Diabetes, Diabetic Peripheral Neuropathy
Conditions
Brief summary
Evaluation of the efficacy of a low and high dose of LX9211 compared to placebo in reducing pain related to diabetic peripheral neuropathy (DPNP) over an 11 week assessment period.
Interventions
DRUGLX9211
Oral Tablets
DRUGLX9211 Matching Placebo
Oral Tablets
Sponsors
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has given written informed consent to participate in the study in accordance with local regulations * Adult male and female participants ≥18 years of age at the time of screening * Body mass index ≥18.0 to ≤40.0 kg/m2 at Screening * Diagnosis of diabetic peripheral neuropathic pain (DPNP) at Screening * Pain from DPN present for at least 6 months * Haemoglobin A1C ≤11% at screening * Stable regimen for the treatment of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) for ≥1 month prior to Screening
Exclusion criteria
* Presence of other painful conditions that may confound assessment or self-evaluation of DPNP * History of major depressive episode, active, significant psychiatric disorders * History of clinically significant drug or alcohol use disorder * History of neurolytic or neurosurgical therapy for DPNP * Use of opioid medications for management of DPNP within the 2 months prior to Screening Visit * Use of non-steroidal anti-inflammatory drugs (NSAIDs) less than 2 weeks prior to the Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale | Baseline (Week 2 of the Run-in period) to Week 6 | ADPS is based on question 5 of Brief Pain Inventory (BPI)-short form for Diabetic Peripheral Neuropathy (BPI-DPN) and is assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average. on a scale of 0 to 10: 0=no pain, and 10=pain as bad as you can imagine. Higher ADPS scores indicate higher pain intensity. Negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6 | Baseline (Week 2 of the Run-in period) to Week 6 | ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average. on a scale of 0 to 10 where 0 = No Pain and 10 = pain as bad as you can imagine. If % change from Baseline ≤ (-50) then participant is considered a Responder and if missing % change from Baseline or \>(-50) then participant is considered a Non-responder. Percentage of participants who were responders (who achieved ≥50% reduction in pain intensity in ADPS from Baseline to Week 6) are reported. |
| Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Baseline (Week 2 of the Run-in period) to Week 6 | BPI-DPN: questionnaire that assesses severity of pain & its impact on functioning in participants with DPN. It consists of 4 questions that measure pain at its worst,least,average,now(current pain) on 11-point numerical scale 0=no pain;10=worst pain.Score range:0-10 for each of these pain questions, higher scores=greater pain severity. Other 7 questions of BPI evaluate level of interference of pain on daily functioning (general activity,walking,work ability,mood,enjoyment of life,relations,sleep) on 11-point numerical scale, 0=does not interfere;10=completely interferes.Score range:0-10 for each of these intensity questions, higher scores=greater interference. Pain severity & pain interference factors are reported as separate categories. Average interference score= mean of 7 interference categories collected in Questions 9A-G, only if 50% (ie at least 4 of 7) of scores were non-missing. Negative change from baseline=improvement. Score range for average interference score: 0-70. |
| Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy | Baseline (Week 2 of the Run-in period) to Week 6 | Lack of efficacy was defined as an increase of 30% from baseline in ADPS based on question 5 of the BPI-DPN. Baseline was defined as the average of the Week 2 Run-in period data collected by participants in the daily pain diary of BPI-DPN. ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale where 0 = No Pain to 10 = pain as bad as you can imagine, higher score indicates higher pain intensity. |
| Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6 | Baseline (Week 2 of the Run-in period) to Week 6 | ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average. on a scale of 0 to 10 where 0 = No Pain and 10 = pain as bad as you can imagine. If % change from Baseline ≤ (-30) then participant was considered a Responder and if missing % change from Baseline or \>(-30) participant is considered a Non-responder. Percentage of participants who were responders (who achieved ≥30% reduction in pain intensity in ADPS from Baseline to Week 6) are reported. |
| Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6 | Weeks 6 to 11 | For participants who achieved ≥30% reduction in ADPS based on Question 5 of the BPI-DPN at Week 6, the time to loss of efficacy was defined as the time from the date of Week 6 visit to the date of termination of safety follow-up due to lack of efficacy. ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | First dose of study drug after randomization up to the end of study (up to Week 11) | Adverse Events (AE) is defined as any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are defined as any AEs that occur or worsen after the first dose of study medication. |
| Patient Global Impression of Change (PGIC) Scale Score at Week 6 | Baseline (Week 2 of the Run-in period) to Week 6 | PGIC is a 7-point rating scale that assesses participant's belief about the overall improvement experienced after the end of treatment, where 1= very much improved to 7 = very much worse. Higher score indicates worsening. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at multiple investigative sites in the United States from 03 Sep 2020 to 28 Jun 2022.
