A Study for Treatment of Pain in Patients With Diabetic Neuropathy.

This scale measured night pain APS scores. Data were recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

This scale measured worst pain APS scores. Data were recorded daily (preferably at bedtime) on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

This scale measured the number of participants with a 30% reduction in weekly mean 24-hour APS score from baseline to endpoint. Data were recorded daily (preferably at bedtime) on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain).

Average BPI-I measured self-reported degree of pain interference on function. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference = average of non-missing scores of individual interference items. LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

BPI-S measured self-reported severity of pain. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and current pain. LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

CGI-S measured severity of illness at the time of assessment compared with start of treatment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

PGI-I measured the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranged from 1 (very much better) to 7 (very much worse). LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

SF-MPQ consisted of 11 sensory descriptors describing pain that were rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. Three pain scores were derived from the sum of the intensity rank values of the words chosen for sensory descriptors. The SF-MPQ sensory subscale was the sum of the 11 scores (ranged from 0 to 33, with 33 being the worst). LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

ASQ consisted of 21 items (including a single item to assess overall sleep quality) and 3 subscales: Sleep Onset and Maintenance (items 1-3, 5-6, 9, 11); Sleep Experience (items 4, 7, 8, 10, 12); and Awakening Experience (items 13-20). Each item was scored on a 5-point Likert scale, ranging from 0 (no sleep at all) to 5 (a lot of sleep). Each subscale was calculated as the mean of the individual items comprising the subscale. A total ASQ score was calculated as the mean of the subscale scores; higher scores represent better sleep.

NeuroQoL had 29 items: 13 assessed specific somatic experiences (pain, lost/reduced feeling, and diffuse sensory-motor symptoms); 14 assessed specific functional, social, and emotional experiences (restrictions in daily living activities, disruptions in social relationships, and emotional distress); 2 items assessed QoL and overall satisfaction. Items reported on a 5-point scale (never/not at all to all of the time/very much). Higher mean scores=more severe symptoms/greater disruption in functioning. First 27 items also associate with 3-point bothersome/importance scale (1=none to 3=very).

The SF-36 Health Status Survey was a generic, health-related scale assessing participants' quality of life on 8 domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health) and 2 summary scores (mental component summary [MCS] and physical component summary [PCS]). MCS and PCS scores=0-100 (higher scores indicate better health status). Domain scores: general health=5-25; physical functioning=10-30; role-physical=4-8; role-emotional=3-6; social functioning=2-10; bodily pain=2-11; vitality=4-24; mental health=5-30.

The EQ-5D was a generic, multidimensional, health-related, quality-of-life instrument. The profile allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 was generated for each domain. For each participant, the outcome rating on the 5 domains was mapped to a single index through an algorithm. The index ranged between 0 and 1, with the higher score indicating a better health state perceived by the participant.

The SDS was completed by the participant and was used to assess the effect of the participant's symptoms on work/social/family life. Total scores ranged from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

Participant discontinuation in the study due to serious and other non-serious AEs was measured during both the therapy (double-blind) phase and 1-week washout (follow-up) phase. A listing of serious and other non-serious AEs is located in the Reported Adverse Event module.

The number of participants by treatment group who had abnormal high or low laboratory values was reported by the investigator and summarized as serious adverse events (SAEs) from the "Investigations" system organ class during the treatment phase of the study. A listing of SAEs is located in the Reported Adverse Event module.

Participants' systolic blood pressure and diastolic blood pressure were measured in millimeters of mercury (mmHg). LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

Pulse rate was measured in beats per minute (bpm). LS Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

The number of participants having QTcF and QTcB change ≥ 30 msec was summarized.

Percentage of participants who reported hypoglycemic (lower than normal level of blood glucose) episodes was summarized as other non-serious adverse events (AEs) from the "Investigations" system organ class (preferred term = hypoglycemia). A listing of AEs is located in the Reported Adverse Event module.

The QIDS was a 16-item patient-rated measure of depressive symptomatology. Each item had a 0 to 3 point scale. The total score ranged from 0 to 27 with higher scores indicative of greater severity. QIDS was calculated by summing the scores from the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) major depressive disorder criteria: depressed mood, loss of interest or pleasure, concentration/decision making, self outlook, suicidal ideation, energy/fatigability, sleep, weight/appetite change, and psychomotor changes.

The Columbia Suicide Severity Rating Scale (C-SSRS) captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors and ideations were provided. Suicidal behavior = a "yes" answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation = a "yes" answer to any 1 of 5 suicidal ideation questions, which included the wish to be dead and 4 different categories of active suicidal ideation.

This scale first asked if the participant was experiencing hazy or blurry vision or if he/she had difficulty focusing. If the answer was yes, follow-up questions rated the degree to which the issue impaired his/her ability to do work or to read.

Clearance is the volume of plasma cleared of study drug LY545694 (CLp) and metabolite compound 645838 (CLm) per unit time. The original PK/pharmacodynamic (PD) relationship outcome measure analysis was not conducted; therefore, only PK data were reported.

Time to response=first visit achieving a 30% reduction of weekly mean 24-hour APS score. Data were recorded daily (preferably at bedtime) on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). The number of days at which 50% of the participants at risk had at least 30% response was reported.

The total number of TEAEs (serious and non-serious) that first occurred or worsened during the treatment period) from the "Nervous system disorders" system organ class was summarized. A listing of serious AEs (SAEs) and other non-serious AEs is located in the Reported Adverse Event module.