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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Diabetic Peripheral Neuropathic Pain

Intervention / Treatment
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* Drug: Gabapentin/B-complex
* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gabapentin/B-complex<br> | Drug: Gabapentin/B-complex<br>* 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).<br>* Other names: Gavindo®;|
| Active Comparator: Pregabalin<br> | Drug: Pregabalin<br>* 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).<br>* Other names: Lyrica®;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gabapentin/B complex, Pregabalin, Pain, Neuropathic, Gavindo, Lyrica