Safety/Efficacy Study of Retigabine vs. Placebo in Post-Herpetic Neuralgia (PHN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Valeant Pharmaceuticals International, Inc.
ClinicalTrials.gov Identifier:
NCT00612105
First received: January 25, 2008
Last updated: December 9, 2011
Last verified: November 2011
  Purpose

The purpose of the study is to evaluate the efficacy of retigabine vs. placebo in reducing pain associated with post-herpetic neuralgia.


Condition Intervention Phase
Postherpetic Neuralgia
Drug: Retigabine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Proof-of-Concept Study to Evaluate the Efficacy of Maximally Tolerated Doses of Retigabine vs. Placebo in Reducing the Pain Associated With Post-Herpetic Neuralgia

Resource links provided by NLM:


Further study details as provided by Valeant Pharmaceuticals International, Inc.:

Primary Outcome Measures:
  • Primary Endpoint Will be the Change From Baseline in Average Pain Score Over the Last 7 Days of the Maintenance Phase. [ Time Frame: Baseline and Week 4 (Maintenance Phase-MP) ] [ Designated as safety issue: No ]
    Change from Baseline (BL) was calculated as the value of the average diary pain score for the last 7 days of the MP minus the value of the average pain score at BL (post wash-out period, including the average of the last 7 available entries prior to/including the diary pain measurement on Titration Day 0). Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point Numerical Rating Scale (NRS): 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.


Secondary Outcome Measures:
  • Change From Baseline to Weeks 2 and 4 of the Maintenance Phase in Mean In-clinic Pain Assessment [ Time Frame: Baseline and Weeks 2 and 4 (Maintenance Phase - MP) ] [ Designated as safety issue: No ]
    Participants rated their pain during the previous 24 hours at all clinic visits using an 11-point Numerical Rating Scale (NRS): 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain (10=worst possible pain). Change in In-clinic Pain Assessment was calculated by subtracting the average score on the NRS at Week 2 and Week 4 (values for each week were observed cases) of the MP from the average score on the NRS at Baseline (the last non-missing measurement prior to taking study drug).

  • Number of Rescue Medication Tablets Taken Per Day During the Maintenance Phase (MP) [ Time Frame: Weeks 1, 2, 3, and 4 Maintenance Phase ] [ Designated as safety issue: No ]
    Participants recorded the number of acetaminophen tablets taken during the previous 24 hours in a participant diary. Rescue medication was summarized as the mean number of doses taken per day during each week of the Maintenance Phase (MP) and the mean number of doses taken during all MP weeks.

  • Change From Baseline in Pain Intensity Score at Each Week During the Maintenance Phase (MP) [ Time Frame: Baseline and Weeks 1, 2, 3, and 4 (MP) ] [ Designated as safety issue: No ]
    Least square mean (LSM) of pain intensity was calculated from the NRS score entered by the participants in their diaries at each week during the MP. Participants rated their pain during the previous 24 hours at all clinic visits using an NRS: 0, no pain; 1-3, mild; 4-6, moderate; 7-10 (worst possible pain), severe pain. Change from Baseline was calculated by subtracting the value of the average of the LSM of the NRS score at each week during the MP (the last 7 available diary entries in the MP were used, provided at least 3 existed) from the average Baseline value of the LSM of the NRS score.

  • Number of Participants Classified as Responders, With a 50% and 30% Pain Reduction From Baseline to the Last 7 Days of the Maintenance Phase [ Time Frame: Baseline and Week 4 Maintenance Phase (MP) ] [ Designated as safety issue: No ]
    Responders were defined as participants achieving a mean >=50% or >=30% pain reduction based on the NRS score from Baseline to the last 7 days of the MP. Those participants who did not have at least 3 diary entries in the MP, those who withdrew during the Titration Phase (TP), and non-completers (NC: who did not complete the study) were classified as non-responders. The number of responders and responders including non-completers from Baseline to the last 7 days of the MP were reported.

  • Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Medical Outcomes Study (MOS) Sleep Scale Scores [ Time Frame: Baseline and End of Maintenance Phase (MP) (Week 4). ] [ Designated as safety issue: No ]
    Change from BL (average value of MOS Sleep Scale score including Overall Sleep Problem [OSP] Index at end of MP minus average BL value) to the end of the MP was summarized for the OSP Index, in addition to the following subscales of the MOS Sleep Scale: Sleep Disturbance; Sleep Adequacy; Snoring; Awakening with Shortness of Breath or with a Headache; Somnolence; and Optimal Sleep. Each item was transformed to a scale with a range of 0-100. For each subscale, except Optimal Sleep, higher scores indicate a greater level of what was being measured (i.e., more snoring, more sleep adequacy, etc.).

  • Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Sleep Quantity [ Time Frame: Baseline and End of Maintenance Phase (MP) (Week 4). ] [ Designated as safety issue: No ]
    Change from Baseline in sleep quantity was calculated by subtracting the average value of sleep quantity, calculated in hours, at the end of the MP from the average Baseline value.

