Clinical trial NCT01485094: A Study to Assess the Safety and Efficacy of 7 Days Treatment With a Novel Analgesic in Subjects With Peripheral Neuropathic Pain
Official title: Evaluation of the Efficacy, Tolerability, and Safety of 7 Days of Treatment With GRT6010 or Pregabalin in Comparison to Placebo in Subjects With Peripheral Neuropathic Pain.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neuralgia
Keywords: neuralgia
postherpetic
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2011-12-05
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to determine whether a novel analgesic is effective in treating of neuropathic pain caused by herpetic infection, surgery, or trauma.

Detailed description: This trial evaluates the effectiveness of a novel analgesic in peripheral neuropathic pain in a mixed patient population. Participants were treated for one week and randomly assigned to the novel analgesic, pregabalin, or placebo. Pain will be characterized before and at the end of this period. This trial required the participants to stay at the investigational site for 14 consecutive days.

The enrollment visit took place Day -28 to Day -16. Participants tapered down their existing medication from Visit 2 (Day -17 to Day -5) to Visit 3 and were given rescue medication (paracetamol/acetaminophen). At Visit 3 participants were hospitalized (Day -4). The baseline evaluation period took place from Day -3 to Day -1. Randomization to one of the three treatment arms was possible after the last assessment on Day - 1 alternatively randomization took place on Day 1. This was followed by the double-blind treatment period (Day 1 to Day 7). The participants were follow-up thereafter up to day 36 (Day 34 to 38). Participants were permitted to resume their previous medication.

Eligibility criteria: Inclusion Criteria:

* Age 18 years to 75 years
* Presence of persistent neuropathic pain for at least 6 months at the time of the Enrollment Visit. Allowed reasons for neuropathic pain are: modified radical mastectomy, breast conserving surgery, or cosmetic breast surgery. \[Germany: subjects after cosmetic breast surgery may not be enrolled.\]
* Presence of "probable" or "definite" neuropathic pain.
* Presence of dynamic mechanical allodynia on the affected side, or alternatively, the mechanical pain sensitivity for any of the pinprick stimuli is higher on the affected compared to the contralateral side.
* At either Visit 5 or Visit 6: Presence of an average evoked pain intensity score of \>20 on the 0 100 point numeric rating scale (NRS) for at least 1 of the 3 clinical sub-tests for dynamic mechanical allodynia (i.e., standardized brush, cotton wool tip or cotton wisp). The average will be calculated as the arithmetic mean of all measurements per sub test. Alternatively, the arithmetic mean of the 5 test replicates for any of the pinprick stimuli for mechanical pain sensitivity is at least 3 times higher for the affected side compared to the contralateral side.
* Presence of an average ongoing pain intensity score of \>4 to \<9 on the 0-10 point numerical rating scale (NRS) without the use of rescue medication within the 3 day Baseline pain intensity evaluation Period with at least 7 of 9 assessments being present.
* Dissatisfaction with the current treatment (i.e., lack of efficacy or intolerable side effects) if taking an opioid or non opioid analgesic medication for the painful neuropathy before enrollment.

Exclusion Criteria:

* Any kind of hepatic impairment at Visit 1 or at Visit 3.
* Either active hepatitis within the past 3 months or presence of chronic hepatitis irrespective of its activity status.
* Estimated creatinine clearance of less than 60 mL/minute x 1.73 m2 at either Visit 1 or at Visit 3.
* Clinically relevant cardiac disease (e.g., unstable angina pectoris, angina pectoris Canadian Cardiovascular Society \[CCS\] Grade III to IV, acute myocardial infarction within the last 3 months, cardiac insufficiency New York Heart Association \[NYHA\] Class III to IV).
* Electrocardiogram (ECG) with clinically relevant findings at either Visit 1 or at Visit 3, including but not limited to repeated prolongation of QTc \> 450 ms (Fridericia correction), or a history of additional risk factors for torsade de pointes (e.g., family history of Long QT Syndrome).
* Clinically relevant pulmonary disease (e.g., Medical Research Council breathlessness scale of 2 or above).
* Specific antitumor therapy within the last 6 months, e.g., adjuvant radiotherapy or chemotherapy, biologics, or angiogenesis inhibitors.
* CYP2D6 poor metabolizer phenotype as predicted by CYP2D6 genotyping.
* Presence of confounding pain conditions (e.g., ulnar nerve entrapment, radial nerve injury associated with major soft-tissue or bone damage, cervico-thoracic radiculopathy, carpal tunnel syndrome, chemotherapy-induced peripheral neuropathy, or complex regional pain syndrome type I or type II).
* Phantom breast or phantom limb pain.
* Presence of exclusively negative symptoms of neuropathic pain (e.g., hypoesthesia or total anesthesia) in the affected area.

Primary outcomes:
measure: Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores
timeFrame: Baseline; Day 7 (end of double blind treatment)
measure: The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores
timeFrame: Baseline and day 7 (end of double blind treatment)
Secondary outcomes:
measure: Assessment of Responder Rates
timeFrame: Day 7 (end of double blind treatment)
measure: Onset of Current Pain Relief
timeFrame: Day 1 to Day 7 (end of double blind treatment)
measure: Onset of Ongoing Pain Relief
timeFrame: Day 1 to Day 7 (end of double blind treatment)
measure: Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1)
timeFrame: Day -1; Day 7 (end of double blind treatment)
measure: Difference in Patient's Global Impression of Change
timeFrame: Day 7 (end of double blind treatment)
measure: The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo
timeFrame: Day 7 (end of double blind treatment)
measure: Change in Area of Static Allodynia and Dynamic Allodynia From Baseline
timeFrame: Baseline; Day 7 (end of double blind treatment)
measure: Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment
timeFrame: Day 7
measure: Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7)
timeFrame: Day 7 (end of double blind treatment)
measure: Daily Current Pain Intensity
timeFrame: Baseline; Day 10
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: DEU001
city: Regensburg
country: Germany
facility: DEU002
city: Esztergom
country: Hungary
facility: HUN004
city: Győr
country: Hungary
facility: HUN003
city: Miskolc
country: Hungary
facility: HUN001
city: Szikszo
country: Hungary
facility: HUN008
city: Gdańsk
country: Poland
facility: POL002
city: Lublin
country: Poland
facility: POL004
city: Warszawa
country: Poland
facility: POL005
city: Belfast
country: United Kingdom
facility: GBR003
city: Glasgow
country: United Kingdom
facility: GBR001
city: Manchester
country: United Kingdom
facility: GBR002
Study officials:
affiliation: Grünenthal GmbH
name: Director Clinical Trials
role: STUDY_DIRECTOR
References: