Efficacy and Safety of Gabapentin/B-complex Versus Pregabalin in Diabetic Peripheral Neuropathy Pain Management

Multicenter, Randomized, Open-label, Parallel Group, Phase IV Study to Compare the Efficacy and Safety of Gabapentin/B-complex Versus Pregabalin in the Management of Diabetic Peripheral Neuropathic Pain

This is a multicenter, randomized, open-label, parallel, Phase 4 clinical trial to compare efficacy and safety of gabapentin/B-complex versus pregabalin in diabetic peripheral neuropathy pain (DPNP) management.

Study Overview

• Status: Completed
• Conditions: Diabetic Peripheral Neuropathic Pain
• Intervention / Treatment: Drug: Gabapentin/B-complex; Drug: Pregabalin

Detailed Description

Primary Objective:

To compare the efficacy of gabapentin/B-complex versus pregabalin administered for 12 weeks in the treatment of pain in mild to moderate diabetic peripheral neuropathy (DPN) of acute or chronic presentation.

Secondary Objectives:

To determine the safety and tolerability of gabapentin/B-complex versus pregabalin administered for 12 weeks in the treatment of pain in mild to moderate DPN of acute or chronic presentation.

Subjects will be randomized in a 1:1 ratio to receive gabapentin/B-complex or pregabalin.

The duration of treatment per subject will be 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Females or males undististincally
• Age 18 to 70 years
• Signed informed consent (IC) by the subject
• Diabetes mellitus (DM) Type 1 or 2
• Pain due to sensorial or motor DPN of low to moderate intensity, greater than or equal to (>=) 1 year of evolution and less than or equal to (=<)5 years of being diagnosed
• Subjects who score >=40 millimeter (mm) in the visual analogue scale (VAS) of the McGill pain questionnaire (MPQ) at selection and Baseline visit, and who complete on a daily basis the numeric pain intensity (NPI) (at least 4 days a week) during the week previous to randomization and whose daily mean score is of at least 4, during the 7 days previous to randomization (with a wash-out period)
• Normal chest radiography
• Stable hypoglycemic treatment, at least 6 weeks before randomization
• Glycosylated hemoglobin (HbA1c) =<10 percent at selection visit
• Women must not be pregnant and must not have pregnancy plans during the period of the study duration
• Subjects not medicated or under analgesic stable medication during a minimum of 4 weeks, where no acceptable relief of pain is achieved; in the last case, with the corresponding wash-out period
• Women of childbearing age must submit a negative pregnancy test before treatment randomization and should use a contraceptive method medically accepted, during the study period

Exclusion Criteria:

