Diabetic Peripheral Neuropathy, Pain
Conditions
Keywords
Pain, Diabetic Peripheral Neuropathy
Brief summary
The purpose of this study is to investigate the effectiveness and safety of DS-5565, compared to placebo, in subjects with pain associated with diabetic peripheral neuropathy.
Interventions
DRUGDS-5565
Oral tablets administered twice daily
DRUGPlacebo
DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day
Pregabalin oral capsules 150 mg administered twice a day
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 1 or Type 2 diabetes mellitus * Painful distal symmetric polyneuropathy * Average daily pain score is great than or equal to 4
Exclusion criteria
* HbA1c greater than 9.0
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 7 postdose | The mean change in average daily pain score (ADPS) was measured using a 11-point numeric rating scale (NRS; 0 \[no pain\] to 10 \[worst possible pain\]. The rating averaged over a 7-day period and was based on entries in patients' daily pain diaries. Greater mean changes (improvements) in ADPS indicated better outcomes. A minimally meaningful effect was a mean decrease of at least 1.0 point \[scale of 0 to 10\] versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | at Week 7 postdose | The Short Form-McGill Pain Questionnaire (SF-MPQ) Visual Analog Scale (VAS) is reported. For VAS, participants rated pain intensity on a 100 mm-long horizontal line, where 0 mm = no pain and 100 mm = worst possible pain. Greater mean changes (improvements) in SF-MPQ indicated better outcomes. |
Countries
Japan, South Korea, Taiwan
Participant flow
Recruitment details
Participants who met all inclusion criteria and none of the exclusion criteria were enrolled and randomized to treatment.
Pre-assignment details
Enrolled participants were equally randomized (1:1:1:1:1) to placebo, pregabalin, or one of three different doses of DS-5565 in a double-blind fashion. After randomization, participants received one-half the fixed dose for the first week, and subsequently received the fixed dose for 6 weeks. All participants were followed for an additional week.
Participants by arm
| Arm | Count |
|---|---|
| Placebo DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day. | 89 |
| Pregabalin Pregabalin capsules 300 mg/day administered in 2 doses | 87 |
| DS-5565 10 mg/Day DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily). | 90 |
| DS-5565 20 mg/Day DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily). | 94 |
| DS-5565 30 mg/Day DS-5565 30mg/day, administered in 2 doses (15 mg twice daily). | 90 |
| Total | 450 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 8 | 1 | 7 | 10 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Other | 2 | 1 | 1 | 6 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 5 | 1 |
Baseline characteristics
| Characteristic | DS-5565 20 mg/Day | DS-5565 10 mg/Day | Pregabalin | Placebo | DS-5565 30 mg/Day | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 34 Participants | 34 Participants | 26 Participants | 25 Participants | 21 Participants | 140 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 56 Participants | 61 Participants | 64 Participants | 69 Participants | 310 Participants |
| Age, Continuous | 60.9 years STANDARD_DEVIATION 9.32 | 60.5 years STANDARD_DEVIATION 9.77 | 60.1 years STANDARD_DEVIATION 8.74 | 58.3 years STANDARD_DEVIATION 9.79 | 59.0 years STANDARD_DEVIATION 10.06 | 59.8 years STANDARD_DEVIATION 9.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 90 Participants | 87 Participants | 89 Participants | 90 Participants | 450 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 94 Participants | 90 Participants | 87 Participants | 89 Participants | 90 Participants | 450 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 36 Participants | 31 Participants | 25 Participants | 27 Participants | 41 Participants | 160 Participants |
| Sex: Female, Male Male | 58 Participants | 59 Participants | 62 Participants | 62 Participants | 49 Participants | 290 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 88 | 0 / 86 | 0 / 90 | 1 / 93 | 0 / 90 |
| other Total, other adverse events | 13 / 88 | 28 / 86 | 18 / 90 | 38 / 93 | 42 / 90 |
| serious Total, serious adverse events | 3 / 88 | 2 / 86 | 1 / 90 | 4 / 93 | 2 / 90 |
Outcome results
Primary
Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy
The mean change in average daily pain score (ADPS) was measured using a 11-point numeric rating scale (NRS; 0 \[no pain\] to 10 \[worst possible pain\]. The rating averaged over a 7-day period and was based on entries in patients' daily pain diaries. Greater mean changes (improvements) in ADPS indicated better outcomes. A minimally meaningful effect was a mean decrease of at least 1.0 point \[scale of 0 to 10\] versus placebo.
