Trial Outcomes & Findings for Asian Phase 2 Study for Treatment of Pain Associated With Diabetic Peripheral Neuropathy (NCT NCT01504412)

NCT ID: NCT01504412

Last Updated: 2020-03-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 450 participants
• Primary outcome timeframe: Baseline to Week 7 postdose
• Results posted on: 2020-03-18

Participant Flow

Participants who met all inclusion criteria and none of the exclusion criteria were enrolled and randomized to treatment.

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.

Participant milestones

Measure	Placebo DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.	Pregabalin Pregabalin capsules 300 mg/day administered in 2 doses	DS-5565 10 mg/Day DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily).	DS-5565 20 mg/Day DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily).	DS-5565 30 mg/Day DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).
Overall Study STARTED	89	87	90	94	90
Overall Study COMPLETED	84	75	86	75	77
Overall Study NOT COMPLETED	5	12	4	19	13

Reasons for withdrawal

Measure	Placebo DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.	Pregabalin Pregabalin capsules 300 mg/day administered in 2 doses	DS-5565 10 mg/Day DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily).	DS-5565 20 mg/Day DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily).	DS-5565 30 mg/Day DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).
Overall Study Adverse Event	1	8	1	7	10
Overall Study Withdrawal by Subject	2	1	1	5	1
Overall Study Other	2	1	1	6	1
Overall Study Lost to Follow-up	0	2	0	0	0
Overall Study Lack of Efficacy	0	0	1	0	1
Overall Study Death	0	0	0	1	0

Baseline Characteristics

Asian Phase 2 Study for Treatment of Pain Associated With Diabetic Peripheral Neuropathy

Baseline characteristics by cohort

Measure	Placebo n=89 Participants DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.	Pregabalin n=87 Participants Pregabalin capsules 300 mg/day administered in 2 doses	DS-5565 10 mg/Day n=90 Participants DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily).	DS-5565 20 mg/Day n=94 Participants DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily).	DS-5565 30 mg/Day n=90 Participants DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).	Total n=450 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	64 Participants n=5 Participants	61 Participants n=7 Participants	56 Participants n=5 Participants	60 Participants n=4 Participants	69 Participants n=21 Participants	310 Participants n=8 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	26 Participants n=7 Participants	34 Participants n=5 Participants	34 Participants n=4 Participants	21 Participants n=21 Participants	140 Participants n=8 Participants
Age, Continuous	58.3 years STANDARD_DEVIATION 9.79 • n=5 Participants	60.1 years STANDARD_DEVIATION 8.74 • n=7 Participants	60.5 years STANDARD_DEVIATION 9.77 • n=5 Participants	60.9 years STANDARD_DEVIATION 9.32 • n=4 Participants	59.0 years STANDARD_DEVIATION 10.06 • n=21 Participants	59.8 years STANDARD_DEVIATION 9.55 • n=8 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	25 Participants n=7 Participants	31 Participants n=5 Participants	36 Participants n=4 Participants	41 Participants n=21 Participants	160 Participants n=8 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	62 Participants n=7 Participants	59 Participants n=5 Participants	58 Participants n=4 Participants	49 Participants n=21 Participants	290 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	89 Participants n=5 Participants	87 Participants n=7 Participants	90 Participants n=5 Participants	94 Participants n=4 Participants	90 Participants n=21 Participants	450 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	89 Participants n=5 Participants	87 Participants n=7 Participants	90 Participants n=5 Participants	94 Participants n=4 Participants	90 Participants n=21 Participants	450 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline to Week 7 postdose

Population: Mean change in ADPS was assessed in the Full Analysis Set.

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.

Outcome measures

Measure	Placebo n=88 Participants DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.	Pregabalin n=85 Participants Pregabalin capsules 300 mg/day administered in 2 doses	DS-5565 10 mg/Day n=90 Participants DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily).	DS-5565 20 mg/Day n=93 Participants DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily).	DS-5565 30 mg/Day n=90 Participants DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).
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	-0.71 units on a scale Standard Deviation 1.29	-0.69 units on a scale Standard Deviation 0.90	-0.88 units on a scale Standard Deviation 1.32	-0.60 units on a scale Standard Deviation 1.01
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	-0.92 units on a scale Standard Deviation 1.33	-1.16 units on a scale Standard Deviation 1.06	-1.21 units on a scale Standard Deviation 1.56	-1.06 units on a scale Standard Deviation 1.28
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	-1.06 units on a scale Standard Deviation 1.29	-1.32 units on a scale Standard Deviation 1.15	-1.50 units on a scale Standard Deviation 1.68	-1.35 units on a scale Standard Deviation 1.52
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	-1.29 units on a scale Standard Deviation 1.48	-1.50 units on a scale Standard Deviation 1.22	-1.65 units on a scale Standard Deviation 1.68	-1.56 units on a scale Standard Deviation 1.53
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	-1.44 units on a scale Standard Deviation 1.56	-1.62 units on a scale Standard Deviation 1.32	-1.68 units on a scale Standard Deviation 1.80	-1.47 units on a scale Standard Deviation 1.61
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	-1.40 units on a scale Standard Deviation 1.51	-1.79 units on a scale Standard Deviation 1.31	-1.78 units on a scale Standard Deviation 1.68	-1.68 units on a scale Standard Deviation 1.50
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	-1.55 units on a scale Standard Deviation 1.77	-1.82 units on a scale Standard Deviation 1.36	-1.91 units on a scale Standard Deviation 1.77	-1.75 units on a scale Standard Deviation 1.68

