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(384) Evaluation of efficacy of duloxetine and pregabalin in patients with painful diabetic peripheral neuropathy
S72
The Journal of Pain
(384) Evaluation of efficacy of duloxetine and pregabalin in patients with painful diabetic peripheral neuropathy P Rahimzadeh, S Faiz, F Imani, and M Alebouyeh; Hazrat Rasul Medical Complex, Iran University of Medical Sciences, Tehran, Iran Diabetic polyneuropathy (DPNP) is a symmetrical peripheral neuropathy that results from nerve damage after prolonged periods of suboptimal glycemic control. Neuropathy is often associated with significant burning, stabbing or tingling pain and numbness, and can result in sleep interference and severe disability. The aim of this study was to compare the efficacy and safety of duloxetine (DLX), a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine, with pregabaline (PGB) a calcium Channel blocker in the management of diabetic peripheral neuropathic pain. We performed a doubleblind 12-week RCT study of patients with diabetic peripheral neuropathic pain whom have been treated with pregabaline (150 mg/d)(n=55) or doluxetine (60mg/d) (n=50)and had a daily pain score of $4 (VAS)in admission time. The primary objective was a comparison between DLX and PGB on improvement in the weekly mean of the daily pain score. Secondary efficacy measures included sleep interference score, Patient Global Impression of Change (PGIC), and Clinical Global Impression of Change (CGIC).A significant reduction in pain score (VAS), sleep interference score, PGIC, and CGIC was seen in all the two treatment groups across time with no statistically significant difference between the groups. The improvement in pain scores and sleep interference score was faster with PGB compared to DLX. (P<0.05) Adverse drug reactions were mild in 4.5% of all cases. DLX and PGB Produced a clinically and subjectively meaningful pain relief in patients with DPNP with onset of pain relief being faster with PGB.
(385) Integrated efficacy and safety of gastroretentive gabapentin in treatment of patients with postherpetic neuralgia (PHN) M Sweeney, S Panchal, S Nalamachu, D Kantor, and R Rauck; Depomed, Inc., Newark ,CA For patients with PHN, the efficacy and safety of gastroretentive gabapentin (G-GR) was established in two randomized, placebo-controlled Phase 3 studies, and confirmed in an open-label, Phase 4 study. To gain further insight into the efficacy and safety of G-GR, and in how certain variables interact, data from patients who received G-GR 1800 mg once-daily in these studies were integrated and are being analyzed. The integrated dataset includes 546 patients in the efficacy population and 556 in the safety population. Efficacy evaluations in the dataset include Visual Analog Scale (VAS) and Brief Pain Inventory (BPI) completed at baseline and end of study (Week 10 for Phase 3, Week 8 for Phase 4), and Patients’/Clinical Global Impression of Change (P/CGIC) completed at end of study. Preliminary efficacy results have demonstrated a consistent, statistically significant reduction in VAS score by end of study. Further analyses will explore relationships between reduction in pain, improvements in quality of life, and baseline patient and disease characteristics. In addition, we will ascertain whether any factors are predictive of reductions in pain and improvements in quality of life.The integrated safety data show that G-GR was generally well tolerated. Seventy-two (12.9%) patients discontinued due to adverse events (AEs). The incidence of AEs decreased rapidly from 21% to 8% after 3 weeks of treatment, and reached steady low levels of 3.4% after 5 weeks of treatment. Ongoing exploratory analyses seek to identify risk factors for AE reporting and for discontinuations due to AEs. In summary, these integrated analyses are designed to validate the efficacy and safety of G-GR in treatment of PHN, and to explore in more detail the complex relationships between G-GR efficacy and safety measures. Study supported by Depomed, Inc., Newark, CA.
