Diabetic Peripheral Neuropathic Pain, Post-herpetic Neuralgia
Conditions
Keywords
Diabetic peripheral neuropathic pain, post-herpetic neuralgia, renal impairment
Brief summary
Investigate the safety and efficacy of DS-5565 in Japanese subjects with Diabetic Peripheral Neuropathic Pain (DPNP) with renal impairment or Post-Herpetic Neuralgia (PHN) with renal impairment.
Detailed description
The primary objective is the safety and tolerability of DS-5565 in Japanese subjects with moderate to severe renal impairment.
Interventions
DRUGDS-5565
DS-5565 15 mg (for moderate renal impairment) or 7.5 mg (for severe renal impairment), oral administration, Treatment period; 2-weeks titration and 12-weeks fixed dose
Sponsors
CMIC Co, Ltd. Japan
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At screening, creatinine clearance (using the Cockcroft-Gault equation): 15-59 mL/min * At screening, a pain scale of ≥ 40 mm * Type 1 or type 2 diabetes mellitus at screening (for patients with diabetic peripheral neuropathic pain DPNP only)-. Painful distal symmetric polyneuropathy (for patients with DPNP only) * post-herpetic neuralgia PHN defined as pain present for more than 3 months after herpes zoster skin rash at screening (for patients with PHN only)
Exclusion criteria
* HbA1c (National Glycohemoglobin Standardization Program) \> 10.0% (for patients with DPNP only) * Previous use of neurolytic block (for patients with PHN only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Baseline to Week 14 | Each participant recorded a pain score in the electronic patient diary once daily from the day after the screening visit (Visit 1) to the end of treatment/early termination visit (Visit 10). Prior to taking the study drug each morning, the participant selected the number that best described his or her pain over the past 24 hours on a scale of 0 (no pain) to 10 (worst possible pain). Higher ADPS scores indicated worse outcome. ADPS was the weekly average pain score based on the pain scores from the electronic patient diaries (Pain diary). In this outcome, the change from baseline in ADPS is being reported with negative values representing improvements in average daily pain. The larger the negative value (ie. improvement), the greater the improvement in average daily pain. |
Countries
Japan
Participant flow
Recruitment details
A total of 35 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study from December 2015 to March 2017 at 1 clinic site in Japan.
Participants by arm
| Arm | Count |
|---|---|
| Moderate Renal Impairment Participants with moderate RI (creatinine clearance: 30 to 59 mL/min) received DS-5565 2.5 mg BID for the first week and DS-5565 5 mg BID for the second week of the titration period and subsequently received a fixed dose of DS-5565 7.5mg BID for 12 weeks. | 30 |
| Severe Renal Impairment Participants with severe RI (creatinine clearance: 15 to 29 mL/min) received DS-5565 2.5 mg QD for the first week and DS-5565 5 mg QD for the second week of the titration period and subsequently received the fixed dose of DS-5565 7.5 mg QD for 12 weeks. | 5 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Decrease in CrCl <15 | 0 | 1 |
Baseline characteristics
| Characteristic | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 27 Participants | 5 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Continuous | 73.8 years STANDARD_DEVIATION 7.69 | 71.0 years STANDARD_DEVIATION 4.06 | 73.4 years STANDARD_DEVIATION 7.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 5 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 5 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 30 participants | 5 participants | 35 participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 24 Participants | 4 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 5 |
| other Total, other adverse events | 17 / 30 | 3 / 5 |
| serious Total, serious adverse events | 1 / 30 | 0 / 5 |
Outcome results
Primary
Change From Baseline in Average Daily Pain Score (ADPS) at Each Week
Each participant recorded a pain score in the electronic patient diary once daily from the day after the screening visit (Visit 1) to the end of treatment/early termination visit (Visit 10). Prior to taking the study drug each morning, the participant selected the number that best described his or her pain over the past 24 hours on a scale of 0 (no pain) to 10 (worst possible pain). Higher ADPS scores indicated worse outcome. ADPS was the weekly average pain score based on the pain scores from the electronic patient diaries (Pain diary). In this outcome, the change from baseline in ADPS is being reported with negative values representing improvements in average daily pain. The larger the negative value (ie. improvement), the greater the improvement in average daily pain.
Time frame: Baseline to Week 14
Population: ADPS was assessed in the All Enrolled Participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 2 | -0.37 units on a scale | Standard Deviation 0.94 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 1 | -0.14 units on a scale | Standard Deviation 0.68 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 3 | -0.85 units on a scale | Standard Deviation 1.294 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 4 | -1.13 units on a scale | Standard Deviation 1.318 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 5 | -0.90 units on a scale | Standard Deviation 1.361 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 6 | -0.92 units on a scale | Standard Deviation 1.285 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 7 | -1.22 units on a scale | Standard Deviation 1.402 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 8 | -1.29 units on a scale | Standard Deviation 1.554 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 9 | -1.36 units on a scale | Standard Deviation 1.54 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 10 | -1.33 units on a scale | Standard Deviation 1.562 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 11 | -1.43 units on a scale | Standard Deviation 1.664 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 12 | -1.59 units on a scale | Standard Deviation 1.636 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 13 | -1.84 units on a scale | Standard Deviation 1.65 |
| Moderate Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 14 | -1.90 units on a scale | Standard Deviation 1.697 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 11 | -2.07 units on a scale | Standard Deviation 1.584 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 2 | -0.50 units on a scale | Standard Deviation 0.937 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 8 | -2.04 units on a scale | Standard Deviation 1.735 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 1 | -0.20 units on a scale | Standard Deviation 0.217 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 13 | -2.25 units on a scale | Standard Deviation 1.7 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 3 | -1.83 units on a scale | Standard Deviation 1.859 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 9 | -2.21 units on a scale | Standard Deviation 1.98 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 4 | -2.07 units on a scale | Standard Deviation 2.375 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 12 | -2.10 units on a scale | Standard Deviation 1.728 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 5 | -1.89 units on a scale | Standard Deviation 2.278 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 10 | -2.32 units on a scale | Standard Deviation 1.914 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 6 | -1.82 units on a scale | Standard Deviation 1.922 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 14 | -2.52 units on a scale | Standard Deviation 2.026 |
| Severe Renal Impairment | Change From Baseline in Average Daily Pain Score (ADPS) at Each Week | Week 7 | -1.93 units on a scale | Standard Deviation 1.732 |
95% CI: [-2.45, -1.14]
95% CI: [-3.77, -0.36]