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

• Leeds assessment of neuropathic symptoms and signs (LANSS) scale [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Short-Form McGill Pain Questionnaire Visual Analogue Scale (SF-MPQ VAS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  The intensity increases from "0=no pain" to "10=worst possible pain".
• Profile of Mood States (POMS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Sleep evaluation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  It will be measured how long the subject lasts to get to sleep during one week averagely.
• Patient's Global Impression of Change (PGIC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  PGIC is a subject global change assessment made by the subject experienced since start of the study in a 7-point scale where "1 = best" and "7 = worst".
• Clinical Global Impression of Change (CGIC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Assessment that physician makes about global change experienced by the subject, since the study onset, using the same 7-point scale described in the preceding paragraph for PGIC and will be obtained at the end of the study.
• Proportion of responders (subjects with at least a 30 percent and 50 percent average pain score decrease from baseline to the end of the study) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Number of subjects with Adverse Events (AEs) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

• Leeds assessment of neuropathic symptoms and signs (LANSS) scale [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Short-Form McGill Pain Questionnaire Visual Analogue Scale (SF-MPQ VAS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  The intensity increases from "0=no pain" to "10=worst possible pain"
• Profile of Mood States (POMS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Sleep evaluation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  It will be measured how long the patient lasts to get to sleep during one week averagely.
• Patient's Global Impression of Change (PGIC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  PGIC is a subject global change assessment made by the patient experienced since start of the study in a 7-point scale where "1 = best" and "7 = worst"
• Clinical Global Impression of Change (CGIC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Assessment that physician makes about global change experienced by the subject since the study onset, using the same 7-point scale described in the preceding paragraph for PGIC and obtained at the end of the study.
• Proportion of responders (patients with at least a 30% and 50% average pain score decrease from baseline to the end of the study) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Number of Patients with Adverse Events (AEs) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

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 management.

Primary Objective:

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

Secondary Objectives:

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

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

The treatment duration by subject is 12 weeks.

• Drug: Gavindo®
  Gabapentin/B Complex (Gavindo®)
  Other Name: Gavindo®
• Drug: Pregabalin
  Pregabalin (Lyrica®)
  Other Name: Lyrica®

• Experimental: Gabapentin/B Complex

  The initial dose of Gabapentin/B Complex (Gavindo®) will be 300 milligram per day (mg/day) (Day 1), 600 mg/day (Day 2, divided every 12 hours [hrs]), 900 mg/day (Day 3, divided every 8 hrs according to dose algorithm:

  Visit 1: 900 mg/day (1 tablet, every 8 hrs). Visit 2: 1,800 mg/day (2 tablets, every 8 hrs). Visit 3: 2,700 mg/day (3 tablets, every 8 hrs). Visits 4 and 5: 3,600 mg/day. The maximum permitted dose is 3.600 mg/day.

  Subjects treated during follow-up period of the study with this drug, are Group A arm. At each visit, drug with exact number of doses to the subject (exact dose for the next visit) will be provided.

  If subject, adjusting Gavindo® dose could suffer any discomfort or adverse event, subject shall notify immediately to Principal Investigator.

  If the subject does not present a good tolerability, subject could come back to the previous doses.

  Intervention: Drug: Gavindo®
• Active Comparator: Pregabalin

  The initial dose of Pregabalin (Lyrica®) will be 150 mg/day (1 capsule, with 75 milligram [mg] every 12 hrs) during the first 7 days of treatment. Subsequently it will be adjusted according to dosing algorithm:

  Visit 1: 300 mg/day (1 capsule, with 150 mg every 12 hrs). Visits 2 to 5: 600 mg/day (2 capsules, with 150 mg every 12 hrs). The maximum permitted dose is 600 mg/day. Subjects treated during the follow-up study with this drug, are the Group B arm.

  If subject, adjusting Lyrica® dose could suffer any discomfort or adverse event, he shall notify immediately to Principal Investigator.

  Intervention: Drug: Pregabalin

Inclusion Criteria:

• Subjects with mild to moderate DPN diagnosed by Leeds assessment of neuropathic symptoms and signs (LANSS) scale of greater than or equal to 1 year of development and less than 5 years from diagnosis, hypoglycemic therapy (greater than or equal to 6 weeks) and stable condition (glycosylated hemoglobin [HbA1c] less than or equal to 10 percent in Screening visit)
• Male or female
• Age 18 to 70 years
• Written informed consent (IC)
• Diabetes mellitus (DM) Type 1 or 2
• Pain caused by mild to moderate sensory and motor DPN greater than or equal to 1 year of development and 5 years from diagnosis
• Subjects with a 2:40 millimeter (mm) in SF-MPQ VAS on Screening and Baseline visits, and complete daily NPIS (a minimum of four days) during week prior to randomization and with a daily average minimum NPIS pain score of 4 for 7 days prior to randomization (with a washout period) and Leeds assessment of neuropathic symptoms and signs (LANSS) scale
• Normal chest radiography (Chest TI)
• Hypoglycemic therapy stable for at least six weeks before randomization
• HbA1c=10 percent on Screening visit
• Non-pregnant women and no plans for pregnancy during study period
• With or without pain medication stable for at least 4 weeks in which there is no acceptable pain relief, the latter with the corresponding washing period
• Women of childbearing age must submit a negative pregnancy test before treatment randomization, and should use adequate contraception and medically accepted throughout the study period
• Other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Suicide risk, defined by a 2 or more score in Beck Depression Scale (BDI) Question 9
• New York Heart Association (NYHA) Class III or IV congestive heart failure
• Subjects with severe or unstable cardiovascular disease, hepatic, renal, respiratory, hematological disorders, problems with peripheral vascular disease or other medical or psychiatric conditions that could jeopardize their participation or likely to lead to hospitalization during the course of the study
• Any condition that could confound the assessment of painful DPN, especially amputations of the fingers, is not, neurological disorders and non-diabetic skin conditions that affect the limbs painful sensation
• Subjects will be specifically excluded if they have a calculated Baseline less than 60 milliliter per minute (mL/min). Creatinine clearance, whether baseline leukocyte count is less than 2,500 per cubic millimeter (/mm^3), neutrophil count less than 1,500/mm^3 or platelet count less than 100 * 10^3 cubic millimeter (mm^3)
• Subjects who have previously participated in another clinical trial with pregabalin and/or gabapentin or gabapentin/B complex in the 30 days prior to Screening
• Subjects with encephalopathy by ammonium or urea cycle disorders (UCD)
• Subjects with uncontrolled narrow angle glaucoma
• Presence of a disorder and/or anticonvulsant therapy
• Nursing women or within three months postpartum
• Morbid obesity (body mass index, 2:40)
• HbA1c greater than 10 percent
• Major surgery within three months prior to randomization
• Any surgery 2 weeks prior randomization or within study period must be approved by the Sponsor or designee
• Blood donation within 60 days before randomization
• Alcohol dependence or abuse, narcotics, opiates, or other addictive substances, as well as energy drinks
• Hypersensitivity history to study drugs or drugs with similar chemical structures
• Unreliability historical or suspicion, poor cooperation or non-compliance with medical treatments
• Subjects with arthritis, sciatica, fibromyalgia, restless leg syndrome, no neuropathic musculoskeletal pain or chronic back pain
• Other protocol-defined exclusion criteria may apply