POST-HERPETIC NEURALGIA

Primary objective: To compare change in the Average Daily Pain Score (ADPS) from baseline to Week 14 in Asian subjects with PHN receiving 10 mg BID and 15 mg BID of DS-5565 versus placebo Secondary objectives: • To compare change in the ADPS from baseline to Week 14 in Asian subjects with PHN receiving 15 mg QD of DS-5565 versus placebo • To compare the ADPS responder rate (proportion of subjects with ≥ 30%, and 50% reduction from baseline to Week 14) between each arm of DS-5565 and placebo • To evaluate the effect of DS-5565 on additional pain questionnaires, including the Short-Form McGill Pain Questionnaire ([SF-MPQ]: sensory, affective and total subscales, Visual Analog Scale [VAS], and present pain intensity) and Brief Pain Inventory (Short Form) ([BPI-SF]: pain intensity, functionality, and impact of pain) • To assess the effect of DS-5565 on quality of life (QOL), mood and sleep, patient impressions in pain, allodynia, and hyperalgia • To collect blood samples for pharmacokinetic analyses • To characterize the safety and tolerability of DS-5565 based on the incidence of adverse events (AEs), discontinuations due to AEs, changes in physical findings, and results of safety monitoring

DS-5565

mirogabalin

capsule

5 mg、10 mg 和 15 mg

Primary endpoint:
• Change in ADPS from baseline to Week 14, rating
averaged daily pain score over a 7-day period, based on
entries in patients’ daily pain diaries
Secondary endpoints:
• ADPS Responder rate defined as the proportion of
subjects with ≥ 30%, and ≥ 50% reduction from baseline
to Week 14
• Change from baseline in parameters assessed using
SF-MPQ
• Change from baseline in parameters assessed using
BPI-SF (measurements of pain intensity, functionality,
and impact of pain)
• Patient Global Impression of Change (PGIC)
• Change from baseline in average daily sleep-interference
score (ADSIS)
• Change from baseline in Medical Outcomes Study
(MOS) sleep scale
• Change from baseline in the Hospital Anxiety and
Depression Scale (HADS)
• Changes from baseline in QOL, using the SF-36
• Change from baseline of allodynia and hyperalgia

Subjects must satisfy all of the following criteria to be included in the study.
1) Age ≥ 20 years at informed consent
2) Able to give written informed consent for study participation, understand procedures of
this study, and complete patient-reported questionnaires adequately
3) PHN defined as pain present for more than 3 months after herpes zoster skin rash at
screening
4) At screening, a pain scale of ≥ 40 mm on VAS of SF-MPQ
5) At randomization, a pain scale of ≥ 40 mm on VAS of SF-MPQ, and completion of at
least 4 days of daily pain diaries with an ADPS of ≥ 4 over the past 7 days
52weeks extension study:
Subjects must satisfy all of the following criteria to be included in the study.
1) Completed 14 weeks of administration in the double-blind study
2) Able to give written informed consent for study participation, understand procedure of
this study, and complete patient-reported questionnaires adequately

Subjects who meet any of the following criteria will be excluded from participation in the
study.
1) At screening, a pain scale of ≥ 90 mm on VAS of SF-MPQ
2) At randomization, a pain scale of ≥ 90 mm on VAS of SF-MPQ, or at least a daily pain
score of ≥ 9 during observation period
3) Previous use of neurolytic block (eg, chemical neurolytic block using phenol or ethyl
alcohol, radiofrequency thermocoagulation) or neurosurgical therapy for current PHN
4) Other severe pain at screening or randomization, unrelated to PHN, that may confound
the assessment of PHN
5) Neurologic disorders at screening or randomization, unrelated to PHN, that may confound
the assessment of PHN
6) Major psychiatric disorders at screening or randomization
7) Use of prohibited concomitant drugs or prohibited concomitant therapies within 7 days or
change of restricted concomitant drugs within 14 days prior to screening
8) Skin conditions that could confound the assessment of pain caused by PHN
9) Previous administration of pregabalin ≥ 300 mg/day or gabapentin ≥ 1200 mg/day,
declared lack of effect
10) Creatinine clearance (using the Cockcroft-Gault equation) < 60 mL/min at screening
11) Malignancy other than basal cell carcinoma within the past 2 years prior to screening
12) Clinically significant unstable neurologic, ophthalmologic, hepatobiliary, respiratory,
hematologic illness or unstable cardiovascular disease (eg, severe hypotension, uncontrolled
cardiac arrhythmia, or myocardial infarction) within 12 months prior to screening
13) Clinically significant findings on electrocardiogram (ECG) at screening
14) History of pernicious anemia, untreated hypothyroidism, or human immunodeficiency
virus infection
15) Known history of positive Hepatitis B antigen or Hepatitis C antibody
16) Known immunocompromised status (eg, Systemic Lupus Erythematosus, Acquired
Immune Deficiency Syndrome, patients receiving immunosuppressants due to autoimmune
disorder)
17) Pregnancy, potential pregnancy, breast feeding, or subject unwilling to take reliable
contraceptive measures during the study or for 4 weeks after study completion
18) Known hypersensitivity to pregabalin or gabapentin
19) Participation in another clinical study, either currently or within 30 days prior to
providing of informed consent
20) Experience of participating in a DS-5565 clinical study and receiving investigational
product
21) Abuse of illicit drugs or alcohol within one year prior to screening
22) Response of “yes” to any of the questions on the Columbia-Suicide Severity Rating
Scale (C-SSRS) at screening or randomization in relation to events occurring within the past
12 months
23) Previous treatment with drugs that could cause irreversible retinal degeneration
24) At screening, clinical laboratory values exceeding limits listed in Table 4-1 (see Section
4.1.3)
25) The subject who is considered inappropriate for the study at the discretion of the
investigator or sub-investigator.
52weeks extension study:
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from participation in the
study.
1) Drug compliance < 80% in the double-blind study
2) Creatinine clearance (using the Cockcroft-Gault equation) < 60 mL/min at Visit 9 of the
double-blind study
3) Experienced critical safety issue in the double-blind study
4) Known history of positive Hepatitis B antigen or Hepatitis C antibody
5) Previous treatment with drugs that could cause irreversible retinal degeneration
6) Pregnancy, potential pregnancy, breast feeding, or subject unwilling to take reliable
contraceptive measures during the study or for 4 weeks after study completion
7) The subject is considered inappropriate for the study at the discretion of the investigator
or sub-investigator