Abstracts
(386) Analgesia and psychosis: intrathecal ziconotide in a young Hospice patient with spinocerebellar ataxia and painful peripheral neuropathy B Stewart and J Sarria; University of South Florida / Moffitt Cancer Center, Tampa, FL We describe a 37-year-old woman with an underlying spinocerebellar ataxia who developed severe, painful peripheral neuropathy in 2006. When she presented to our clinic in April 2013, Hospice was providing her 40 mg IV hydromorphone per hour demand plus 10 mg every 10 minutes. She had failed gabapentin, pregabalin, and amitriptyline before coming under our care. Concerned about opiate inefficacy and hyperalgesia, we aggressively weaned (over one month) the patient completely from her hydromorphone. She was then trialed and implanted with an intrathecal pump infusing ziconotide. Over her 11day inpatient trial, the patient’s pain was reduced markedly at a final infusion rate of 10.8 mcg/day, and she required no other analgesics. After her implant, she even subsequently went on an international religious mission trip. Twentyseven days after the implant, however, the patient developed psychosis, and the ziconotide was stopped. Her symptoms resolved completely within one day. As an alternative, intrathecal opiates and local anesthetics were infused through the pump immediately thereafter, and for two months, but they failed. So, we decided to restart the ziconotide using a flexible dosing schedule, slowly increasing her daily dose. We used a basal rate of 0.206 mcg/hr plus a 2100 bolus of 2.001 mcg over one hour. Over the subsequent 4 months, we have made incremental increases and decreases in both her basal and bolus dosing, titrating to a balance of analgesia and mental status stability. Her total daily dose is now 11.437 mcg/day. At this time, her pain is again well controlled, she is not taking any opiates, and she has no neuropsychiatric side effects.
(387) Sensitivity analyses of the primary efficacy endpoint in a phase 2 randomized, placebo-controlled study of gabapentin enacarbil (GEn) in patients with neuropathic pain associated with postherpetic neuralgia (PHN) A Calkins, J Gudin, B Gidal, M Jaros, R Kim, and G Shang; New York Spine and Wellness Center, North Syracuse, NY GEn is an actively transported pro-drug of gabapentin. In this phase 2 randomized, placebo-controlled study in patients with PHN, GEn 1200 mg/day, 2400 mg/day, and 3600 mg/day demonstrated statistically significant differences compared with placebo with regard to the primary endpoint, change from baseline to end of maintenance treatment (EOMT; 1 week up-titration and 12 weeks maintenance) in mean 24-hour average pain intensity score. These comparisons between treatment arms and placebo were made for the intent-to-treat population using an analysis of covariance (ANCOVA) model, using last observation carried forward (LOCF) for imputation of missing data. In addition to the LOCF method, here we report pre-specified sensitivity analyses of the primary endpoint using the baseline observation carried forward (BOCF) imputation method and a mixed-effect model repeated measures (MMRM) analysis. All 3 GEn treatment groups demonstrated statistically significant differences in mean changes from baseline to EOMT relative to placebo using all 3 analysis methods. Mean differences (95% confidence interval) relative to placebo for the GEn 1200 mg, 2400 mg, and 3600 mg groups, respectively, were: LOCF, -0.81 (-1.40, -0.23; P=.007), -0.70 (-1.33, -0.07; P=.029), and -1.07 (-1.68, -0.45; P=.001); BOCF, -0.94 (-1.51, -0.36; P=.001), -0.65 (-1.27, -0.03; P=.040), and -0.68 (-1.28, -0.08; P=.027); and MMRM, -0.81 (-1.32, -0.31; P=0.002), -0.68 (-1.23, -0.14; P=.014), and -1.07 (-1.61, -0.54; P<.001). Although the study was not powered to detect differences between GEn doses, the greatest numerical difference vs placebo using the LOCF and MMRM methods was observed with GEn 3600 mg, while this was the case for GEn 1200 mg using the BOCF method. Regardless of the analysis methodology, there were significant differences between all three doses of GEn and placebo with regard to the primary endpoint, confirming the validity of the primary analysis. Study sponsorship and medical writing support were provided by XenoPort, Inc.