  • Number of Participants With the Indicated Change From Baseline to the End of the Maintenance Phase in Optimal Sleep Based on the Sleep Quantity Domain of the MOS Sleep Scale [ Time Frame: Baseline and End of Maintenance Phase (MP) (Week 4). ] [ Designated as safety issue: No ]
    Optimal Sleep was based on the Sleep Quantity domain of the MOS Sleep Scale and included the options of "Yes" if sleep quantity was 7-8 hours, and "No" otherwise. "Improved" indicated a change in response of no at baseline to yes at the end of the MP, "Same" indicated no change in response, and "Worse" indicated a change in response from yes at baseline to no at the end of the MP.

  • Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) [ Time Frame: Baseline to the end of Maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    For the PGIC assessment, participants were asked to assess their overall status since they initiated the study drug to the end of the Maintenance Phase using a 7-point categorical scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. All participants who completed Week 4 of the Maintenance Phase and participants who terminated early during the Maintenance Phase were assessed.

  • Mean Score on the Treatment Satisfaction Questionnaire for Medication (TSQM) at the End of the Maintenance Phase [ Time Frame: End of Maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    The TSQM assessed the participant's overall satisfaction with treatment, including subscales to assess effectiveness, side effects, convenience, and global satisfaction. Raw scores from the scale were transformed into a numeric scale ranging from 0 to 100, where higher scores indicated greater satisfaction with treatment. TSQM was reported at the end of the MP. Participants who completed Week 4 of the MP and who terminated early during the MP were assessed.

  • Scores on the Brief Pain Inventory-Short Form (BPI-SF) at the End of the MP for All Participants Who Completed Week-4 of the MP and Who Terminated Early During the MP [ Time Frame: End of Maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    The BPI-SF assessed pain intensity, pain relief from medication, and pain interference with function over the previous 24 hours. Pain intensity was assessed by the mean of 4 intensity items rated on a 0-10 categorical scale: 0=no pain, 10=pain as bad as you can imagine. Pain interference was assessed by determining the mean of the 7 interference items on a 0-10 categorical scale ranging from 0=does not interfere to 10=completely interferes. The level of pain relief provided by treatment was assessed on an 11-point categorical scale ranging from 0% to 100%

  • Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP [ Time Frame: End of Maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    Least square (LS) mean calculated based on participant's assessment of SF-36,a quality of life questionnaire consisting of 36 items grouped into 8 domains. These 8 domains further grouped into 2 overall summary measures,physical health and mental health. Higher scores on SF-36 represented better state of health. Physical/mental components summarized the data of all the physical/mental domains of SF-36 and higher scores represented better state of health.

  • Scores for Reported Health Transition at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP [ Time Frame: End of maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    The least square (LS) mean score for reported health transition was calculated based on the scores (ranging from 1 to 5) given by the participant in answer to the following question: "Compared to 1 year ago, how would you rate your health in general now?". Lower numbers represent a better state of health.

  • Number of Participants With the Indicated Responses at Baseline to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia [ Time Frame: Baseline Phase (Day -7 to Randomization Day 0) ] [ Designated as safety issue: No ]
    At Baseline, the investigator conducted the Neuropathic Pain Physical Examination (NPPE) to examine hyperalgesia and allodynia (tactile and cold). Tactile allodynia was assessed with a foam brush, based on the question:"How painful was the affected side compared to the opposite side?".

  • Number of Participants With the Indicated Responses at Baseline to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia [ Time Frame: Timeframe: Baseline Phase (Day -7 to Randomization Day 0) ] [ Designated as safety issue: No ]
    At Baseline the investigator conducted the NPPE to examine hyperalgesia and allodynia (tactile and cold). Cold threshold and allodynia was assessed to determine if a metal bar felt cool and if it felt painful, based on the questions:"Is it cool?" and "Is it painful?"

  • Number of Participants With the Indicated Responses at Baseline to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia [ Time Frame: Baseline Phase (Day -7 to Randomization Day 0) ] [ Designated as safety issue: No ]
    At Baseline the investigator conducted the NPPE to examine hyperalgesia and allodynia (tactile and cold). Hyperalgesia is defined as increased sensitivity to pain, which may be caused by damage to peripheral nerves. It was assessed with a pinprick brush, based on the questions: "How sharp was the affected side compared to the opposite side?" and "How painful was the affected side compared to the opposite side?"

