Diabetic Neuropathies, Polyneuropathies
Conditions
Keywords
Polyneuropathy, Diabetes Mellitus, Diabetic peripheral neuropathy
Brief summary
This is a prospective, randomized, double blind, comparative, experimental controlled Phase 3 clinical trial to assess the efficacy, safety and superiority of F0343 (gabapentin combined with B vitamins) compared to gabapentin alone for treating neuropathic pain in subjects with chronic distal diabetic polyneuropathy.
Detailed description
Subjects will be assigned to one of the two arms of the study, after having been deemed eligible during the screening visit in random double-blind design. Subjects will be evaluated for a 4 week period. OBJECTIVES * To assess the effects of F0434 and gabapentin alone on neuropathic pain and Quality Of Life (QOL) of subjects with diabetic neuropathy through a current and validated neuropathic pain scale along with the QOL questionnaire.
Interventions
DRUGF0434
F0434 will be administered orally with an initial dosage of 3 capsules per day divided into 3 doses with a time interval of 8 hours between each dose. The subject will continue with this dosage for one week and afterwards, the initial dosage will be increased from 3 capsules per day divided into 3 doses with the same time interval between doses, until visit 3 (week 2).
DRUGGabapentin
Gabapentin will be administered orally with an initial dosage of 3 capsules per day divided into 3 doses with a time interval of 8 hours between each dose. The subject will continue with this dosage for one week and afterwards, the initial dosage will be increased from 3 capsules per day divided into 3 doses with the same time interval between doses, until visit 3 (week 2)
Sponsors
Merck S.A. de C.V., Mexico
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subjects diagnosed with diabetes mellitus type 2 * Subjects with a history of neuropathic pain in the last 3 Months * Men and women in reproductive age with a family planning method * Subjects aged between 18 to 70 years * Subjects with glycosylated haemoglobin (HbA1c) greater than 7% and less than 15% * Subjects that obtain a grade equal or greater than 4 in the visual analogue scale during the screening visit
Exclusion criteria
* Subjects diagnosed as being pregnant or in state of lactation * Subjects with serum creatinine greater than 1.2 or creatinine depuration in 24 hour urine, less than 60mL/min * Subjects who are receiving treatment with anti-depressants, anti-epileptics, and are taking vitamin B1 and B12 for treatment of neuropathic diabetes * Subjects who are being pharmacologically treated for epilepsy * Subjects diagnosed with rheumatic and hepatic disease and diagnosed with neuropathy for other causes * Subjects with psychological and psychiatric alteration that hinders adequate collaboration in the study * Subjects with any orthopaedic alteration of any extremity * Subjects with peripheral artery disease * Subjects taking more than two neuropathic pain medicines * Subjects with history of alcohol, cocaine, marijuana or benzodiazepine substance abuse * Subjects with acid-peptic disease * Subjects with history of neoplasm of any type
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Neuropathic Pain Score at Visit 3 (Week 1) | Visit 3 (Week 1) | Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain. |
| Mean Neuropathic Pain Score at Visit 4 (Week 2) | Visit 4 (Week 2) | Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain. |
| Mean Neuropathic Pain Score at Visit 5 (Week 3) | Visit 5 (Week 3) | Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain. |
| Mean Neuropathic Pain Score at Visit 6 (Week 4) | Visit 6 (Week 4) | Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Visit 2 (Baseline) to Visit 6 (Week 4) | SF-36 is a standardized health survey consisting of 36 questions to measure functional health status. Summary scores are calculated using the following 8 dimensions: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is obtained by SF-36 algorithm and it is represented as an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). Higher scores are indicative of a better health status. |
Countries
Mexico
Participant flow
Pre-assignment details
A total of 104 participants were recruited for the study, out of which 29 participants were screen failures which were not randomized and did not receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin Gabapentin 300 mg capsule was taken orally with an initial dosage of 3 capsules per day divided into 3 doses with a time interval of 8 hours between each dose for one week; and then dose increased up to 3 weeks as per dosage adjustment schedule. | 38 |
| MF0434 + Gabapentin MF0434 and Gabapentin 300 mg capsule was taken orally with an initial dosage of 3 capsules per day divided into 3 doses with a time interval of 8 hours between each dose for one week and then dose increased up to 3 weeks as per dosage adjustment schedule. | 37 |
| Total | 75 |
Baseline characteristics
| Characteristic | Gabapentin | MF0434 + Gabapentin | Total |
|---|---|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 9.7 | 51.1 years STANDARD_DEVIATION 9.9 | 51.9 years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 19 Participants | 21 Participants | 40 Participants |
| Sex: Female, Male Male | 19 Participants | 16 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 38 | 23 / 37 |
| serious Total, serious adverse events | 0 / 38 | 0 / 37 |
Outcome results
Primary
Mean Neuropathic Pain Score at Visit 3 (Week 1)
Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain.
