A Study to Assess the Safety and Efficacy of 7 Days Treatment With a Novel Analgesic in Subjects With Peripheral Neuropathic Pain

NCT01485094 | Terminated Phase 2 Results

• 2 other identifiers: 9671652011-002092-42
• Study Type: interventional
• Target: 114
• Locations: 4 countries
• Sites: 12

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.

Conditions

Neuralgia

Keywords

neuralgia; postherpetic

Outcome Measures

Primary Outcomes (2)

• Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores

  The baseline pain intensity score was calculated as a mean of pain intensity scores during the Baseline Period (from Day -3 to Day -1). The ongoing pain intensity data from Day-3 to Day 7 was used. For the analysis, only pain scores on days where participants received study drug were considered. The primary efficacy analysis of the ongoing pain intensity score were analyzed in a Bayesian framework, via a mono exponential decay model, with the baseline Numeric Rating Score (NRS) as intercept. Considering the inclusion criteria of baseline pain intensity being in the range from 4 to 9, the range in ongoing pain intensity difference between baseline and end-of-double-blind treatment can be from 6 (worst possible value) to -9 (best possible value). A negative value indicates improvement whilst on the treatment.

  Baseline; Day 7 (end of double blind treatment)

• The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores

  The difference between baseline and end-of-double-blind treatment brush-evoked pain intensity scores compared to placebo on a 0-100 point NRS (measured as part of the dynamic mechanical allodynia assessments). Each participant rated each brush-evoked pain intensity on a 0 to 100 point Numerical Pain Rating Scale, with 0 indicating 'No Pain' and 100 indicating 'most intense pain imaginable'. Lower values compared to an individual subject's baseline are an improvement in symptoms. The baseline brush-evoked pain intensity score was defined as the average of the geometric mean of all of the values obtained on Day -2 and Day -1, and compared with the scores obtained on day 6 and 7. For the analysis, only pain scores on days where participants received study drug were considered. A negative change indicates a decrease in brush-evoked pain intensity from baseline.

  Baseline and day 7 (end of double blind treatment)

Secondary Outcomes (10)

• Assessment of Responder Rates

  Day 7 (end of double blind treatment)

• Onset of Current Pain Relief

  Day 1 to Day 7 (end of double blind treatment)

• Onset of Ongoing Pain Relief

  Day 1 to Day 7 (end of double blind treatment)

• Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1)

  Day -1; Day 7 (end of double blind treatment)

• Difference in Patient's Global Impression of Change

  Day 7 (end of double blind treatment)

Study Arms (3)

Matching placebo

PLACEBO COMPARATOR

Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.

Drug: Matching Placebo

GRT6010

EXPERIMENTAL

Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.

Drug: GRT6010

Pregabalin

ACTIVE COMPARATOR

Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.

Drug: Pregabalin

Interventions

GRT6010 DRUG

Oral solution given once daily.

GRT6010

Pregabalin DRUG

Over-encapsulated pregabalin capsules 75mg twice daily on Days 1 to 3, and 150mg twice daily on Days 4 to 7.

Also known as: Lyrica®

Pregabalin

Matching Placebo DRUG

Matching Placebo capsules to the over-encapsulated Pregabalin capsules and Matching Placebo oral solution to the GRT6010 solution. Capsules twice daily on Days 1 to 7. Solution once daily.

Matching placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (12)

DEU001

Mainz, D-55131, Germany

Location

DEU002

Regensburg, D-93053, Germany

Location

HUN004

Esztergom, H-2500, Hungary

Location

HUN003

Győr, H-9024, Hungary

Location

HUN001

Miskolc, H-3526, Hungary

Location

HUN008

Szikszó, H-3800, Hungary

Location

POL002

Gdansk, 80-214, Poland

Location

POL004

Lublin, 20-718, Poland

Location

POL005

Warsaw, 02-106, Poland

Location

GBR003

Belfast, BT2 7BA, United Kingdom

Location

GBR001

Glasgow, G11 6NT, United Kingdom

Location

GBR002

Manchester, M32 0UT, United Kingdom

Location

MeSH Terms

Conditions

Neuralgia

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Grünenthal GmbH

Clinical-Trials@grunenthal.com

+49 241 569 3223

Study Officials

• Director Clinical Trials

  Grünenthal GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: December 5, 2011
• Study Start: February 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: October 28, 2019
• Results First Posted: October 2, 2014

Record last verified: 2019-10

Locations

GB (3); DE (2); PL (3); HU (4)