  • Number of Participants With the Indicated Responses at the End of the MP to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia [ Time Frame: End of Maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    At the end of the MP, the investigator conducted the NPPE (an examination of the effect of retigabine on sensory abnormalities) to examine hyperalgesia and allodynia (tactile and cold). Tactile allodynia was assessed with a foam brush, based on the question:"How painful was the affected side compared to the opposite side?" End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

  • Number of Participants With the Indicated Responses at the End of the MP to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia [ Time Frame: End of Maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    At the end of the MP, the investigator conducted the NPPE (an examination of the effect of retigabine on sensory abnormalities) to examine hyperalgesia and allodynia (tactile and cold). Cold threshold and allodynia was assessed to determine if a metal bar felt cool and if it felt painful, based on the questions:"Is it cool?" and "Is it painful?"

  • Number of Participants With Indicated Responses at the End of the MP to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia [ Time Frame: End of Maintenance Phase (MP) (Week 4) ] [ Designated as safety issue: No ]
    At the end of the MP, the investigator conducted the NPPE (an examination of the effect of retigabine on sensory abnormalities) to examine hyperalgesia and allodynia (tactile and cold). Hyperalgesia is defined as increased sensitivity to pain, which may be caused by damage to peripheral nerves. It was assessed with a pinprick brush, based on the questions:"How sharp was the affected side compared to the opposite side?" and How painful was the affected side compared to the opposite side?"

  • Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype "Irritable Nociceptors" [ Time Frame: Baseline and Week 4 Maintenance Phase (MP) ] [ Designated as safety issue: No ]
    Participants were stratified into four different PHN subtypes based on the NPPE. Participants with pain, abnormal sensitization of the specific receptor (irritable nociceptors), and with minimal sensory loss were stratified in the"irritable nociceptors" subtype. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

  • Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype"Deafferentation Type 1 (D Type 1)" [ Time Frame: Baseline and Week 4 Maintenance Phase (MP) ] [ Designated as safety issue: No ]
    Participants stratified into 4 different PHN subtypes based on NPPE. Participants with marked sensory loss associated with severe burning pain upon slight mechanical stimuli (allodynia) were stratified in the "deafferentation type 1" subtype. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

  • Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype "Deafferentation Type 2 (D Type 2)" [ Time Frame: Baseline and Week 4 Maintenance phase (MP) ] [ Designated as safety issue: No ]
    Participants stratified into 4 different PHN subtypes based on NPPE. Participants with marked sensory loss and severe spontaneous burning pain without allodynia associated with reorganization of central nerve fibers were stratified in the "deafferentation type 2" subtype. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

  • Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype "Unclassifiable" [ Time Frame: Baseline and Week 4 Maintenance Phase (MP) ] [ Designated as safety issue: No ]
    Participants stratified into 4 different PHN subtypes based on NPPE. Participants who could not be specifically differentiated in any of the other three subtypes were stratified as "unclassifiable" meaning that the participants could not be classified into any of the predefined PHN subtypes. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.


Enrollment: 187
Study Start Date: October 2007
Study Completion Date: December 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Retigabine
Drug: Retigabine
150mg/day up to 900mg/day
Other Name: Not available
Placebo Comparator: 2
Placebo
Drug: Placebo
daily

Detailed Description:

This is a Phase 2a proof of concept study evaluating the safety/efficacy of retigabine vs. placebo in patients with post-herpetic neuralgia. After screening, patients will enter a maximum 6 week titration period followed by a 4 week maintenance period and a 3 week taper phase.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to provide informed consent
  • Male or female subjects
  • 18-85 years of age
  • PHN for more than 6 months after the healing of herpes zoster skin rash
  • Has a pain score at screening and randomization that qualifies

Exclusion Criteria:

  • Other significant pain that may potentially confound PHN pain assessment
  • Previous neurolytic or neurosurgical therapy for PHN
  • Subject has evidence of a progressive central nervous system (CNS) disease (e.g. CNS lupus, tumors, multiple sclerosis, Alzheimer's), lesion, or encephalopathy
  • Significant psychiatric or neuropsychiatric disorders including but not limited to severe depression, bipolar disorder or schizophrenia spectrum disorder, history of suicide attempt, or recent history of suicidal ideation
  • Has clinically significant abnormalities on physical examination, vital signs, ECG, or laboratory tests at the screening visit
  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: NCT00612105

  Show 45 Study Locations
Sponsors and Collaborators
Valeant Pharmaceuticals International, Inc.
Investigators
Study Director: David Lineberry Sponsor GmbH
  More Information

No publications provided

Responsible Party: Valeant Pharmaceuticals International, Inc.
ClinicalTrials.gov Identifier: NCT00612105     History of Changes
Other Study ID Numbers: VRX-RET-E22-NP201
Study First Received: January 25, 2008
Results First Received: July 8, 2011
Last Updated: December 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Valeant Pharmaceuticals International, Inc.:
Postherpetic Neuralgia, PHN, Shingles,

Additional relevant MeSH terms:
Neuralgia
Neuralgia, Postherpetic
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Diseases
Pain
Peripheral Nervous System Diseases
Signs and Symptoms
Ezogabine
Anticonvulsants
Central Nervous System Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014