Time frame: Visit 3 (Week 1)
Population: Per Protocol (PP) population included all participants who were randomized and took at least 1 dose of study medication. In this clinical study Intention to treat (ITT) and PP populations were the same.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Mean Neuropathic Pain Score at Visit 3 (Week 1) | 51.00 Units on a Scale | Standard Deviation 17.39 |
| MF0434 + Gabapentin | Mean Neuropathic Pain Score at Visit 3 (Week 1) | 50.70 Units on a Scale | Standard Deviation 16.67 |
Primary
Mean Neuropathic Pain Score at Visit 4 (Week 2)
Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain.
Time frame: Visit 4 (Week 2)
Population: PP population included all participants who were randomized and took at least 1 dose of study medication. In this clinical study ITT and PP populations were the same.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Mean Neuropathic Pain Score at Visit 4 (Week 2) | 41.24 Units on a Scale | Standard Deviation 16.21 |
| MF0434 + Gabapentin | Mean Neuropathic Pain Score at Visit 4 (Week 2) | 36.94 Units on a Scale | Standard Deviation 15.05 |
Primary
Mean Neuropathic Pain Score at Visit 5 (Week 3)
Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain.
Time frame: Visit 5 (Week 3)
Population: PP population included all participants who were randomized and took at least 1 dose of study medication. In this clinical study ITT and PP populations were the same.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Mean Neuropathic Pain Score at Visit 5 (Week 3) | 33.74 Units on a Scale | Standard Deviation 19.54 |
| MF0434 + Gabapentin | Mean Neuropathic Pain Score at Visit 5 (Week 3) | 24.86 Units on a Scale | Standard Deviation 13.52 |
Primary
Mean Neuropathic Pain Score at Visit 6 (Week 4)
Neuropathic pain score included 10 pain descriptors (intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial and unpleasant) quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable). Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain.
Time frame: Visit 6 (Week 4)
Population: PP population included all participants who were randomized and took at least 1 dose of study medication. In this clinical study ITT and PP populations were the same.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Mean Neuropathic Pain Score at Visit 6 (Week 4) | 22.08 Units on a Scale | Standard Deviation 18.54 |
| MF0434 + Gabapentin | Mean Neuropathic Pain Score at Visit 6 (Week 4) | 17.29 Units on a Scale | Standard Deviation 15.53 |
Secondary
Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire
SF-36 is a standardized health survey consisting of 36 questions to measure functional health status. Summary scores are calculated using the following 8 dimensions: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The score for a component is obtained by SF-36 algorithm and it is represented as an average of the individual question scores, which are scaled 0 (not functioning) to 100 (highest functioning). Higher scores are indicative of a better health status.
Time frame: Visit 2 (Baseline) to Visit 6 (Week 4)
Population: PP population included all participants who were randomized and took at least 1 dose of study medication. In this clinical study ITT and PP populations were the same. Two participants in the MF0434 + Gabapentin group had missing values and hence are not included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 1 (Visit 3): General SF-36 QoL Index | 65.779 Units on a Scale | Standard Deviation 20.882 |
| Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 3 (Visit 5): General SF-36 QoL Index | 73.058 Units on a Scale | Standard Deviation 18.102 |
| Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 2 (Visit 4): General SF-36 QoL Index | 69.531 Units on a Scale | Standard Deviation 18.987 |
| Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 4 (Visit 6): General SF-36 QoL Index | 78.869 Units on a Scale | Standard Deviation 17.01 |
| Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Baseline (Visit 2): General SF-36 QoL Index | 53.044 Units on a Scale | Standard Deviation 22.409 |
| MF0434 + Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 4 (Visit 6): General SF-36 QoL Index | 82.331 Units on a Scale | Standard Deviation 15.793 |
| MF0434 + Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Baseline (Visit 2): General SF-36 QoL Index | 56.507 Units on a Scale | Standard Deviation 19.523 |
| MF0434 + Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 1 (Visit 3): General SF-36 QoL Index | 65.610 Units on a Scale | Standard Deviation 18.599 |
| MF0434 + Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 2 (Visit 4): General SF-36 QoL Index | 74.370 Units on a Scale | Standard Deviation 15.595 |
| MF0434 + Gabapentin | Quality of Life Survey Assessed Using Short Form 36 (SF-36) Questionnaire | Week 3 (Visit 5): General SF-36 QoL Index | 78.075 Units on a Scale | Standard Deviation 15.819 |