Pre-assignment details
Participants with diagnosis of diabetic peripheral neuropathic pain were randomized in a 1:1:1 ratio to Placebo, LX9211 100 milligrams (mg)/10 mg and LX9211 200 mg/20 mg arm groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Following a 2-week run-in period, participants were randomized to LX9211 matching placebo received as a single loading dose, orally, on Day 1, followed by maintenance doses of LX9211 matching placebo tablets, orally, QD from Day 2 up to Week 6. Following completion of the 6-week treatment, all participants were followed for safety and received single oral tablet of LX9211 matching placebo, QD, for 5 weeks during the safety follow-up. | 107 |
| LX9211 100 mg/10 mg Following a 2-week run-in period, participants were randomized to receive a single loading dose of LX9211, 100 mg tablet, orally, on Day 1, followed by maintenance doses of LX9211 10 mg tablet, orally, QD, from Day 2 up to Week 6. Following completion of the 6-week treatment, all participants were followed for safety and received single oral tablet of LX9211 matching placebo, QD, for 5 weeks during safety follow-up. | 106 |
| LX9211 200 mg/20 mg Following a 2-week run-in period, participants were randomized to receive a single loading dose of LX9211, 200 mg orally on Day 1, followed by maintenance doses of LX9211, 20 mg, orally, QD from Day 2 up to Week 6. Following completion of the 6-week treatment, all participants were followed for safety and received single oral tablet of LX9211 matching placebo, QD, for 5 weeks during safety follow-up. | 106 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Period (Up to Week 6) | Adverse Event | 4 | 17 | 28 |
| Double-Blind Period (Up to Week 6) | Other, not specified | 0 | 2 | 2 |
| Double-Blind Period (Up to Week 6) | Subject Choice Unrelated to Adverse Event/Serious Adverse Event | 2 | 2 | 6 |
| Follow up Period (Weeks 7 to 11) | Other, not specified | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | LX9211 100 mg/10 mg | LX9211 200 mg/20 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 9.59 | 62.8 years STANDARD_DEVIATION 9.26 | 61.8 years STANDARD_DEVIATION 10.96 | 62.2 years STANDARD_DEVIATION 9.94 |
| Average Daily Pain Score (ADPS) | 6.54 score on a scale STANDARD_DEVIATION 1.154 | 6.59 score on a scale STANDARD_DEVIATION 1.091 | 6.53 score on a scale STANDARD_DEVIATION 1.028 | 6.55 score on a scale STANDARD_DEVIATION 1.089 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 13 Participants | 18 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 93 Participants | 88 Participants | 265 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 19 Participants | 22 Participants | 18 Participants | 59 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 82 Participants | 79 Participants | 83 Participants | 244 Participants |
| Sex: Female, Male Female | 41 Participants | 48 Participants | 43 Participants | 132 Participants |
| Sex: Female, Male Male | 66 Participants | 58 Participants | 63 Participants | 187 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 107 | 0 / 106 | 1 / 106 | 0 / 104 | 0 / 99 | 0 / 92 |
| other Total, other adverse events | 9 / 107 | 39 / 106 | 44 / 106 | 4 / 104 | 2 / 99 | 6 / 92 |
| serious Total, serious adverse events | 1 / 107 | 0 / 106 | 2 / 106 | 1 / 104 | 1 / 99 | 1 / 92 |
Outcome results
Primary
Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale
ADPS is based on question 5 of Brief Pain Inventory (BPI)-short form for Diabetic Peripheral Neuropathy (BPI-DPN) and is assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average. on a scale of 0 to 10: 0=no pain, and 10=pain as bad as you can imagine. Higher ADPS scores indicate higher pain intensity. Negative change from baseline indicates improvement.