SECONDARY outcome

Timeframe: at Week 7 postdose

Population: Mean change in SF-MPQ VAS was assessed in the Full Analysis Set.

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.

Outcome measures

Measure	Placebo n=88 Participants DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.	Pregabalin n=85 Participants Pregabalin capsules 300 mg/day administered in 2 doses	DS-5565 10 mg/Day n=90 Participants DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily).	DS-5565 20 mg/Day n=93 Participants DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily).	DS-5565 30 mg/Day n=90 Participants DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).
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	-17.2 units on a scale Standard Error 2.06	-21.9 units on a scale Standard Error 2.01	-22.1 units on a scale Standard Error 1.97	-24.2 units on a scale Standard Error 2.00

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Pregabalin

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

DS-5565 10 mg/Day

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

DS-5565 20 mg/Day

Serious events: 4 serious events

Other events: 38 other events

Deaths: 1 deaths

DS-5565 30 mg/Day

Serious events: 2 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=88 participants at risk DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.	Pregabalin n=86 participants at risk Pregabalin capsules 300 mg/day administered in 2 doses	DS-5565 10 mg/Day n=90 participants at risk DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose.	DS-5565 20 mg/Day n=93 participants at risk DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose.	DS-5565 30 mg/Day n=90 participants at risk DS-5565 30mg/day, administered in 2 doses (15 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose.
Infections and infestations Pneumonia	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.2% 1/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Infections and infestations Bronchitis	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Infections and infestations Gastroenteritis	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Infections and infestations Osteomyelitis	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.2% 1/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Infections and infestations Urinary tract infection	1.1% 1/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph node	1.1% 1/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Psychiatric disorders Completed suicide	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Nervous system disorders Brain stem infarction	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.2% 1/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Nervous system disorders Cognitive disorder	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Eye disorders Diabetic retinopathy	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Eye disorders Vitreous haemorrhage	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Injury, poisoning and procedural complications Thermal burn	1.1% 1/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	0.00% 0/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).

Other adverse events

Measure	Placebo n=88 participants at risk DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.	Pregabalin n=86 participants at risk Pregabalin capsules 300 mg/day administered in 2 doses	DS-5565 10 mg/Day n=90 participants at risk DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose.	DS-5565 20 mg/Day n=93 participants at risk DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose.	DS-5565 30 mg/Day n=90 participants at risk DS-5565 30mg/day, administered in 2 doses (15 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose.
Infections and infestations Nasopharyngitis	3.4% 3/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	2.3% 2/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	7.8% 7/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	14.0% 13/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	3.3% 3/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Nervous system disorders Somnolence	5.7% 5/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	14.0% 12/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	8.9% 8/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	14.0% 13/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	21.1% 19/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Nervous system disorders Dizziness	3.4% 3/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	10.5% 9/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	5.6% 5/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	10.8% 10/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	16.7% 15/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Nervous system disorders Headache	2.3% 2/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	5.8% 5/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	2.2% 2/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	4.3% 4/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	3.3% 3/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Gastrointestinal disorders Vomiting	1.1% 1/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	5.8% 5/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	3.2% 3/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	2.2% 2/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
General disorders Oedema peripheral	1.1% 1/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	5.8% 5/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	3.3% 3/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	3.2% 3/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	7.8% 7/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
General disorders Gait disturbance	1.1% 1/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	4.7% 4/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	7.5% 7/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	2.2% 2/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).
Investigations Weight increased	0.00% 0/88 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	2.3% 2/86 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	1.1% 1/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	2.2% 2/93 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).	5.6% 5/90 • Adverse event data were collected from the time the Informed Consent Form was signed to 7 days after the last dose of study medication, approximately 18 months. Adverse events that appeared for the first time during treatment, or that worsened relative to the pre-treatment state, were analyzed. Additionally, 3 participants who had major violations of GCP were excluded from the Safety Analysis Set (1 participant each in the placebo, pregabalin, and in the 20-mg/day group).

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo, Inc.

Phone: +81 362251111 (M-F 9-5 JST)

Email: dsclinicaltrial@daiichisankyo.co.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place