Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Controlled Dose Finding Study of NGX-4010 for the Treatment of Painful HIV-Associated Distal Symmetrical Polyneuropathy
Brief Summary: The purpose of the study is to determine if an investigational drug, NGX-4010 (high-concentration capsaicin patch), is effective in treating painful HIV-associated neuropathy.


Options:
A: Inclusion Criteria:

* Diagnosis of PHN, with at least 6 months of pain since shingles vesicle crusting
* Average NPRS scores for PHN-associated pain during screening period of 3 to 9
* Intact, unbroken skin over the painful area(s) to be treated
* If taking chronic pain medications, be on a stable (not PRN) regimen for at least 21 days prior to Study Patch Application Visit (Day 0) and willing to maintain medications at same stable dose(s) and schedule throughout study
* Female subjects with child-bearing potential must have a negative serum beta human chorionic gonadotropin (hCG) pregnancy test, within 7 days of Study Patch Application Visit
* All subjects must be willing to use effective methods of birth control and/or refrain from participating in a conception process during the study (or, in the event of early termination from the study, for 30 days following experimental drug exposure)
* Be willing and able to comply with protocol requirements for the duration of study participation.
* Subjects must sign an informed consent form for this study approved by the Investigator's Institutional Review Board/Independent Ethics Committee (IRB/IEC).

Exclusion Criteria:

* Concomitant opioid medication, unless orally or transdermally administered and not exceeding a total daily dose of morphine 60 mg/day, or equivalent. Parenteral opioid use is excluded, regardless of dose.
* Unavailability of an effective rescue medication strategy for the subject, such as unwillingness to use opioid analgesics during study treatment, or high tolerance to opioids precluding the ability to relieve treatment-associated discomfort, as judged by Investigator.
* Active substance abuse or history of chronic substance abuse within the past year, or prior chronic substance abuse (including alcoholism) judged likely to recur during the study period by Investigator.
* Recent use (within 21 days preceding the Study Patch Application Visit \[Day 0\]) of any topically applied pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics including Lidoderm (lidocaine patch 5%), steroids or capsaicin products on the painful areas.
* Participation in a previous NeurogesX clinical trial in which subject received NGX-4010 (either blinded or open-label study treatment).
* Current use of any investigational agent, or Class 1 anti-arrhythmic drugs (such as tocainide and mexiletine).
* Diabetes mellitus, unless well-controlled as evidenced by an HbA1c level less than or equal to 9%.
* Hypertension, unless adequately controlled by medication.
* Significant pain of an etiology other than PHN. Subjects must not have significant ongoing pain from other cause(s) that may interfere with judging PHN-related pain.
* Painful PHN areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes.
* Any implanted medical device (spinal cord stimulator, intrathecal pump or peripheral nerve stimulator) for the treatment of neuropathic pain.
* Hypersensitivity to capsaicin (i.e., chili peppers or OTC capsaicin products), local anesthetics, oxycodone hydrochloride, hydrocodone bitartrate or adhesives.
* Significant ongoing or untreated abnormalities in cardiac, renal, hepatic, or pulmonary function that may interfere either with the ability to complete the study or the evaluation of adverse events.
* Recent history of a significant medical-surgical intervention in the judgment of the Investigator.
* Evidence of cognitive impairment including dementia that may interfere with subject's ability to complete daily pain diaries requiring subject's recall of average PHN pain level in the past 24 hours.
B: Inclusion Criteria:

* Diagnosis of PHN, with at least 6 months of pain since shingles vesicle crusting
* Average NPRS scores for PHN-associated pain during screening period of 3 to 9
* Intact, unbroken skin over the painful area(s) to be treated
* If taking chronic pain medications, be on a stable (not PRN) regimen for at least 21 days prior to Study Patch Application Visit (Day 0) and willing to maintain medications at same stable dose(s) and schedule throughout study
* Female subjects with child-bearing potential must have a negative serum beta human chorionic gonadotropin (hCG) pregnancy test, within 7 days of Study Patch Application Visit
* All subjects must be willing to use effective methods of birth control and/or refrain from participating in a conception process during the study (or, in the event of early termination from the study, for 30 days following experimental drug exposure)
* Be willing and able to comply with protocol requirements for the duration of study participation.
* Subjects must sign an informed consent form for this study approved by the Investigator's Institutional Review Board/Independent Ethics Committee (IRB/IEC).

Exclusion Criteria:

