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

Sponsor
Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Completed
CT.gov ID
NCT01364298
Collaborator
Merck S.A. de C.V., Mexico (Industry)
353
1
2
15
23.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
353 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Jul 1, 2012
Actual Study Completion Date :
Jul 1, 2012

Arms and Interventions

Arm Intervention/Treatment
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®
  • 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®
  • Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Average Numeric Pain Intensity Scale (NPIS) Score at Day 84 [Baseline and Day 84 (Week 12)]

      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.

    Secondary Outcome Measures

    1. Change From Baseline in Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Scale Score at Day 84 [Baseline and Day 84 (Week 12)]

      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.

    2. Change From Baseline in Visual Analogue Scale (VAS) Score at Day 84 [Baseline and Day 84 (Week 12)]

      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.

    3. Profile of Mood States (POMS) Score [Day 84 (Week 12)]

      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.

    4. Sleep Evaluation: Number of Participants Who Fell Asleep in Pre-specified Time Duration [Day 84 (Week 12)]

      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).

    5. Number of Participants With Various Health Conditions Based on Global Impression of Patient Change (GIPC) Scale [Baseline and Day 84 (Week 12)]

      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).

    6. Number of Participants With Various Health Conditions Based on Clinical Global Impression of Change (CGIC) Scale [Baseline and Day 84 (Week 12)]

      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).

    7. Percentage of Participants With at Least 30 and 50 Percent (%) Improvement in Numeric Pain Intensity Scale (NPIS) From Baseline at Day 84 (Week 12) [Baseline and 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.

    8. Number of Participants With Adverse Events (AEs) [Day 7 up to Day 84 (+7 days)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 (/mm3), Baseline neutrophils count < 1,500/mm3 or platelets < 100 * 103 /mm3

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Mexico City Mexico

    Sponsors and Collaborators

    • Merck KGaA, Darmstadt, Germany
    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck KGaA, Darmstadt, Germany
    ClinicalTrials.gov Identifier:
    NCT01364298
    Other Study ID Numbers:
    • EMR200054-603 CL028
    First Posted:
    Jun 2, 2011
    Last Update Posted:
    Feb 6, 2014
    Last Verified:
    Dec 1, 2013
    Keywords provided by Merck KGaA, Darmstadt, Germany
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Period Title: Overall Study
    STARTED 176 177
    Treated 174 174
    COMPLETED 162 154
    NOT COMPLETED 14 23

    Baseline Characteristics

    Arm/Group Title Gabapentin/B-complex Pregabalin Total
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks). Total of all reporting groups
    Overall Participants 174 174 348
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53.2
    (10.5)
    54.3
    (9.4)
    53.8
    (9.9)
    Sex: Female, Male (Count of Participants)
    Female
    119
    68.4%
    109
    62.6%
    228
    65.5%
    Male
    55
    31.6%
    65
    37.4%
    120
    34.5%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Average Numeric Pain Intensity Scale (NPIS) Score at Day 84
    Description 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.
    Time Frame Baseline and Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug. 'n' signifies number of participants who were evaluable for specified categories at different time points.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 147 123
    Baseline (n=147, 123)
    6.7
    (1.5)
    6.8
    (1.4)
    Change at Day 84 (n=146, 122)
    3.905
    (2.639)
    4.260
    (2.329)
    2. Secondary Outcome
    Title Change From Baseline in Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Scale Score at Day 84
    Description 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.
    Time Frame Baseline and Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug. 'n' signifies number of participants who were evaluable for specified categories at different time points.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 147 123
    Baseline (n=147, 123)
    16.2
    (3.6)
    15.8
    (4.0)
    Change at Day 84 (n=146, 122)
    8.082
    (7.470)
    6.967
    (6.839)
    3. Secondary Outcome
    Title Change From Baseline in Visual Analogue Scale (VAS) Score at Day 84
    Description 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.
    Time Frame Baseline and Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug. 'n' signifies number of participants who were evaluable for specified categories at different time points.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 147 123
    Baseline (n=147, 123)
    7.0
    (1.8)
    7.1
    (1.5)
    Change at Day 84 (n=146, 122)
    4.182
    (2.890)
    4.529
    (2.382)
    4. Secondary Outcome
    Title Profile of Mood States (POMS) Score
    Description 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.
    Time Frame Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 147 123
    Mean (Standard Deviation) [units on a scale]
    1.3
    (26.1)
    3.4
    (25.5)
    5. Secondary Outcome
    Title Sleep Evaluation: Number of Participants Who Fell Asleep in Pre-specified Time Duration
    Description 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).
    Time Frame Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 147 123
    0 to 15 minutes
    85
    (6.2) 48.9%
    72
    (5.4) 41.4%
    16 to 30 minutes
    33
    (2.8) 19%
    33
    (2.9) 19%
    31 to 45 minutes
    13
    7.5%
    12
    6.9%
    46 to 60 minutes
    8
    4.6%
    4
    2.3%
    Greater than 60 minutes
    8
    4.6%
    2
    1.1%
    6. Secondary Outcome
    Title Number of Participants With Various Health Conditions Based on Global Impression of Patient Change (GIPC) Scale
    Description 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).
    Time Frame Baseline and Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 145 122
    Health: extremely improved
    62
    35.6%
    47
    27%
    Health: much improved
    73
    42%
    65
    37.4%
    Health: minimally improved
    10
    5.7%
    10
    5.7%
    7. Secondary Outcome
    Title Number of Participants With Various Health Conditions Based on Clinical Global Impression of Change (CGIC) Scale
    Description 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).
    Time Frame Baseline and Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 145 122
    Health: extremely improved
    55
    31.6%
    47
    27%
    Health: much improved
    79
    45.4%
    69
    39.7%
    Health: minimally improved
    11
    6.3%
    6
    3.4%
    8. Secondary Outcome
    Title Percentage of Participants With at Least 30 and 50 Percent (%) Improvement in Numeric Pain Intensity Scale (NPIS) From Baseline at Day 84 (Week 12)
    Description 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.
    Time Frame Baseline and Day 84 (Week 12)

