Phase II Clinical Trial of NPC-06 in Patients With Neuropathic Pain in Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to investigate the efficiency of pain relief and the safety of NPC-06 for the neuropathic pain associated with cancer, in addition to explore the effective concentration of NPC-06.

Detailed Description
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The eligible patients will be randomized into three groups, and will receive NPC-06 (high dose), NPC-06 (low dose) or placebo once a day for 7 days.

Official Title
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A Multicenter, Double-blind, Randomized, Placebo-controlled Parallel Group Trial to Investigate the Proof of Concept of NPC-06 in Patients With Neuropathic Pain in Cancer

Conditions
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Neuropathic Pain in Cancer

Intervention / Treatment
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* Drug: NPC-06


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 16 years old or greater at the time of informed consent Both genders Patients who can admit to hospital for all assessment duration from first administration until the next day of final administration. (including the hospitalized patient ) Patients who are diagnosed and informed as cancer (including sarcoma, lymphoma and multiple myeloma) Patients who are diagnosed as neuropathic pain by neurological examination and imaging findings Patients who NRS score of average persistent pain is higher than 4, even they were treated with level 3 of WHO three-step analgesic ladder at the observation period. Patients who NRS score at the time of first administration and NRS score of persistent pain in the past 24 hours are higher than 4. Patients who average number of daily rescue medication use during observation period is less than 6. Patients who are predicted to survive longer than 3 month. Patients who ECOG Performance Status (PS) score is 0 to 3. Patients who (or whose legally acceptable representative if the patient is underage) provide a written consent at their own will with a full understanding after receiving a sufficient explanation on participation in the study Exclusion Criteria: Patients who can not evaluate NRS by themselves. Patients who have leukemia as a complication. Patients who have a primary brain neoplasm or a metastatic brain neoplasm as a complication. Patients who have epilepsy, serious psychiatric or neurological disease ( i. e. dementia, Parkinson disease or schizophrenic disorder) or consciousness disturbance as a complication. Patients who have primary trigeminal neuralgia, diabetic neuropathy, post herpetic neuralgia or acute herpes zoster pain as a complication. Patients who has other serious pain which affect the evaluation of neuropathic pain in cancer. Patients who have sinus bradycardia or serious disturbance of conduction system. Patients who have history of hypersensitivity against hydantoin compound. Patients who are administrated tadalafil (for pulmonary hypertension), rilpivirine, asunaprevir, daclatasvir, vaniprevir, macitentan or sofosbuvir. Patients who are administrated methadone. Patients who have complications such as serious heart disease, hepatic function disorder or renal function disorder which severity are considered by investigator as grade 3 or more severe with reference to ''Concerning classification criteria for seriousness of adverse drug reactions of medical agents'' (except cancer). Patients who received surgical treatment or internal radiation therapy in past three month before the first day of pre observation period. Patients who are treated nerve block, radiation therapy, spinal cord stimulation or surgical treatment for the part of neuropathic pain in past one month before the first day of pre observation period. Patients who change the usage or dosage of medication for cancer as primal disease in the past two week before the first day of the pre observation period, or patients who are predicted not to continue the treatment without change in the medication while this clinical trial. Patients who are administrating with fosphenytoin, phenytoin or ethotoin or have taken these drugs as medication for neuropathic pain. Patients who have participated in other clinical trial and have taken a trial drug in past three month before the first day of pre observation period. Female patients who are pregnant or lactating or who may be pregnancy in the period of the clinical trial. Patients who can not agree to prevent contraception appropriately following the direction of the Investigator or the sub-investigator. Any other patients who are considered by the investigator as unsuitable for participation in the trial.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NPC-06 (High dosage)<br>18 mg (iv) in Day 1 as an induction dosage and 9 mg (iv) in Day 2 - 7 as a maintenance dosage | Drug: NPC-06<br>* Patients will receive once a day for 7 days.<br>|
| Active Comparator: NPC-06 (Low dosage)<br>15 mg (iv) in Day 1 as an induction dosage and 6 mg (iv) in Day 2 - 7 as a maintenance dosage | Drug: NPC-06<br>* Patients will receive once a day for 7 days.<br>|
| Placebo Comparator: Placebo<br>Saline will be administered intravenously | Drug: NPC-06<br>* Patients will receive once a day for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of Numeric Rating Scale (NRS) score within 2 hours after administration | Average change (slope) of NRS score | Pre-administration, 30, 60, 90 and 120 minutes post-administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other improvements of NRS score | Change of NRS score, Change of NRS score of persistent pain, Change of maximum pain, at the time of evaluation compared to baseline | Pre-dose, Days 1,2,3,4,5,6,7,8,9,10,11,12,13 | 
| Time to event | Time to event analysis of analgesic effect | 2 hours after initial administration to Day 7 | 
| Improvement of Neuropathic Pain Symptom Inventory (NPSI) score | Change of NPSI score compared to baseline | Pre-dose, Days 1,2,3,4,5,6,7,8,9,10,11,12,13 | 
| Rescue medication use | Number of times of rescue medication use | Day 1 to Day 13 | 
| Effective concentration | Blood phenytoin concentration | Day 0 to Day 13 |