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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01504412
Recruitment Status : Completed
First Posted : January 5, 2012
Results First Posted : March 18, 2020
Last Update Posted : March 18, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Pain
Diabetic Peripheral Neuropathy
Interventions Drug: DS-5565
Drug: Placebo
Drug: Pregabalin capsules
Enrollment 450
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.
Arm/Group Title Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day
Hide Arm/Group Description DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day. Pregabalin capsules 300 mg/day administered in 2 doses DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily). DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily). DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).
Period Title: Overall Study
Started 89 87 90 94 90
Completed 84 75 86 75 77
Not Completed 5 12 4 19 13
Reason Not Completed
Adverse Event             1             8             1             7             10
Withdrawal by Subject             2             1             1             5             1
Other             2             1             1             6             1
Lost to Follow-up             0             2             0             0             0
Lack of Efficacy             0             0             1             0             1
Death             0             0             0             1             0
Arm/Group Title Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day Total
Hide Arm/Group Description DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day. Pregabalin capsules 300 mg/day administered in 2 doses DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily). DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily). DS-5565 30mg/day, administered in 2 doses (15 mg twice daily). Total of all reporting groups
Overall Number of Baseline Participants 89 87 90 94 90 450
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 89 participants 87 participants 90 participants 94 participants 90 participants 450 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
64
  71.9%
61
  70.1%
56
  62.2%
60
  63.8%
69
  76.7%
310
  68.9%
>=65 years
25
  28.1%
26
  29.9%
34
  37.8%
34
  36.2%
21
  23.3%
140
  31.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 89 participants 87 participants 90 participants 94 participants 90 participants 450 participants
58.3  (9.79) 60.1  (8.74) 60.5  (9.77) 60.9  (9.32) 59.0  (10.06) 59.8  (9.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 89 participants 87 participants 90 participants 94 participants 90 participants 450 participants
Female
27
  30.3%
25
  28.7%
31
  34.4%
36
  38.3%
41
  45.6%
160
  35.6%
Male
62
  69.7%
62
  71.3%
59
  65.6%
58
  61.7%
49
  54.4%
290
  64.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 89 participants 87 participants 90 participants 94 participants 90 participants 450 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
89
 100.0%
87
 100.0%
90
 100.0%
94
 100.0%
90
 100.0%
450
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 89 participants 87 participants 90 participants 94 participants 90 participants 450 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
89
 100.0%
87
 100.0%
90
 100.0%
94
 100.0%
90
 100.0%
450
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Mean Change in Average Daily Pain Score From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Mean change in ADPS was assessed in the Full Analysis Set.
Arm/Group Title Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day
Hide Arm/Group Description:
DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.
Pregabalin capsules 300 mg/day administered in 2 doses
DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily).
DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily).
DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).
Overall Number of Participants Analyzed 88 85 90 93 90
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline to Week 1 -0.59  (1.13) -0.71  (1.29) -0.69  (0.90) -0.88  (1.32) -0.60  (1.01)
Baseline to Week 2 -0.86  (1.36) -0.92  (1.33) -1.16  (1.06) -1.21  (1.56) -1.06  (1.28)
Baseline to Week 3 -1.05  (1.38) -1.06  (1.29) -1.32  (1.15) -1.50  (1.68) -1.35  (1.52)
Baseline to Week 4 -1.12  (1.47) -1.29  (1.48) -1.50  (1.22) -1.65  (1.68) -1.56  (1.53)
Baseline to Week 5 -1.28  (1.62) -1.44  (1.56) -1.62  (1.32) -1.68  (1.80) -1.47  (1.61)
Baseline to Week 6 -1.41  (1.68) -1.40  (1.51) -1.79  (1.31) -1.78  (1.68) -1.68  (1.50)
Baseline to Week 7 -1.50  (1.77) -1.55  (1.77) -1.82  (1.36) -1.91  (1.77) -1.75  (1.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, DS-5565 10 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1995
Comments Dunnett method was used for adjustment of multiple testing.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.99 to 0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, DS-5565 20 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2886
Comments Dunnett method was used for adjustment of multiple testing.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.93 to 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, DS-5565 30 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4704
Comments Dunnett method was used for adjustment of multiple testing.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.87 to 0.27
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change in Short Form-McGill Pain Questionnaire From Baseline Among Participants Who Received DS5565 for Pain Associated With Diabetic Peripheral Neuropathy
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Mean change in SF-MPQ VAS was assessed in the Full Analysis Set.
Arm/Group Title Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day
Hide Arm/Group Description:
DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day.
Pregabalin capsules 300 mg/day administered in 2 doses
DS-5565 10 mg/day, administered in 2 doses (5 mg twice daily).
DS-5565 20 mg/day, administered in 2 doses (10 mg twice daily).
DS-5565 30mg/day, administered in 2 doses (15 mg twice daily).