    Outcome Measure Data

    Analysis Population Description
    Per protocol population (PPP) included all the treated participants who showed no major protocol violations and were compliant with study inclusion criteria and with the proper administration of the study drug.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 147 123
    At least 30% improvement
    76.9
    44.2%
    85.4
    49.1%
    At least 50% improvement
    66.0
    37.9%
    72.4
    41.6%
    9. Secondary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description 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.
    Time Frame Day 7 up to Day 84 (+7 days)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all the randomized participants who received at least one dose of study drug.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    Measure Participants 174 174
    Number [participants]
    80
    46%
    93
    53.4%

    Adverse Events

    Time Frame Day 7 up to Day 84 (+ 7 days)
    Adverse Event Reporting Description An 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 IMP, regardless of causal relationship and even if no IMP has been administered.
    Arm/Group Title Gabapentin/B-complex Pregabalin
    Arm/Group Description Gabapentin/B-complex (Gavindo®) tablet 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 was 3600 mg/day. The total duration of treatment was 84 days (12 weeks). Pregabalin (Lyrica®) capsule 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 was 600 mg/day. The total duration of treatment was 84 days (12 weeks).
    All Cause Mortality
    Gabapentin/B-complex Pregabalin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Gabapentin/B-complex Pregabalin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/174 (0.6%) 0/174 (0%)
    Nervous system disorders
    Cerebrovascular disorder 1/174 (0.6%) 0/174 (0%)
    Other (Not Including Serious) Adverse Events
    Gabapentin/B-complex Pregabalin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 79/174 (45.4%) 93/174 (53.4%)
    Blood and lymphatic system disorders
    Anaemia 0/174 (0%) 1/174 (0.6%)
    Cardiac disorders
    Angina pectoris 1/174 (0.6%) 0/174 (0%)
    Ear and labyrinth disorders
    Tinnitus 1/174 (0.6%) 0/174 (0%)
    Hypoacusis 1/174 (0.6%) 0/174 (0%)
    Vertigo 1/174 (0.6%) 11/174 (6.3%)
    Eye disorders
    Cataract 1/174 (0.6%) 1/174 (0.6%)
    Eye irritation 0/174 (0%) 1/174 (0.6%)
    Vision blurred 0/174 (0%) 1/174 (0.6%)
    Gastrointestinal disorders
    Colitis 1/174 (0.6%) 0/174 (0%)
    Toothache 1/174 (0.6%) 0/174 (0%)
    Diarrhoea 5/174 (2.9%) 6/174 (3.4%)
    Dyspepsia 1/174 (0.6%) 0/174 (0%)
    Flatulence 1/174 (0.6%) 1/174 (0.6%)
    Gastritis 1/174 (0.6%) 2/174 (1.1%)
    Constipation 1/174 (0.6%) 0/174 (0%)
    Irritable bowel syndrome 1/174 (0.6%) 0/174 (0%)