Time frame: Baseline (Week 2 of the Run-in period) to Week 6
Population: The modified intent to treat (mITT) population included all randomized participants who took at least 1 dose of study drug; participants were analyzed according to their randomized treatment. 'Overall number of participants analyzed' indicates the number of participants data available for the analysis of this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale | -0.72 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale | -1.39 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale | -1.27 score on a scale |
Comparison: Mixed model repeated measures (MMRM) model included fixed effects of treatment, visit, treatment-by-week interaction, the randomization stratum of Baseline pain severity (moderate, severe), and the Baseline ADPS score as a covariate.p-value: 0.00795% CI: [-1.16, -0.18]MMRM model
Comparison: MMRM model included fixed effects of treatment, visit, treatment-by-week interaction, the randomization stratum of Baseline pain severity (moderate, severe), and the Baseline ADPS score as a covariate.p-value: 0.0395% CI: [-1.06, -0.05]MMRM model
Secondary
Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN
BPI-DPN: questionnaire that assesses severity of pain & its impact on functioning in participants with DPN. It consists of 4 questions that measure pain at its worst,least,average,now(current pain) on 11-point numerical scale 0=no pain;10=worst pain.Score range:0-10 for each of these pain questions, higher scores=greater pain severity. Other 7 questions of BPI evaluate level of interference of pain on daily functioning (general activity,walking,work ability,mood,enjoyment of life,relations,sleep) on 11-point numerical scale, 0=does not interfere;10=completely interferes.Score range:0-10 for each of these intensity questions, higher scores=greater interference. Pain severity & pain interference factors are reported as separate categories. Average interference score= mean of 7 interference categories collected in Questions 9A-G, only if 50% (ie at least 4 of 7) of scores were non-missing. Negative change from baseline=improvement. Score range for average interference score: 0-70.
Time frame: Baseline (Week 2 of the Run-in period) to Week 6
Population: The mITT population included all randomized participants who took at least 1 dose of study drug; participants were analyzed according to their randomized treatment. Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure analysis. Number analyzed indicates the number of participants evaluable for the outcome measure for the specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Normal Work | -1.01 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | General Activity | -0.77 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Sleep | -0.48 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Walking Ability | -0.74 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Mood | -0.71 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain at its Worst | -0.69 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain Right Now | -0.55 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain at its Least | -0.69 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Relations with Other People | -0.29 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Interference Score Averaged Over Questions 9A - G | -0.74 score on a scale |
| Placebo | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Enjoyment of Life | -1.03 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Mood | -0.72 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain at its Worst | -1.42 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain at its Least | -1.43 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain Right Now | -1.42 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Interference Score Averaged Over Questions 9A - G | -1.00 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | General Activity | -0.96 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Walking Ability | -1.36 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Normal Work | -1.07 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Relations with Other People | 0.14 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Sleep | -1.45 score on a scale |
| LX9211 100 mg/10 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Enjoyment of Life | -1.05 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Sleep | -1.52 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Normal Work | -1.05 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain Right Now | -1.03 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain at its Worst | -1.38 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Relations with Other People | -0.09 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Pain at its Least | -1.38 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Mood | -0.65 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | General Activity | -0.82 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Enjoyment of Life | -1.13 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Walking Ability | -1.22 score on a scale |
| LX9211 200 mg/20 mg | Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN | Interference Score Averaged Over Questions 9A - G | -0.97 score on a scale |
Comparison: Pain at its Worst: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain at its worst score as a covariate.p-value: 0.01495% CI: [-1.32, -0.15]MMRM model
Comparison: Pain at its Worst: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain at its worst score as a covariate.p-value: 0.01795% CI: [-1.27, -0.13]MMRM model
Comparison: Pain at its Least: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain at its least score as a covariate.p-value: 0.01595% CI: [-1.33, -0.15]MMRM model
Comparison: Pain at its Least: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain at its least score as a covariate.p-value: 0.0295% CI: [-1.27, -0.11]MMRM model
Comparison: Pain Right Now: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain right now score as a covariate.p-value: 0.00595% CI: [-1.48, -0.27]MMRM model