Time frame: Baseline to Week 7 postdose
Population: Mean change in ADPS was assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 1 | -0.59 units on a scale | Standard Deviation 1.13 |
| Placebo | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 7 | -1.50 units on a scale | Standard Deviation 1.77 |
| Placebo | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 6 | -1.41 units on a scale | Standard Deviation 1.68 |
| Placebo | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 3 | -1.05 units on a scale | Standard Deviation 1.38 |
| Placebo | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 2 | -0.86 units on a scale | Standard Deviation 1.36 |
| Placebo | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 4 | -1.12 units on a scale | Standard Deviation 1.47 |
| Placebo | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 5 | -1.28 units on a scale | Standard Deviation 1.62 |
| Pregabalin | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 5 | -1.44 units on a scale | Standard Deviation 1.56 |
| Pregabalin | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 4 | -1.29 units on a scale | Standard Deviation 1.48 |
| Pregabalin | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 2 | -0.92 units on a scale | Standard Deviation 1.33 |
| Pregabalin | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 1 | -0.71 units on a scale | Standard Deviation 1.29 |
| Pregabalin | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 6 | -1.40 units on a scale | Standard Deviation 1.51 |
| Pregabalin | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 3 | -1.06 units on a scale | Standard Deviation 1.29 |
| Pregabalin | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 7 | -1.55 units on a scale | Standard Deviation 1.77 |
| DS-5565 10 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 4 | -1.50 units on a scale | Standard Deviation 1.22 |
| DS-5565 10 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 1 | -0.69 units on a scale | Standard Deviation 0.9 |
| DS-5565 10 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 2 | -1.16 units on a scale | Standard Deviation 1.06 |
| DS-5565 10 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 3 | -1.32 units on a scale | Standard Deviation 1.15 |
| DS-5565 10 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 5 | -1.62 units on a scale | Standard Deviation 1.32 |
| DS-5565 10 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 6 | -1.79 units on a scale | Standard Deviation 1.31 |
| DS-5565 10 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 7 | -1.82 units on a scale | Standard Deviation 1.36 |
| DS-5565 20 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 3 | -1.50 units on a scale | Standard Deviation 1.68 |
| DS-5565 20 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 5 | -1.68 units on a scale | Standard Deviation 1.8 |
| DS-5565 20 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 2 | -1.21 units on a scale | Standard Deviation 1.56 |
| DS-5565 20 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 7 | -1.91 units on a scale | Standard Deviation 1.77 |
| DS-5565 20 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 6 | -1.78 units on a scale | Standard Deviation 1.68 |
| DS-5565 20 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 1 | -0.88 units on a scale | Standard Deviation 1.32 |
| DS-5565 20 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 4 | -1.65 units on a scale | Standard Deviation 1.68 |
| DS-5565 30 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 3 | -1.35 units on a scale | Standard Deviation 1.52 |
| DS-5565 30 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 7 | -1.75 units on a scale | Standard Deviation 1.68 |
| DS-5565 30 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 6 | -1.68 units on a scale | Standard Deviation 1.5 |
| DS-5565 30 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 5 | -1.47 units on a scale | Standard Deviation 1.61 |
| DS-5565 30 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 2 | -1.06 units on a scale | Standard Deviation 1.28 |
| DS-5565 30 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 1 | -0.60 units on a scale | Standard Deviation 1.01 |
| DS-5565 30 mg/Day | Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | Baseline to Week 4 | -1.56 units on a scale | Standard Deviation 1.53 |
p-value: 0.199595% CI: [-0.99, 0.15]ANCOVA
p-value: 0.288695% CI: [-0.93, 0.2]ANCOVA
p-value: 0.470495% CI: [-0.87, 0.27]ANCOVA
Secondary
Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy
The Short Form-McGill Pain Questionnaire (SF-MPQ) Visual Analog Scale (VAS) is reported. For VAS, participants rated pain intensity on a 100 mm-long horizontal line, where 0 mm = no pain and 100 mm = worst possible pain. Greater mean changes (improvements) in SF-MPQ indicated better outcomes.
Time frame: at Week 7 postdose
Population: Mean change in SF-MPQ VAS was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | -16.7 units on a scale | Standard Error 2.03 |
| Pregabalin | Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | -17.2 units on a scale | Standard Error 2.06 |
| DS-5565 10 mg/Day | Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | -21.9 units on a scale | Standard Error 2.01 |
| DS-5565 20 mg/Day | Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | -22.1 units on a scale | Standard Error 1.97 |
| DS-5565 30 mg/Day | Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy | -24.2 units on a scale | Standard Error 2 |
Comparison: This analysis assessed placebo vs DS-5565 10 mg/day for the visual analog scale.p-value: 0.069195% CI: [-10.8, 0.4]ANCOVA
Comparison: This analysis assessed placebo vs DS-5565 20 mg/day for the visual analog scale.p-value: 0.057795% CI: [-10.9, 0.2]ANCOVA
Comparison: This analysis assessed placebo vs DS-5565 30 mg/day for the visual analog scale.p-value: 0.009395% CI: [-13, -1.8]ANCOVA