    Nausea 1/174 (0.6%) 5/174 (2.9%)
    Vomiting 0/174 (0%) 3/174 (1.7%)
    Dry mouth 2/174 (1.1%) 0/174 (0%)
    Odynophagia 1/174 (0.6%) 0/174 (0%)
    General disorders
    Asthenia 1/174 (0.6%) 0/174 (0%)
    Gait disturbance 0/174 (0%) 6/174 (3.4%)
    Infections and infestations
    Gastroenteritis 0/174 (0%) 1/174 (0.6%)
    Respiratory tract infection 0/174 (0%) 1/174 (0.6%)
    Pharyngitis 2/174 (1.1%) 2/174 (1.1%)
    Urinary tract infection 2/174 (1.1%) 8/174 (4.6%)
    Injury, poisoning and procedural complications
    Fall 0/174 (0%) 1/174 (0.6%)
    Contusion 1/174 (0.6%) 0/174 (0%)
    Investigations
    Weight increased 1/174 (0.6%) 0/174 (0%)
    Metabolism and nutrition disorders
    Increased appetite 0/174 (0%) 1/174 (0.6%)
    Diabetes mellitus inadequate control 0/174 (0%) 1/174 (0.6%)
    Dehydration 0/174 (0%) 1/174 (0.6%)
    Hypertriglyceridemia 2/174 (1.1%) 1/174 (0.6%)
    Hypoglycaemia 1/174 (0.6%) 0/174 (0%)
    Oedema 2/174 (1.1%) 3/174 (1.7%)
    Musculoskeletal and connective tissue disorders
    Arthropathy 0/174 (0%) 1/174 (0.6%)
    Arthralgia 1/174 (0.6%) 0/174 (0%)
    Muscle spasms 1/174 (0.6%) 0/174 (0%)
    Back pain 0/174 (0%) 1/174 (0.6%)
    Pain in extremity 1/174 (0.6%) 0/174 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma 0/174 (0%) 1/174 (0.6%)
    Nervous system disorders
    Aphasia 0/174 (0%) 1/174 (0.6%)
    Movement disorder 0/174 (0%) 1/174 (0.6%)
    Headache 14/174 (8%) 13/174 (7.5%)
    Dizziness 32/174 (18.4%) 52/174 (29.9%)
    Somnolence 41/174 (23.6%) 52/174 (29.9%)
    Paraesthesia 2/174 (1.1%) 0/174 (0%)
    Speech disorder 0/174 (0%) 1/174 (0.6%)
    Psychiatric disorders
    Anxiety 0/174 (0%) 2/174 (1.1%)
    Nervousness 0/174 (0%) 1/174 (0.6%)
    Insomnia 1/174 (0.6%) 4/174 (2.3%)
    Renal and urinary disorders
    Dysuria 0/174 (0%) 1/174 (0.6%)
    Skin and subcutaneous tissue disorders
    Dermatitis 0/174 (0%) 1/174 (0.6%)
    Prurigo 1/174 (0.6%) 0/174 (0%)
    Hyperhidrosis 1/174 (0.6%) 0/174 (0%)
    Skin hyperpigmentation 1/174 (0.6%) 0/174 (0%)
    Pruritus 1/174 (0.6%) 1/174 (0.6%)
    Pityriasis 1/174 (0.6%) 0/174 (0%)
    Vascular disorders
    Vascular insufficiency 1/174 (0.6%) 0/174 (0%)
    Venous insufficiency 0/174 (0%) 1/174 (0.6%)
    Intermittent claudication 0/174 (0%) 1/174 (0.6%)
    Hypertension 1/174 (0.6%) 0/174 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Merck KGaA Communication Center
    Organization Merck Serono, a division of Merck KGaA
    Phone +49-6151-72-5200
    Email service@merckgroup.com
    Responsible Party:
    Merck KGaA, Darmstadt, Germany
    ClinicalTrials.gov Identifier:
    NCT01364298
    Other Study ID Numbers:
    • EMR200054-603 CL028
    First Posted:
    Jun 2, 2011
    Last Update Posted:
    Feb 6, 2014
    Last Verified:
    Dec 1, 2013