Overall Number of Participants Analyzed 88 85 90 93 90
Mean (Standard Error)
Unit of Measure: units on a scale
-16.7  (2.03) -17.2  (2.06) -21.9  (2.01) -22.1  (1.97) -24.2  (2.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, DS-5565 10 mg/Day
Comments This analysis assessed placebo vs DS-5565 10 mg/day for the visual analog scale.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0691
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -5.2
Confidence Interval (2-Sided) 95%
-10.8 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, DS-5565 20 mg/Day
Comments This analysis assessed placebo vs DS-5565 20 mg/day for the visual analog scale.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0577
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -5.4
Confidence Interval (2-Sided) 95%
-10.9 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, DS-5565 30 mg/Day
Comments This analysis assessed placebo vs DS-5565 30 mg/day for the visual analog scale.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0093
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -7.4
Confidence Interval (2-Sided) 95%
-13.0 to -1.8
Estimation Comments [Not Specified]
Time Frame 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 Event Reporting Description 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).
 
Arm/Group Title Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day
Hide Arm/Group Description DS-5565 placebo oral tablets and pregabalin placebo oral capsules administered 2 times per day. Pregabalin capsules 300 mg/day administered in 2 doses 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, administered in 2 doses (10 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose. DS-5565 30mg/day, administered in 2 doses (15 mg twice daily). Treatment period: 1 week titration and 6 weeks of fixed dose.
All-Cause Mortality
Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/88 (0.00%)   0/86 (0.00%)   0/90 (0.00%)   1/93 (1.08%)   0/90 (0.00%) 
Hide Serious Adverse Events
Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/88 (3.41%)   2/86 (2.33%)   1/90 (1.11%)   4/93 (4.30%)   2/90 (2.22%) 
Eye disorders           
Diabetic retinopathy  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/93 (1.08%)  0/90 (0.00%) 
Vitreous haemorrhage  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/93 (0.00%)  0/90 (0.00%) 
Infections and infestations           
Pneumonia  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  1/93 (1.08%)  0/90 (0.00%) 
Bronchitis  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  0/93 (0.00%)  1/90 (1.11%) 
Gastroenteritis  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/93 (1.08%)  0/90 (0.00%) 
Osteomyelitis  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/93 (0.00%)  0/90 (0.00%) 
Urinary tract infection  1  1/88 (1.14%)  0/86 (0.00%)  0/90 (0.00%)  0/93 (0.00%)  0/90 (0.00%) 
Injury, poisoning and procedural complications           
Thermal burn  1  1/88 (1.14%)  0/86 (0.00%)  0/90 (0.00%)  0/93 (0.00%)  0/90 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Metastases to lymph node  1  1/88 (1.14%)  0/86 (0.00%)  0/90 (0.00%)  0/93 (0.00%)  0/90 (0.00%) 
Nervous system disorders           
Brain stem infarction  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/93 (0.00%)  0/90 (0.00%) 
Cognitive disorder  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  0/93 (0.00%)  1/90 (1.11%) 
Psychiatric disorders           
Completed suicide  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/93 (1.08%)  0/90 (0.00%) 
1
Term from vocabulary, MedDRA (16.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Pregabalin DS-5565 10 mg/Day DS-5565 20 mg/Day DS-5565 30 mg/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/88 (14.77%)   28/86 (32.56%)   18/90 (20.00%)   38/93 (40.86%)   42/90 (46.67%) 
Gastrointestinal disorders           
Vomiting  1  1/88 (1.14%)  5/86 (5.81%)  1/90 (1.11%)  3/93 (3.23%)  2/90 (2.22%) 
General disorders           
Oedema peripheral  1  1/88 (1.14%)  5/86 (5.81%)  3/90 (3.33%)  3/93 (3.23%)  7/90 (7.78%) 
Gait disturbance  1  1/88 (1.14%)  4/86 (4.65%)  1/90 (1.11%)  7/93 (7.53%)  2/90 (2.22%) 
Infections and infestations           
Nasopharyngitis  1  3/88 (3.41%)  2/86 (2.33%)  7/90 (7.78%)  13/93 (13.98%)  3/90 (3.33%) 
Investigations           
Weight increased  1  0/88 (0.00%)  2/86 (2.33%)  1/90 (1.11%)  2/93 (2.15%)  5/90 (5.56%) 
Nervous system disorders           
Somnolence  1  5/88 (5.68%)  12/86 (13.95%)  8/90 (8.89%)  13/93 (13.98%)  19/90 (21.11%) 
Dizziness  1  3/88 (3.41%)  9/86 (10.47%)  5/90 (5.56%)  10/93 (10.75%)  15/90 (16.67%) 
Headache  1  2/88 (2.27%)  5/86 (5.81%)  2/90 (2.22%)  4/93 (4.30%)  3/90 (3.33%) 
1
Term from vocabulary, MedDRA (16.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Contact for Clinical Trial Information
Organization: Daiichi Sankyo, Inc.
Phone: +81 362251111 (M-F 9-5 JST)
EMail: dsclinicaltrial@daiichisankyo.co.jp
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
ClinicalTrials.gov Identifier: NCT01504412    
Other Study ID Numbers: DS5565-A-J202
First Submitted: January 3, 2012
First Posted: January 5, 2012
Results First Submitted: February 4, 2020
Results First Posted: March 18, 2020
Last Update Posted: March 18, 2020