This 8-week randomized, double-blind study compared the efficacy of gabapentin to placebo for the treatment of post-herpetic neuralgia. As in study 945-210, gabapentin (or matching placebo) was sequentially titrated through a range of dosages (900, 1800, 2400 mg/day) until a dosage of 3600 mg/day was reached, or the highest well tolerated dosage below 3600 mg/day. This "force titration" phase was 4-weeks in duration. During the second 4-week period of double-blind treatment, the maximum well tolerated dosage of gabapentin was maintained. As mentioned previously, this forced-titration design - to a single gabapentin dosage, or to the next highest dosage based on tolerability - is insufficient to establish a dose- response relationship for the drug. The primary efficacy measurement was the change from baseline in the average daily pain rating scores (similar to 945-210). The pain score was derived from an 11-point Likert scale in which 0 represented "no pain" and 10 represented the "worst pain possible." Results showed that gabapentin treated patients experienced a statistically significant reduction in the mean pain score from baseline relative to placebo-treated patients (p=0.001). However, as for study 945-210, the study design was insufficient to determine the dose-response relationship of gabapentin since a single final dosage (3600 mg/day) was used in the trial. Thus, this study does not provide substantial evidence of increased efficacy of gabapentin for post-herpetic neuralgia at doses above 1800 mg/day.
This 7-week randomized, double-blind trial compared the efficacy of gabapentin 1800 mg/day, and 2400 mg/day to placebo for the treatment of post-herpetic neuralgia. The "fixed-dose parallel group" design of this trial was employed to gather data regarding the dose-response effect of gabapentin. The primary efficacy measurement was the change from baseline in the average daily pain rating scores. The pain score was derived from an 11-point Likert scale in which 0 represented "no pain" and 10 represented the "worst pain possible." Results showed that gabapentin-treated patients experienced a statistically significant reduction in the mean pain score from baseline (p<0.01) relative to placebo-treated patients for both the 1800 mg/day and 2400 mg/day groups. The mean reduction in pain score from baseline was -34.5% in the 1800 mg/day gabapentin group, and -34.4% in the 2400 mg/day gabapentin group. Thus, the two dosage groups (while not compared statistically for difference) are clearly similar. Comparing the two gabapentin dosage groups with regard to the clinically relevant "responder rate" (the percentage of patients with a reduction in mean pain score of > 50%) also shows that responses were similar for the 1800 mg/day (32% responder rate) and 2400 mg/day (34% responder rate) groups. Thus, no dose-response effect for gabapentin was found, and this study does not provide substantial evidence of increased efficacy of gabapentin for post-herpetic neuralgia at doses above 1800 mg/day.
Gabapentin enacarbil (GEn) is an actively transported prodrug of gabapentin that provides sustained, dose-proportional exposure to gabapentin. This randomized, double-blind, parallel-group, placebo-controlled study evaluated the safety and efficacy of 3 different maintenance doses of oral GEn in subjects with postherpetic neuralgia. Adults with a 24-hour average pain intensity score of ≥ 4.0 received GEn 1,200 mg, 2,400 mg, 3,600 mg, or placebo for 14 weeks (including a 1-week up-titration, 12-week maintenance, and 1-week taper). The primary endpoint was change from baseline to end of maintenance treatment in mean 24-hour average pain intensity score. The intent-to-treat population consisted of 371 subjects (GEn 1,200 mg = 107, 2,400 mg = 82, 3,600 mg = 87, placebo = 95). With regard to the primary endpoint, all 3 GEn treatment groups demonstrated a statistically significant difference relative to placebo. The adjusted mean change from baseline for the treatment groups ranged from −2.36 to −2.72 versus −1.66 for the placebo group. Exposure-response modeling suggested an ED50 around 1,200 mg/day, which was consistent with historical findings reported for gabapentin. The most commonly reported adverse events were dizziness and somnolence. All studied doses of GEn significantly improved pain associated with postherpetic neuralgia as compared to placebo and were well tolerated. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
OBJECTIVE: To evaluate the safety and efficacy of a once-daily gastroretentive formulation of gabapentin (G-GR; 1800 mg). METHODS: This was an 11-week, double-blind, randomized, placebo-controlled Phase 3 clinical trial in patients with postherpetic neuralgia. Patients underwent a 2-week dose titration, 8 weeks of stable dosing, and 1 week of dose tapering. The primary endpoint was the change in average daily pain intensity score from Baseline to Week 10 using Baseline Observation Carried Forward (BOCF) imputation. RESULTS: Four-hundred and fifty-two patients (mean age 65.6 y, BMI 29 Kg/m) were randomized. Baseline average daily pain intensity score during the week prior to randomization was 6.6 and 6.5 for the G-GR and placebo treatment groups, respectively. Three hundred and seventy-seven patients completed the study (84% G-GR, 83% placebo). G-GR significantly reduced BOCF change in average daily pain intensity compared with placebo (-2.1 vs. -1.6; G-GR vs. placebo, P=0.013). Compared with placebo, more G-GR-treated patients reported "much" or "very much" improvement (patient global impression of change, 43% vs. 34%; P<0.0434), and G-GR reduced sleep interference (-2.3 vs. -1.59; P<0.0001), although neither endpoint was considered statistically significant based on a stringent hierarchical statistical paradigm. Other secondary endpoints showed similar trends. The most common adverse events were dizziness (G-GR, 11.3% vs. placebo, 1.7 %) and somnolence (G-GR, 5.4% vs. placebo, 3.0%). CONCLUSION: Once-daily G-GR 1800 mg was effective and well tolerated for the relief of pain in patients with postherpetic neuralgia.