Comparison: Pain Right Now: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain right now score as a covariate.p-value: 0.11195% CI: [-1.07, 0.11]MMRM model
Comparison: Interference score averaged Over Questions 9A - G: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain interference score as a covariate.p-value: 0.39995% CI: [-0.87, 0.35]MMRM model
Comparison: Interference score averaged Over Questions 9A - G: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline pain interference score as a covariate.p-value: 0.44195% CI: [-0.83, 0.36]MMRM model
Comparison: General Activity: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline general activity score as a covariate.p-value: 0.57595% CI: [-0.87, 0.49]MMRM model
Comparison: General Activity: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline general activity score as a covariate.p-value: 0.8895% CI: [-0.71, 0.61]MMRM model
Comparison: Mood: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline mood score as a covariate.p-value: 0.97895% CI: [-0.73, 0.71]MMRM model
Comparison: Mood: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline mood score as a covariate.p-value: 0.87795% CI: [-0.65, 0.76]MMRM model
Comparison: Walking Ability: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline walking ability score as a covariate.p-value: 0.07995% CI: [-1.32, 0.07]MMRM model
Comparison: Walking Ability: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline walking ability score as a covariate.p-value: 0.16395% CI: [-1.16, 0.2]MMRM model
Comparison: Normal Work: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline normal work score as a covariate.p-value: 0.87595% CI: [-0.73, 0.62]MMRM model
Comparison: Normal Work: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline normal work score as a covariate.p-value: 0.91495% CI: [-0.69, 0.62]MMRM model
Comparison: Relations with Other People: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline relations with other people score as a covariate.p-value: 0.21995% CI: [-0.26, 1.12]MMRM model
Comparison: Relations with Other People: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline relations with other people score as a covariate.p-value: 0.55195% CI: [-0.47, 0.87]MMRM model
Comparison: Sleep: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline sleep score as a covariate.p-value: 0.00595% CI: [-1.63, -0.3]MMRM model
Comparison: Sleep: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline sleep score as a covariate.p-value: 0.00295% CI: [-1.68, -0.39]MMRM model
Comparison: Enjoyment of Life: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline enjoyment of life score as a covariate.p-value: 0.95595% CI: [-0.73, 0.69]MMRM model
Comparison: Enjoyment of Life: change from baseline was analyzed using MMRM model including fixed effects of treatment, visit, treatment-by-visit interaction, the randomization stratum of baseline pain severity (moderate, severe), and the baseline enjoyment of life score as a covariate.p-value: 0.77795% CI: [-0.79, 0.59]MMRM model
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Adverse Events (AE) is defined as any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are defined as any AEs that occur or worsen after the first dose of study medication.
Time frame: First dose of study drug after randomization up to the end of study (up to Week 11)
Population: The safety population included those participants who took at least 1 dose of study drug during the double-blind treatment period. AEs were collected and reported for treatment period and safety follow up period separately.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 32 Participants |
| LX9211 100 mg/10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 57 Participants |
| LX9211 200 mg/20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 54 Participants |
| Placebo (Single-blind Follow-up Period) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 15 Participants |
| LX9211 100 mg/10 mg (Single-blind Follow-up Period) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 21 Participants |
| LX9211 200 mg/20 mg Single-blind Follow-up Period) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 18 Participants |
Secondary
Patient Global Impression of Change (PGIC) Scale Score at Week 6
PGIC is a 7-point rating scale that assesses participant's belief about the overall improvement experienced after the end of treatment, where 1= very much improved to 7 = very much worse. Higher score indicates worsening.
Time frame: Baseline (Week 2 of the Run-in period) to Week 6
Population: The mITT population included all randomized participants who took at least 1 dose of study drug; participants were analyzed according to their randomized treatment. Overall number of participants analyzed indicates the number of participants evaluable for the analysis of the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Patient Global Impression of Change (PGIC) Scale Score at Week 6 | 3.28 score on a scale |
| LX9211 100 mg/10 mg | Patient Global Impression of Change (PGIC) Scale Score at Week 6 | 2.93 score on a scale |
| LX9211 200 mg/20 mg | Patient Global Impression of Change (PGIC) Scale Score at Week 6 | 3.13 score on a scale |
Comparison: Analysis of variance (ANOVA) model was used for the analysis with treatment and the randomization stratum of baseline pain severity (moderate, severe) as fixed covariates.p-value: 0.03195% CI: [-0.67, -0.03]ANOVA
Comparison: ANOVA model was used for the analysis with treatment and the randomization stratum of baseline pain severity (moderate, severe) as fixed covariates.p-value: 0.35195% CI: [-0.48, 0.17]ANOVA
Secondary
Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy
Lack of efficacy was defined as an increase of 30% from baseline in ADPS based on question 5 of the BPI-DPN. Baseline was defined as the average of the Week 2 Run-in period data collected by participants in the daily pain diary of BPI-DPN. ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale where 0 = No Pain to 10 = pain as bad as you can imagine, higher score indicates higher pain intensity.