The Journal of Pain
(384) Evaluation of efficacy of duloxetine and pregabalin in patients with painful diabetic peripheral neuropathy P Rahimzadeh, S Faiz, F Imani, and M Alebouyeh; Hazrat Rasul Medical Complex, Iran University of Medical Sciences, Tehran, Iran Diabetic polyneuropathy (DPNP) is a symmetrical peripheral neuropathy that results from nerve damage after prolonged periods of suboptimal glycemic control. Neuropathy is often associated with significant burning, stabbing or tingling pain and numbness, and can result in sleep interference and severe disability. The aim of this study was to compare the efficacy and safety of duloxetine (DLX), a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine, with pregabaline (PGB) a calcium Channel blocker in the management of diabetic peripheral neuropathic pain. We performed a doubleblind 12-week RCT study of patients with diabetic peripheral neuropathic pain whom have been treated with pregabaline (150 mg/d)(n=55) or doluxetine (60mg/d) (n=50)and had a daily pain score of $4 (VAS)in admission time. The primary objective was a comparison between DLX and PGB on improvement in the weekly mean of the daily pain score. Secondary efficacy measures included sleep interference score, Patient Global Impression of Change (PGIC), and Clinical Global Impression of Change (CGIC).A significant reduction in pain score (VAS), sleep interference score, PGIC, and CGIC was seen in all the two treatment groups across time with no statistically significant difference between the groups. The improvement in pain scores and sleep interference score was faster with PGB compared to DLX. (P<0.05) Adverse drug reactions were mild in 4.5% of all cases. DLX and PGB Produced a clinically and subjectively meaningful pain relief in patients with DPNP with onset of pain relief being faster with PGB.
(385) Integrated efficacy and safety of gastroretentive gabapentin in treatment of patients with postherpetic neuralgia (PHN) M Sweeney, S Panchal, S Nalamachu, D Kantor, and R Rauck; Depomed, Inc., Newark ,CA For patients with PHN, the efficacy and safety of gastroretentive gabapentin (G-GR) was established in two randomized, placebo-controlled Phase 3 studies, and confirmed in an open-label, Phase 4 study. To gain further insight into the efficacy and safety of G-GR, and in how certain variables interact, data from patients who received G-GR 1800 mg once-daily in these studies were integrated and are being analyzed. The integrated dataset includes 546 patients in the efficacy population and 556 in the safety population. Efficacy evaluations in the dataset include Visual Analog Scale (VAS) and Brief Pain Inventory (BPI) completed at baseline and end of study (Week 10 for Phase 3, Week 8 for Phase 4), and Patients’/Clinical Global Impression of Change (P/CGIC) completed at end of study. Preliminary efficacy results have demonstrated a consistent, statistically significant reduction in VAS score by end of study. Further analyses will explore relationships between reduction in pain, improvements in quality of life, and baseline patient and disease characteristics. In addition, we will ascertain whether any factors are predictive of reductions in pain and improvements in quality of life.The integrated safety data show that G-GR was generally well tolerated. Seventy-two (12.9%) patients discontinued due to adverse events (AEs). The incidence of AEs decreased rapidly from 21% to 8% after 3 weeks of treatment, and reached steady low levels of 3.4% after 5 weeks of treatment. Ongoing exploratory analyses seek to identify risk factors for AE reporting and for discontinuations due to AEs. In summary, these integrated analyses are designed to validate the efficacy and safety of G-GR in treatment of PHN, and to explore in more detail the complex relationships between G-GR efficacy and safety measures. Study supported by Depomed, Inc., Newark, CA.