* Concomitant opioid medication, unless orally or transdermally administered and not exceeding a total daily dose of morphine 60 mg/day, or equivalent. Parenteral opioid use is excluded, regardless of dose.
* Unavailability of an effective rescue medication strategy for the subject, such as unwillingness to use opioid analgesics during study treatment, or high tolerance to opioids precluding the ability to relieve treatment-associated discomfort, as judged by Investigator.
* Active substance abuse or history of chronic substance abuse within the past year, or prior chronic substance abuse (including alcoholism) judged likely to recur during the study period by Investigator.
* Recent use (within 21 days preceding the Study Patch Application Visit \[Day 0\]) of any topically applied pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics including Lidoderm (lidocaine patch 5%), steroids or capsaicin products on the painful areas.
* Participation in a previous NeurogesX clinical trial in which subject received NGX-4010 (either blinded or open-label study treatment).
* Current use of any investigational agent, or Class 1 anti-arrhythmic drugs (such as tocainide and mexiletine).
* Diabetes mellitus, unless well-controlled as evidenced by an HbA1c level less than or equal to 9%.
* Hypertension, unless adequately controlled by medication.
* Significant pain of an etiology other than PHN. Subjects must not have significant ongoing pain from other cause(s) that may interfere with judging PHN-related pain.
* Painful PHN areas located on the face, above the hairline of the scalp, and/or in proximity to mucous membranes.
* Any implanted medical device (spinal cord stimulator, intrathecal pump or peripheral nerve stimulator) for the treatment of neuropathic pain.
* Hypersensitivity to capsaicin (i.e., chili peppers or OTC capsaicin products), local anesthetics, oxycodone hydrochloride, hydrocodone bitartrate or adhesives.
* Significant ongoing or untreated abnormalities or conditions, including active malignancy defined as treatment required in the last five (5) years, that in the opinion of the investigator would interfere either with the ability to complete the study or the evaluation of AEs.
* Recent history of a significant medical-surgical intervention in the judgment of the Investigator; including/not limited to major surgery or percutaneous angioplasty/coronary artery stent placement within the past 3 months, and receipt of immunosuppressive therapy within 3 months, prior to the Study Patch Application Visit \[Day 0\].
* Evidence of cognitive impairment including dementia that may interfere with subject's ability to complete daily pain diaries requiring subject's recall of average PHN pain level in the past 24 hours.
C: Inclusion Criteria:

* Patients who met the American College of Rheumatology (ACR) criteria for fibromyalgia (ie, widespread pain present for at least 3 months, and pain in at least 11 of 18 specific tender point sites)
* Patients who completed at least 4 pain diaries within the last 7 days and the average pain score must have been ≥4, and had a score of ≥40 mm on the Visual Analogue Scale (VAS) of the SF-MPQ at screening (Visit 1) and randomization (Visit 2)

Exclusion Criteria:

* Patients with other severe pain that may confound assessment or self-evaluation of the pain associated with fibromyalgia
* Patients with any inflammatory muscle or rheumatologic disease other than fibromyalgia, active infections, or untreated endocrine disorders
* Patients with severe depression
D: Inclusion Criteria:

* At least 18 years of age
* Documented evidence of HIV-1 infection
* Documented diagnosis of painful HIV-associated distal symmetrical polyneuropathy established by a neurologist resulting from HIV disease and/or antiretroviral drug exposure, with primary symptoms of pain, burning or dysesthetic discomfort in both feet for at least 2 months prior to Screening Visit, and absent or diminished ankle reflexes, and at least one of the following: distal diminution of vibration sensation or pain or temperature sensation in the legs
* Either no neurotoxic antiretroviral (didanosine, zalcitabine or stavudine) exposure for at least 8 weeks prior to Screening Visit, or currently on stable dose(s) of any neurotoxic antiretroviral(s) for at least 8 weeks prior to Screening Visit
* Screening Pain Sum Score of 12 to 36
* Karnofsky Performance Score of greater than or equal to 60
* Intact, unbroken skin over the painful area(s) to be treated
* If taking chronic pain medications, be on a stable (not PRN) regimen for at least 21 days prior to Treatment Visit and willing to maintain these medications at the same stable dose(s) and schedule throughout the study
* Female subjects with child-bearing potential: negative serum pregnancy test performed at Screening Visit
* Willing to use effective methods of birth control and/or refrain from participating in a conception process during study and for 30 days following experimental drug exposure
* Willing and able to comply with protocol requirements for duration of study

Exclusion Criteria:

* Concomitant opioid medication, unless orally or transdermally administered and not exceeding a total daily dose of morphine 60 mg/day, or equivalent. Parenteral opioid use is excluded, regardless of dose
* Unavailability of an effective rescue medication strategy for the subject, such as unwillingness to use opioid analgesics during treatment, or high tolerance to opioids precluding the ability to relieve treatment-associated discomfort with Roxicodone® or Vicodin®, as judged by the Investigator
* Active substance abuse or history of chronic substance abuse within the past year, or prior chronic substance abuse judged likely to recur during the study period by the investigator
* Recent use (within 21 days preceding the Treatment Visit of any topically applied pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics (including Lidoderm®), steroids or capsaicin products on the painful areas
* Current use of any investigational agent or Class 1 anti-arrhythmic drugs
* Significant pain of an etiology other than painful HIV-associated neuropathy; significant ongoing pain from other cause(s) that may interfere with judging HIV-associated neuropathy pain
* Evidence of another contributing cause for peripheral neuropathy, e.g., diabetes mellitus requiring medication control (i.e., oral hypoglycemics, insulin); hereditary neuropathy; vitamin B12 deficiency (B12 level ≤ 200 pg/mL) or less than 3 months of B12 supplementation prior to Screening Visit; or treatment within 90 days prior to Screening Visit with any drug that may have contributed to the sensory neuropathy
* Any implanted medical device (spinal cord stimulator, intrathecal pump or peripheral nerve stimulator) for the treatment of neuropathic pain
* Treatment for acute opportunistic infections within 14 days before Treatment Visit
* Presence of acute, active opportunistic infection, except oral thrush; oral, genital, or rectal herpes; and Mycobacterium avium bacteremia within 2 weeks prior to Screening Visit
* Currently have active malignant disease
* Significant ongoing or untreated abnormalities in cardiac, renal, hepatic, or pulmonary function that may interfere either with the ability to complete the study or the evaluation of adverse events
* Hypersensitivity to capsaicin (i.e., chili peppers or OTC capsaicin products), local anesthetics, Roxicodone®, Vicodin®, or adhesives

Answer: D