A Confirmatory Study of Fentanyl in Participants With Post-herpetic Neuralgia, Complex Regional Pain Syndrome or Postoperative Pain Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01008553
First received: November 5, 2009
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to evaluate the efficacy and safety of fentanyl in opioid-naive participants with post-herpetic neuralgia, complex regional pain syndrome or post-operative pain syndrome who cannot obtain a sufficient analgesic effect by the treatment of non-opioid analgesics (drug used to control pain).


Condition Intervention Phase
Postherpetic Neuralgia
Complex Regional Pain Syndromes (CRPS)
Postoperative Pain
Drug: Fentanyl
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Verification Study of JNS020QD in Patients With Post-herpetic Neuralgia, Complex Regional Pain Syndrome (CRPS) or Postoperative Pain Syndrome

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy [ Time Frame: Day 1 up to Day 85 (double-blind period) and Day 92 (discontinuation of the study) ] [ Designated as safety issue: No ]
    Time from start of double-blind (researchers and participants were unaware of the treatment) period to withdrawal because of insufficient analgesic efficacy based on any of the pre-defined discontinuation criteria was noted.


Secondary Outcome Measures:
  • Pain Visual Analog Scale (VAS) Score - Titration Period [ Time Frame: Day 12-14 (Screening period) and Day 27-29 (Titration period) ] [ Designated as safety issue: No ]
    The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a "100-millimeter (mm) VAS scale" by drawing a slash. The left margin (0 mm) was considered "No pain at all", and the right margin (100 mm) was considered "Severer pain than this is inconceivable". The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of Screening period and during 3 days before the end of titration period was reported.

  • Pain Visual Analog Scale (VAS) Score - Double-Blind Period [ Time Frame: Day 27-29 (Titration period) and Day 83-85 (double-blind period) ] [ Designated as safety issue: No ]
    The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a "100-millimeter (mm) VAS scale" by drawing a slash. The left margin (0 mm) was considered "No pain at all", and the right margin (100 mm) was considered "Severer pain than this is inconceivable". The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of titration period and during 3 days before the end of double-blind period was reported.

  • Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period [ Time Frame: Day 1 and 29 or final evaluation (Titration period) ] [ Designated as safety issue: No ]
    The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: "Extremely satisfied", "Satisfied", "Neither satisfied nor dissatisfied", "Dissatisfied" and "Dissatisfied very much". The results were reported as Category 1 = At least "Neither satisfied nor dissatisfied", which included participants with general evaluation of "Extremely satisfied" to "Neither satisfied nor dissatisfied", and Category 2 = At least "Satisfied", which included participants with general evaluation of "Extremely satisfied" to "Satisfied".

  • Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period [ Time Frame: Day 1 and 85 or final evaluation (double-blind period) ] [ Designated as safety issue: No ]
    The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: "Extremely satisfied", "Satisfied", "Neither satisfied nor dissatisfied", "Dissatisfied" and "Dissatisfied very much". The results were reported as Category 1 = At least "Neither satisfied nor dissatisfied", which included participants with general evaluation of "Extremely satisfied" to "Neither satisfied nor dissatisfied", and Category 2 = At least "Satisfied", which included participants with general evaluation of "Extremely satisfied" to "Satisfied".

  • Number of Doses of Rescue Treatment Per Day - Titration Period [ Time Frame: Day 1 and 29 or final evaluation (Titration period) ] [ Designated as safety issue: No ]
    If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary.

  • Number of Doses of Rescue Treatment Per Day - Double-Blind Period [ Time Frame: Day 1 and 85 or final evaluation (double-blind period) ] [ Designated as safety issue: No ]
    If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary.

  • Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period [ Time Frame: Day 1 and 29 or final evaluation (Titration period) ] [ Designated as safety issue: No ]
    The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions [questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 [questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)]). Total score ranges from 0 to 10 with higher values indicating more pain.

  • Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period [ Time Frame: Day 1 and 85 or final evaluation (double-blind period) ] [ Designated as safety issue: No ]
    The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions [questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 [questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)]). Total score ranges from 0 to 10 with higher values indicating more pain.

  • Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period [ Time Frame: Day 1 and 29 or final evaluation (Titration period) ] [ Designated as safety issue: No ]
    The SF-36v2 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state.

  • Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period [ Time Frame: Day 1 and 85 or final evaluation (double-blind period) ] [ Designated as safety issue: No ]
    The SF-36v2 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state.

  • Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period [ Time Frame: Day 29 or final evaluation (Titration period) ] [ Designated as safety issue: No ]
    Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective.

  • Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period [ Time Frame: Day 1 and 85 or final evaluation (double-blind period) ] [ Designated as safety issue: No ]
    Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective.


Enrollment: 258
Study Start Date: December 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fentanyl (Titration period)
One-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which will be increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) score of the participants. The dose will be increased up to maximum of 50 mcg/hr. The treatment will continue for 10-29 days and then the eligible participants from this group will be randomly assigned to either of the two groups in the double-blind period.
Drug: Fentanyl
One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm and thigh and replaced every day.
Experimental: Fentanyl (Double-blind period)
Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, will be administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which will be same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will be continued for 12 weeks.
Drug: Fentanyl
One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm and thigh and replaced every day.
Placebo Comparator: Placebo (Double-blind period)
Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, will be administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) will be gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo will be gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will continue for 12 weeks.
Drug: Placebo
Placebo patch indistinguishable from one-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm and thigh and replaced every day.

Detailed Description:

This is a multi-center (conducted in more than one center), double-blind (neither the participant nor the physician knows the assigned study drug), randomized (participants assigned study drug by chance), withdrawal study in opioid-naive participants with post-herpetic neuralgia (intense, typically intermittent pain along the course of a nerve caused by the varicella zoster virus), complex regional pain syndrome or post-operative pain syndrome. The study will consist of titration period (10-29 days) and double-blind period (12 weeks) and the visits will include Day 5-7, 8, 15, 22, 29 in titration period and Day 2-4, 8, 15, 22, 29, 43, 57, 71 and 85 in double-blind period. All the eligible participants will receive one-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) of either fentanyl at the dose ranging from 12.5 to 50 microgram/hour or matching placebo. Efficacy will be evaluated primarily by time to withdrawal due to insufficient analgesic efficacy. Participants' safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants whose pain because of post-herpetic neuralgia, Complex Regional Pain Syndrome (CRPS) or post-operative pain syndrome is continuing for at least 12 weeks prior to informed consent
  • Participants who are continuously taking a non-opioid analgesic at the normal highest dose or more for at least 14 consecutive days prior to informed consent, or at a certain dose (except the use on an as-needed base) on consecutive days or participants who are continuously taking an analgesic adjuvant with a certain dosage and administration (except the use on an as-needed base) for at least 14 consecutive days prior to informed consent
  • Participants showing insufficient therapeutic efficacy of the non-opioid analgesic currently being used, and to requiring a continuous opioid analgesic as per the Investigator or Sub-investigator
  • Participants with an average pain intensity of 50 millimeter or more on the Visual Analog Scale in 24-hour daily living prior to informed consent
  • Participants who can be hospitalized to the 4th day after the initiation of titration period

Exclusion Criteria:

  • Participants who had an operation that may affect the assessment within 30 days before informed consent
  • Participants whose main cause of the pain to be assessed is considered attributable to psychogenic pain (physical pain that is caused, increased, or prolonged by mental, emotional, or behavioral factors)
  • Participants with asthma, bradyarrhythmia (slow irregular heart beat) and severe respiratory function disorders
  • Participants complicated with hepatic dysfunction such as fulminant hepatitis (inflammation of the liver) and liver cirrhosis (serious liver disorder in which connective tissue replaces normal liver tissue, and liver failure often occurs), or renal impairment such as nephritic syndrome, acute renal failure, and chronic renal failure
  • Participants with a history of hypersensitivity to fentanyl and other opioid analgesics
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01008553

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Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01008553     History of Changes
Other Study ID Numbers: CR015544, JNS020QD-JPN-N02
Study First Received: November 5, 2009
Results First Received: March 21, 2013
Last Updated: June 19, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Postherpetic Neuralgia
Complex Regional Pain Syndromes (CRPS)
Postoperative Pain
Fentanyl
Patch, transdermal
Opioid analgesics

Additional relevant MeSH terms:
Syndrome
Pain, Postoperative
Complex Regional Pain Syndromes
Pain
Somatoform Disorders
Neuralgia
Neuralgia, Postherpetic
Disease
Pathologic Processes
Postoperative Complications
Signs and Symptoms
Mental Disorders
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Autonomic Nervous System Diseases
Fentanyl
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Adjuvants, Anesthesia
Anesthetics, Intravenous

ClinicalTrials.gov processed this record on September 18, 2014