Abstracts
(386) Analgesia and psychosis: intrathecal ziconotide in a young Hospice patient with spinocerebellar ataxia and painful peripheral neuropathy B Stewart and J Sarria; University of South Florida / Moffitt Cancer Center, Tampa, FL We describe a 37-year-old woman with an underlying spinocerebellar ataxia who developed severe, painful peripheral neuropathy in 2006. When she presented to our clinic in April 2013, Hospice was providing her 40 mg IV hydromorphone per hour demand plus 10 mg every 10 minutes. She had failed gabapentin, pregabalin, and amitriptyline before coming under our care. Concerned about opiate inefficacy and hyperalgesia, we aggressively weaned (over one month) the patient completely from her hydromorphone. She was then trialed and implanted with an intrathecal pump infusing ziconotide. Over her 11day inpatient trial, the patient’s pain was reduced markedly at a final infusion rate of 10.8 mcg/day, and she required no other analgesics. After her implant, she even subsequently went on an international religious mission trip. Twentyseven days after the implant, however, the patient developed psychosis, and the ziconotide was stopped. Her symptoms resolved completely within one day. As an alternative, intrathecal opiates and local anesthetics were infused through the pump immediately thereafter, and for two months, but they failed. So, we decided to restart the ziconotide using a flexible dosing schedule, slowly increasing her daily dose. We used a basal rate of 0.206 mcg/hr plus a 2100 bolus of 2.001 mcg over one hour. Over the subsequent 4 months, we have made incremental increases and decreases in both her basal and bolus dosing, titrating to a balance of analgesia and mental status stability. Her total daily dose is now 11.437 mcg/day. At this time, her pain is again well controlled, she is not taking any opiates, and she has no neuropsychiatric side effects.
(387) Sensitivity analyses of the primary efficacy endpoint in a phase 2 randomized, placebo-controlled study of gabapentin enacarbil (GEn) in patients with neuropathic pain associated with postherpetic neuralgia (PHN) A Calkins, J Gudin, B Gidal, M Jaros, R Kim, and G Shang; New York Spine and Wellness Center, North Syracuse, NY GEn is an actively transported pro-drug of gabapentin. In this phase 2 randomized, placebo-controlled study in patients with PHN, GEn 1200 mg/day, 2400 mg/day, and 3600 mg/day demonstrated statistically significant differences compared with placebo with regard to the primary endpoint, change from baseline to end of maintenance treatment (EOMT; 1 week up-titration and 12 weeks maintenance) in mean 24-hour average pain intensity score. These comparisons between treatment arms and placebo were made for the intent-to-treat population using an analysis of covariance (ANCOVA) model, using last observation carried forward (LOCF) for imputation of missing data. In addition to the LOCF method, here we report pre-specified sensitivity analyses of the primary endpoint using the baseline observation carried forward (BOCF) imputation method and a mixed-effect model repeated measures (MMRM) analysis. All 3 GEn treatment groups demonstrated statistically significant differences in mean changes from baseline to EOMT relative to placebo using all 3 analysis methods. Mean differences (95% confidence interval) relative to placebo for the GEn 1200 mg, 2400 mg, and 3600 mg groups, respectively, were: LOCF, -0.81 (-1.40, -0.23; P=.007), -0.70 (-1.33, -0.07; P=.029), and -1.07 (-1.68, -0.45; P=.001); BOCF, -0.94 (-1.51, -0.36; P=.001), -0.65 (-1.27, -0.03; P=.040), and -0.68 (-1.28, -0.08; P=.027); and MMRM, -0.81 (-1.32, -0.31; P=0.002), -0.68 (-1.23, -0.14; P=.014), and -1.07 (-1.61, -0.54; P<.001). Although the study was not powered to detect differences between GEn doses, the greatest numerical difference vs placebo using the LOCF and MMRM methods was observed with GEn 3600 mg, while this was the case for GEn 1200 mg using the BOCF method. Regardless of the analysis methodology, there were significant differences between all three doses of GEn and placebo with regard to the primary endpoint, confirming the validity of the primary analysis. Study sponsorship and medical writing support were provided by XenoPort, Inc.