Time frame: Baseline (Week 2 of the Run-in period) to Week 6
Population: The mITT population included all randomized participants who took at least 1 dose of study drug; participants were analyzed according to their randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy | 0 percentage of participants |
| LX9211 100 mg/10 mg | Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy | 0 percentage of participants |
| LX9211 200 mg/20 mg | Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy | 0 percentage of participants |
Secondary
Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6
ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average. on a scale of 0 to 10 where 0 = No Pain and 10 = pain as bad as you can imagine. If % change from Baseline ≤ (-30) then participant was considered a Responder and if missing % change from Baseline or \>(-30) participant is considered a Non-responder. Percentage of participants who were responders (who achieved ≥30% reduction in pain intensity in ADPS from Baseline to Week 6) are reported.
Time frame: Baseline (Week 2 of the Run-in period) to Week 6
Population: The mITT population included all randomized participants who took at least 1 dose of study drug; participants were analyzed according to their randomized treatment. Missing observations at Week 6 are imputed as nonresponses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6 | 17.8 percentage of participants |
| LX9211 100 mg/10 mg | Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6 | 27.4 percentage of participants |
| LX9211 200 mg/20 mg | Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6 | 17.0 percentage of participants |
Comparison: Percentage of responders were analyzed using the Cochran-Mantel-Haenszel (CMH) test stratified by the randomization factor of Baseline severity score (moderate, severe). The 95% confidence interval (CI) are calculated using the asymptotic Wald method. Missing observations at Week 6 are imputed as nonresponses.p-value: 0.09195% CI: [-1.55, 20.76]Cochran-Mantel-Haenszel
Comparison: Percentage of responders were analyzed using the CMH test stratified by the randomization factor of Baseline severity score (moderate, severe). The 95% CI are calculated using the asymptotic Wald method. Missing observations at Week 6 are imputed as nonresponses.p-value: 0.88395% CI: [-10.95, 9.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6
ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average. on a scale of 0 to 10 where 0 = No Pain and 10 = pain as bad as you can imagine. If % change from Baseline ≤ (-50) then participant is considered a Responder and if missing % change from Baseline or \>(-50) then participant is considered a Non-responder. Percentage of participants who were responders (who achieved ≥50% reduction in pain intensity in ADPS from Baseline to Week 6) are reported.
Time frame: Baseline (Week 2 of the Run-in period) to Week 6
Population: The mITT population included all randomized participants who took at least 1 dose of study drug; participants were analyzed according to their randomized treatment. Missing observations at Week 6 are imputed as nonresponses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6 | 10.3 percentage of participants |
| LX9211 100 mg/10 mg | Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6 | 15.1 percentage of participants |
| LX9211 200 mg/20 mg | Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6 | 9.4 percentage of participants |
Comparison: Percentage of responders were analyzed using the CMH test stratified by the randomization factor of Baseline severity score (moderate, severe). The 95% CI are calculated using the asymptotic Wald method. Missing observations at Week 6 are imputed as nonresponses.p-value: 0.28995% CI: [-4.11, 13.73]Cochran-Mantel-Haenszel
Comparison: Percentage of responders were analyzed using the CMH test stratified by the randomization factor of Baseline severity score (moderate, severe). The 95% CI are calculated using the asymptotic Wald method. Missing observations at Week 6 are imputed as nonresponses.p-value: 0.83795% CI: [-8.85, 7.16]Cochran-Mantel-Haenszel
Secondary
Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6
For participants who achieved ≥30% reduction in ADPS based on Question 5 of the BPI-DPN at Week 6, the time to loss of efficacy was defined as the time from the date of Week 6 visit to the date of termination of safety follow-up due to lack of efficacy. ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine.
Time frame: Weeks 6 to 11
Population: The mITT population included all randomized participants who took at least 1 dose of study drug; participants were analyzed according to their randomized treatment. Participants who had ≥30% Reduction in Pain Intensity in ADPS at Week 6 were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6 | NA weeks |
| LX9211 100 mg/10 mg | Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6 | NA weeks |
| LX9211 200 mg/20 mg | Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6 | NA weeks |