• Suicide risk defined as a score of 2 or higher, in question 9 of the beck depression test
• Congestive heart failure Class III or IV of the New York Heart Association (NYHA)
• Subjects with serious or unstable coronary heart disease, hepatic, kidney, respiratory, hematological alterations, problems with peripheral vascular disease, or other medical or psychiatric conditions that can put in risk the participation of the subject in the study or that may lead to hospitalization during the study period
• Any condition that may lead to confusion of the diagnostic of painful DPN, in particular amputations -other than fingers/toes-, not diabetic neurological disorder and skin conditions that may affect sensation at the painful limbs
• Subjects with Baseline calculated creatinine clearance less than (<) 60 milliliter per minute (mL/min), Baseline leukocyte count < 2,500 per cubic millimeter (/mm^3), Baseline neutrophils count < 1,500/mm^3 or platelets < 100 * 10^3 /mm^3
• Subjects who have participated previously in some other study of pregabalin or gabapentin or gabapentin/B-complex, during 30 days previous to selection
• Subjects with encephalopathy caused by ammonia with alterations in the cycle of urea
• Subjects with uncontrolled closed-angle glaucoma
• Subject with presence of a disorder or an anticonvulsant treatment
• Breastfeeding women or during the first 3 months postpartum
• Morbid obesity (body mass index [BMI] >=40)
• Glycosylated hemoglobin (HbA1c) greater than (>) 10 percent
• Major surgery 3 months previous to randomization
• Any surgery 2 weeks previous to randomization process, or programmed during the study period should have been authorized by the Sponsor or appointed representative
• Blood donors 60 days previous to randomization
• Abuse or dependency of alcohol, narcotics, opioids or any other addictive substances, or energizing drinks
• History of hypersensitivity to the drugs in the study or drugs with similar chemical structures
• History or suspicion of lack of trust, poor cooperation of lack of compliance of medical treatments
• Subjects with arthritis, sciatic, fibromyalgia, restless leg syndrome, non-neuropathic muscle-skeletal pain or back chronic pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pregabalin	Drug: Pregabalin; Pregabalin (Lyrica®) capsule will be administered orally at an initial dose of 150 mg/day (one 75 mg capsule every 12-hour) from Day 1 to 7, followed by 300 mg/day (one 150 mg capsule every 12-hour) on Day 7, then 600 mg/day (two 150 mg capsule every 12-hour) on Days 21, 35, 56 and 84. Maximum dose allowed will be 600 mg/day. The total duration of treatment will be 84 days (12 weeks).; Other Names: Lyrica®
Experimental: Gabapentin/B-complex	Drug: Gabapentin/B-complex; Gabapentin/B-complex (Gavindo®) tablet will be administered orally at an initial dose of 300 milligram per day (mg/day) on Day 1, followed by 600 mg/day (one 300 milligram [mg] tablet every 12-hour) on Day 2, then 900 mg/day (one 300 mg tablet every 8-hour) on Day 7, then 1800 mg/day (two 300 mg tablets every 8-hour) on Day 21, then 2700 mg/day (three 300 mg tablets every 8-hour) on Day 35, and finally 3600 mg/day (four 300 mg tablets every 8-hour) on Days 56 and 84. Maximum dose allowed will be 3600 mg/day. The total duration of treatment will be 84 days (12 weeks).; Other Names: Gavindo®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Average Numeric Pain Intensity Scale (NPIS) Score at Day 84	An average NPIS pain score (daily average records of the past seven days) was evaluated. Numeric pain intensity scale (NPIS) is a 11-point scale, with 0 representing no pain and 10 representing the worst possible pain. The participants were asked to mark the number that best represents the current level of pain they have experienced during the previous 24 hours. Change from baseline data has been calculated as value at baseline minus value at Day 84.	Baseline and Day 84 (Week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Scale Score at Day 84	The LANSS scale score is 7-item pain scale that consists of grouped sensory description and sensory examination with simple scoring system. Evaluations in two main areas: pain and sensorial exploration. The first 5 questions asks for presence of unpleasant skin sensations (pricking, tingling, pins and needles), appearance of skin (mottled, red, or pink), increased sensitivity of skin to touch, sudden bursts of electric shock sensations, and hot or burning skin sensations. Last 2 questions involve sensory testing for the presence of allodynia and altered pinprick threshold. Different numbers of points, relative to their significance to neuropathic pain, are given to positive answers for maximum of 24 points. A score less than 12 makes unlikely that participant's symptoms are neuropathic in nature, whereas score more than 12 make neuropathic mechanisms likely to be contributing to participant's pain. Change from baseline data has been calculated as value at baseline minus value at Day 84.	Baseline and Day 84 (Week 12)
Change From Baseline in Visual Analogue Scale (VAS) Score at Day 84	VAS is used to rate the pain as per 10 centimeter (cm) line. The pain intensity score ranges from '0=no pain' to '10=worst possible pain'. Change from baseline data has been calculated as value at baseline minus value at Day 84.	Baseline and Day 84 (Week 12)
Profile of Mood States (POMS) Score	POMS is a rating scale, which comprises of 65 items that are evaluated in a 0-4 scale, where 0 means "not at all" and 4 "extremely". The scores for the 65 items are added in various combinations to throw six validated factors which are used to calculate total POMS score: (tension-anxiety) + (depression-dejection) + (anger-hostility)+ (fatigue-Inertia) + (confusion-bewilderment) - (vigor-activity). Score range (-40 to 192). Score -40 denotes the best score and score 192 denotes the worst score.	Day 84 (Week 12)
Sleep Evaluation: Number of Participants Who Fell Asleep in Pre-specified Time Duration	Sleep evaluation was performed by assessing number of participants who fell asleep in a particular pre-specified range of time duration, that is, 0-15 minutes, 16-30 minutes, 31-45 minutes, 46-60 minutes and greater than 60 minutes at Day 84 (Week 12).	Day 84 (Week 12)
Number of Participants With Various Health Conditions Based on Global Impression of Patient Change (GIPC) Scale	GIPC is an assessment that the participant's global change in health condition from start of the study on a 7-point scale (1 = extremely improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse 6 = much worse, 7 = extremely worse).	Baseline and Day 84 (Week 12)
Number of Participants With Various Health Conditions Based on Clinical Global Impression of Change (CGIC) Scale	CGIC is an assessment that the physician performs to assess the participant's global change in health condition from start of the study on a 7-point scale (1 = extremely improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse 6 = much worse, 7 = extremely worse).	Baseline and Day 84 (Week 12)
Percentage of Participants With at Least 30 and 50 Percent (%) Improvement in Numeric Pain Intensity Scale (NPIS) From Baseline at Day 84 (Week 12)	NPIS is a 11-point scale, with 0 representing no pain and 10 representing the worst possible pain. The participants were asked to mark the number that best represents the current level of pain they have experienced during the previous 24 hours.	Baseline and Day 84 (Week 12)
Number of Participants With Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.	Day 7 up to Day 84 (+7 days)

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: Merck S.A. de C.V., Mexico
• Investigators: Study Director: Clinical Research Manager, Merck S.A de C.V, Mexiko, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Mimenza Alvarado A, Aguilar Navarro S. Clinical Trial Assessing the Efficacy of Gabapentin Plus B Complex (B1/B12) versus Pregabalin for Treating Painful Diabetic Neuropathy. J Diabetes Res. 2016;2016:4078695. doi: 10.1155/2016/4078695. Epub 2016 Jan 17.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Estimate): February 6, 2014
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Pain; Pregabalin; Lyrica; Neuropathic; Gabapentin/B complex; Gavindo
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Gabapentin; Pregabalin
• Other Study ID Numbers: EMR200054-603 CL028