Eslicarbazepine Acetate as Therapy in Diabetic Neuropathic Pain

• ClinicalTrials.gov Identifier: NCT01129960
• Recruitment Status: Terminated
• First Posted: May 25, 2010
• Results First Posted: July 18, 2014
• Last Update Posted: July 18, 2014
• Sponsor: Bial - Portela C S.A.
• Information provided by (Responsible Party): Bial - Portela C S.A.

Study Description

Brief Summary:

The primary objective of this study is to assess the efficacy of Eslicarbazepine acetate (ESL) as therapy in subjects with Diabetic Neuropathic Pain (DNP) over a 15 week treatment phase.

Condition or disease	Intervention/treatment	Phase
Painful Diabetic Neuropathy	Drug: Eslicarbazepine acetate (BIA 2-093); Drug: Placebo	Phase 3

Detailed Description:

Diabetic neuropathic pain (DNP) is one of the most common complications of diabetes mellitus. It currently affects about 1% of the population but its prevalence is expected to increase in coming years (European Medicines Agency 2007) in step with the increase in diabetes mellitus prevalence, which is expected to affect 220 million people by 2010

The clinical development of ESL to treat neuropathic pain is based on its chemical and pharmacodynamic relationship to sodium channel blockers, including carbamazepine, which is effective for treating some neuropathic pain conditions. Preclinical data supports the theoretical background.

This study will examine the efficacy, safety, tolerability and pharmacokinetics of Eslicarbazepine acetate for the treatment of diabetic neuropathic pain.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 332 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Double Blind, Randomized, Placebo Controlled, Parallel Group, Multicenter Clinical Study of Eslicarbazepine Acetate in Diabetic Neuropathic Pain
• Study Start Date: November 2010
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: April 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Eslicarbazepine acetate 800 mg once daily (QD)	Drug: Eslicarbazepine acetate (BIA 2-093); Tablets will be used.; Other Names: Exalief; Zebinix; BIA 2-093; ESL
Experimental: Eslicarbazepine acetate 1200 mg QD	Drug: Eslicarbazepine acetate (BIA 2-093); Tablets will be used.; Other Names: Exalief; Zebinix; BIA 2-093; ESL
Experimental: Eslicarbazepine acetate 1600 mg QD	Drug: Eslicarbazepine acetate (BIA 2-093); Tablets will be used.; Other Names: Exalief; Zebinix; BIA 2-093; ESL
Placebo Comparator: Placebo	Drug: Placebo; Tablets will be used.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Endpoint in Mean Pain [ Time Frame: baseline up to endpoint 15 weeks (3-week titration phase and 12-week treatment maintenance phase) ]
   Study was prematurely halted. The efficacy analysis was restricted to the primary efficacy variable in the interim analysis population. The intended treatment period, starting on the day of the randomization and ending at the efficacy cut-off date (31st October 2011), was the basis for the efficacy analysis; patients with less than 20 days of study medication were excluded from the analysis, except those with early discontinuation. Primary efficacy variable was the difference between the mean values of 7 daily pain scores preceding the efficacy cut-off date (endpoint mean pain score), and before randomization (baseline mean pain score), respectively. The daily pain scores were based on the morning response to the 11-point Numeric Rating Pain Scale (NRPS) question relating to average pain intensity over the last 24 hours. The NPRS is an 11-point scale from 0-10 ["0" = no pain; "10" = the most intense pain imaginable]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male and female outpatients aged 18 years or older. Female subjects are of nonchildbearing potential, defined as surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or at least 2 years postmenopausal (spontaneous amenorrhea for at least 24 months before Visit 1), or if of childbearing potential, subjects agree to use a medically acceptable nonhormonal method of contraception.
• Diagnosis of Type 1 or Type 2 diabetes mellitus.
• Pain due to bilateral peripheral polyneuropathy caused by Type 1 or Type 2 diabetes mellitus.
• Have stable glycemic control, as assessed by the investigator, and have glycosylated hemoglobin proportion of less or equal than 11% before randomization.
• A mean score between 4.0 and 9.0, inclusive, on the 24 hour average pain intensity assessment and Visit 3 (ie, 5 of 7 days, 6 of 8 days, 7 of 9 days, or 7 of 10 days).
• Compliance with patient diary completion.
• If not used to treat DNP, subjects are permitted to take nonsteroidal anti inflammatory drugs and selective serotonin reuptake inhibitors if they were kept on a stable dose for 1 month prior to Screening and are foreseen to remain stable throughout the study.
• Competent and able to freely give own informed consent.
• Female subjects of childbearing potential, who are not currently breastfeeding, must have a negative serum pregnancy test at Visit 1.

Exclusion Criteria:

• Historical exposure to drugs known to cause neuropathy.
• Significant skin lesions (active infection, ulcer, etc).
• Peripheral vascular disease with a history of amputation, except amputation of toes.
• Known intolerance to ESL or to other carboxamide derivatives (eg, carbamazepine or oxcarbazepine) or frequent or severe allergic reactions with multiple medications.
• Subjects who previously participated in a clinical study with ESL.
• Major psychiatric disorders.
• Serious or unstable disease that could compromise participation cause hospitalization during the study.
• Second or third degree atrioventricular blockade not corrected with a pacemaker or any clinically significant abnormality in the 12 lead electrocardiogram as determined by the investigator.
• Subjects taking the following drug classes and individual drugs are excluded: benzodiazepines (except short half life sleep agents), skeletal muscle relaxants, orally administered steroids, capsaicin, mexiletine, centrally acting analgesics (dextromethorphan, tramadol), opiates, topical lidocaine, anticonvulsants, tricyclic antidepressants, and serotonin norepinephrine reuptake inhibitors. These drugs require a minimum washout period of at least 5 times the half life and should be tapered appropriately using product label instructions as a guide.
• Relevant clinical laboratory abnormality that, in the investigator's opinion, can compromise the subject's safety.
• History of drug abuse or dependence (drug categories defined by DSM IV) within the past year, excluding nicotine and caffeine.
• Subjects who, in the previous 30 days, received treatment with a drug that had not received regulatory approval for any indication at the time of study entry.
• History of recurrent epileptic seizures except febrile seizures.
• History of severe gastroparesis or gastric bypass surgery.
• Neurolytic treatment for DNP.
• Injected anesthetics or steroid use within 30 days of Visit 1.
• Malignancy within past 2 years.
• History of chronic hepatitis B or C within the past 3 months or human immunodeficiency virus infection.

Contacts and Locations

Locations

Portugal

BIAL - Portela & Cª, S.A.

S. Mamede do Coronado, Portugal, 4045-457

Sponsors and Collaborators

Bial - Portela C S.A.

More Information

• Responsible Party: Bial - Portela C S.A.
• ClinicalTrials.gov Identifier: NCT01129960
• Other Study ID Numbers: BIA-2093-307; 2010-019100-23 ( EudraCT Number )
• First Posted: May 25, 2010
• Results First Posted: July 18, 2014
• Last Update Posted: July 18, 2014
• Last Verified: July 2014

Keywords provided by Bial - Portela C S.A.:

Diabetic Neuropathic Pain

Additional relevant MeSH terms:

Neuralgia; Diabetic Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Eslicarbazepine acetate; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action