Painful Diabetic Neuropathy
Conditions
Keywords
Analgesia, Diabetic Neuropathy, Neuropathic pain, Painful, Chronic pain
Brief summary
This trial is assessing the analgesic efficacy and safety of a new central analgesic in subjects with pain due to diabetic peripheral neuropathy (DPN).
Interventions
DRUGGRT3938Y
Overencapsulated tablets of GRT3983Y, 100 to 300mg daily dose, 16 weeks treatment.
DRUGPlacebo
Overencapsulated tablets of placebo, 16 weeks treatment.
Sponsors
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Symmetrical painful diabetic peripheral neuropathy
Exclusion criteria
* History of hypersensitivity, allergy or contraindication to opioids and acetaminophen * Confounding painful conditions * Significant vascular disease * History or risk of seizure * Chronic disease that might effect drug absorption, distribution, metabolism, or excretion * Female subjects who are being pregnant or breastfeeding * Evidence or history of alcohol, medication, or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Intensity | Baseline; last 7 days of 12-week maintenance | The primary efficacy endpoint is the change from baseline in the mean of the daily average pain intensity scores (on an 11-point NRS) over the last 7 days of the 12-week maintenance (Week 16). |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Subjects Achieving Various Levels of Pain Improvement (Including 30% and 50%) Based on the Percent Change From Baseline to the Last 7 Days of the 12-week Maintenance on an 11-point NRS (Responder Analysis). | Baseline, Last 7 days of 12-week maintenance |
| Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over Each Week of Maintenance. | Baseline; daily scores over each week of maintenance |
| Change From Baseline of the Weekly Mean of Night Pain Intensity (on an 11-point NRS). | Baseline; weekly mean |
| Change From Baseline of the Weekly Mean of Current Pain Intensity (on an 11-point NRS) in the Evening and in the Morning, Respectively. | Baseline, weekly mean |
| Brief Pain Inventory Scores: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, and Day 113 (Final Visit). | Baseline, weekly mean |
| Neuropathic Pain Symptoms Inventory: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99 and Day 113 (Final Visit) | Baseline, weekly mean |
| Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over the Entire 12-week Maintenance | Baseline, Daily scores over entire 12 week maintenance |
| Short Form 36 Health Survey (SF-36®): Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). | Baseline, Day 29, Day 71 and Day 113. |
| EuroQol-5 Dimension Health Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). | Baseline, Day 29, Day 71 and Day 113. |
| Assessment of Each Item of the Leeds Sleep Evaluation Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). | Baseline, Day 29, Day 71 and Day 113. |
| Hospital Anxiety and Depression Scale: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). | Baseline, Day 29, Day 71 and Day 113. |
| Time to Treatment Discontinuation Due to Lack of Efficacy. | Baseline to time to treatment discontinuation |
| Assessment of Rescue Medication Usage During the 4-week Titration. | 4-week titration phase |
| Patient Global Impression of Change Using a 7-point Verbal Rating Scale, on Day 29, Day 71 and Day 113 (Final Visit). | Day 29, Day 71 and Day 113. |
Countries
United States
Participant flow
Pre-assignment details
503 participants were excluded from the trial before assignment to a treatment group because they did not meet the inclusion and or exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| GRT3983Y | 27 |
| Placebo | 23 |
| Total | 50 |
Baseline characteristics
| Characteristic | GRT3983Y | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 16 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 34 Participants | 14 Participants |
| Age, Continuous | 59.38 years STANDARD_DEVIATION 8.942 | 59.79 years STANDARD_DEVIATION 9.568 | 60.27 years STANDARD_DEVIATION 10.438 |
| Region of Enrollment United States | 27 participants | 50 participants | 23 participants |
| Sex: Female, Male Female | 12 Participants | 20 Participants | 8 Participants |
| Sex: Female, Male Male | 15 Participants | 30 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 27 | 14 / 23 |
| serious Total, serious adverse events | 2 / 27 | 1 / 23 |
Outcome results
Primary
Average Pain Intensity
The primary efficacy endpoint is the change from baseline in the mean of the daily average pain intensity scores (on an 11-point NRS) over the last 7 days of the 12-week maintenance (Week 16).
Time frame: Baseline; last 7 days of 12-week maintenance
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Assessment of Each Item of the Leeds Sleep Evaluation Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time frame: Baseline, Day 29, Day 71 and Day 113.
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Assessment of Rescue Medication Usage During the 4-week Titration.
Time frame: 4-week titration phase
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Brief Pain Inventory Scores: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, and Day 113 (Final Visit).
Time frame: Baseline, weekly mean
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over Each Week of Maintenance.
Time frame: Baseline; daily scores over each week of maintenance
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over the Entire 12-week Maintenance
Time frame: Baseline, Daily scores over entire 12 week maintenance
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Change From Baseline of the Weekly Mean of Current Pain Intensity (on an 11-point NRS) in the Evening and in the Morning, Respectively.
Time frame: Baseline, weekly mean
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Change From Baseline of the Weekly Mean of Night Pain Intensity (on an 11-point NRS).
Time frame: Baseline; weekly mean
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
EuroQol-5 Dimension Health Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time frame: Baseline, Day 29, Day 71 and Day 113.
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Hospital Anxiety and Depression Scale: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time frame: Baseline, Day 29, Day 71 and Day 113.
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Neuropathic Pain Symptoms Inventory: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99 and Day 113 (Final Visit)
Time frame: Baseline, weekly mean
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Patient Global Impression of Change Using a 7-point Verbal Rating Scale, on Day 29, Day 71 and Day 113 (Final Visit).
Time frame: Day 29, Day 71 and Day 113.
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Proportion of Subjects Achieving Various Levels of Pain Improvement (Including 30% and 50%) Based on the Percent Change From Baseline to the Last 7 Days of the 12-week Maintenance on an 11-point NRS (Responder Analysis).
Time frame: Baseline, Last 7 days of 12-week maintenance
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Short Form 36 Health Survey (SF-36®): Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time frame: Baseline, Day 29, Day 71 and Day 113.
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.
Secondary
Time to Treatment Discontinuation Due to Lack of Efficacy.
Time frame: Baseline to time to treatment discontinuation
Population: Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.