mg LY3556050 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.20 years STANDARD_DEVIATION 9.01 | 58.30 years STANDARD_DEVIATION 10.67 | 59.50 years STANDARD_DEVIATION 9.57 |
| Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) | 6.44 score on a scale STANDARD_DEVIATION 1.7 | 6.45 score on a scale STANDARD_DEVIATION 1.5 | 6.44 score on a scale STANDARD_DEVIATION 1.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 4 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 19 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 9 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 13 Participants | 48 Participants |
| Region of Enrollment Puerto Rico | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 44 Participants | 22 Participants | 66 Participants |
| Sex: Female, Male Female | 24 Participants | 14 Participants | 38 Participants |
| Sex: Female, Male Male | 21 Participants | 9 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 23 |
| other Total, other adverse events | 30 / 45 | 16 / 23 |
| serious Total, serious adverse events | 2 / 45 | 2 / 23 |
Outcome results
Primary
Change From Baseline in 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.
Time frame: Baseline, Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) | -2.75 score on a scale |
| Placebo | Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) | -1.19 score on a scale |
95% CI: [-2.76, -0.38]
Secondary
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: 1=very much better, and 7=very much worse. 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.
Time frame: Baseline, Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change | 2.28 score on a scale |
| Placebo | Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change | 3.19 score on a scale |
95% CI: [-1.56, -0.25]
Secondary
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.
Time frame: Baseline, Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Change From Baseline for Worst Pain Intensity as Measured by NRS | -3.06 score on a scale |
| Placebo | Change From Baseline for Worst Pain Intensity as Measured by NRS | -1.06 score on a scale |
95% CI: [-3.22, -0.77]
Secondary
Change From Baseline in the Brief Pain Inventory-Short Form Modified (BPI-SFM) Total Pain Interference Score
The BPI-SFM is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Pain Interference scale), and other aspects of pain (for example, location of pain, relief from medications). BPI-SFM pain interference scale has been reported here. Pain interference scale has 7 items, including general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life assessed on 10-point scale. All the 7-items are averaged to produce a total score ranging from 0 to 10 where, 0=no interfere to 10=completely interferes and the mean is reported here. Higher score represents worse outcome. 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.
Time frame: Baseline, Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Change From Baseline in the Brief Pain Inventory-Short Form Modified (BPI-SFM) Total Pain Interference Score | -2.31 score on a scale |
| Placebo | Change From Baseline in the Brief Pain Inventory-Short Form Modified (BPI-SFM) Total Pain Interference Score | -1.27 score on a scale |
95% CI: [-2.14, 0.08]
Secondary
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 interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.
Time frame: Baseline, Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Change From Baseline on the EuroQuality of Life Five Dimensions (5D) Five Level (5L) Questionnaire (EQ-5D-5L) Health State Index (United States Algorithm) | 0.09 score on a scale |
| Placebo | Change From Baseline on the EuroQuality of Life Five Dimensions (5D) Five Level (5L) Questionnaire (EQ-5D-5L) Health State Index (United States Algorithm) | 0.05 score on a scale |
95% CI: [-0.22, 0.29]
Secondary
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.
Time frame: Baseline, Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep | 0.30 Hours per night |
| Placebo | Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep | 0.41 Hours per night |
95% CI: [-0.86, 0.64]
Secondary
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.
Time frame: Baseline, Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Change From Baseline on the Visual Analog Scale (VAS) for Pain | -30.20 score on a scale |
| Placebo | Change From Baseline on the Visual Analog Scale (VAS) for Pain | -11.08 score on a scale |
95% CI: [-31.22, -6.97]
Secondary
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 change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.
Time frame: Week 8
Population: All enrolled participants who took at least 1 dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg LY3556050 | Total Amount of Rescue Medication Use as Measured by Average Daily Dosage | 214.28 mg per day (mg/day) |
| Placebo | Total Amount of Rescue Medication Use as Measured by Average Daily Dosage | 484.20 mg per day (mg/day) |
95% CI: [-624.98, 86.24]