OBJECTIVE: To evaluate the safety and efficacy of a once-daily gastroretentive formulation of gabapentin (G-GR; 1800 mg). METHODS: This was an 11-week, double-blind, randomized, placebo-controlled Phase 3 clinical trial in patients with postherpetic neuralgia. Patients underwent a 2-week dose titration, 8 weeks of stable dosing, and 1 week of dose tapering. The primary endpoint was the change in average daily pain intensity score from Baseline to Week 10 using Baseline Observation Carried Forward (BOCF) imputation. RESULTS: Four-hundred and fifty-two patients (mean age 65.6 y, BMI 29 Kg/m²) were randomized. Baseline average daily pain intensity score during the week prior to randomization was 6.6 and 6.5 for the G-GR and placebo treatment groups, respectively. Three hundred and seventy-seven patients completed the study (84% G-GR, 83% placebo). G-GR significantly reduced BOCF change in average daily pain intensity compared with placebo ( −2.1 vs. − 1.6; G-GR vs. placebo, <i>P</i> = 0.013). Compared with placebo, more G-GR-treated patients reported “much” or “very much” improvement (patient global impression of change, 43% vs. 34%; <i>P</i> < 0.0434), and G-GR reduced sleep interference (− 2.3 vs. − 1.59; <i>P</i> < 0.0001), although neither endpoint was considered statistically significant based on a stringent hierarchical statistical paradigm. Other secondary endpoints showed similar trends. The most common adverse events were dizziness (G-GR, 11.3% vs. placebo, 1.7 %) and somnolence (G-GR, 5.4% vs. placebo, 3.0%). CONCLUSION: Once-daily G-GR 1800mg was effective and well tolerated for the relief of pain in patients with postherpetic neuralgia. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
Background Gabapentin enacarbil ( GEn), a transported prodrug of gabapentin, provides sustained, dose-proportional gabapentin exposure. The purpose of this study was to investigate the dose response of GEn to select the optimal dose(s) for clinical use in subsequent diabetic peripheral neuropathy ( DPN) trials. Methods This was a multicenter, randomized, double-blind, double-dummy, parallel group, placebo-controlled trial with a study duration of approximately 20 weeks (Clinicaltrials.gov database, Identifier ! NCT00643760). Pregabalin ( PGB) (Lyrica<sup>®</sup>; Pfizer Inc.) was used as an active control to provide assay sensitivity of the trial. A total of 421 adult subjects with DPN were randomized in a ratio of 2:1:1:1:2 to receive oral GEn 3,600 mg/day, GEn 2,400 mg/day, GEn 1,200 mg/day, PGB 300 mg/day, or matching placebo, respectively. The primary efficacy endpoint was change from baseline to end of maintenance treatment with respect to the mean 24-hour average pain intensity score based on an 11-point Pain Intensity Numerical Rating Scale ( PI- NRS). Safety and tolerability assessments included treatment-emergent adverse events ( TEAEs), laboratory evaluations, vital signs, electrocardiograms ( ECG), neurological examination, and pedal edema. Results The adjusted mean difference vs. placebo at the end of maintenance treatment with respect to the mean 24-hour average PI- NRS pain intensity score for GEn 1,200 mg (−0.35; [95% CI: −1.02, 0.31]; P = 0.295), GEn 2,400 mg (−0.02; [95% CI: −0.71, 0.66]; P = 0.946), and GEn 3,600 mg (−0.55; [95% CI: −1.10, 0.01]; P = 0.105) was not statistically significant. The active control, PGB (300 mg/day), did not differentiate from placebo. Conclusion Overall, none of the GEn treatment groups differentiated from placebo. Analyses of the secondary endpoints showed comparable results across treatment groups. However, the majority of the endpoints, including all of the pain endpoints, showed the largest numerical treatment difference was between GEn 3,600 mg and placebo. The active control, PGB (300 mg/day), did not differentiate from placebo.
UNLABELLED: Gabapentin enacarbil (GEn) is an actively transported prodrug of gabapentin that provides sustained, dose-proportional exposure to gabapentin. This randomized, double-blind, parallel-group, placebo-controlled study evaluated the safety and efficacy of 3 different maintenance doses of oral GEn in subjects with postherpetic neuralgia. Adults with a 24-hour average pain intensity score of ≥4.0 received GEn 1,200 mg, 2,400 mg, 3,600 mg, or placebo for 14 weeks (including a 1-week up-titration, 12-week maintenance, and 1-week taper). The primary endpoint was change from baseline to end of maintenance treatment in mean 24-hour average pain intensity score. The intent-to-treat population consisted of 371 subjects (GEn 1,200 mg = 107, 2,400 mg = 82, 3,600 mg = 87, placebo = 95). With regard to the primary endpoint, all 3 GEn treatment groups demonstrated a statistically significant difference relative to placebo. The adjusted mean change from baseline for the treatment groups ranged from -2.36 to -2.72 versus -1.66 for the placebo group. Exposure-response modeling suggested an ED50 around 1,200 mg/day, which was consistent with historical findings reported for gabapentin. The most commonly reported adverse events were dizziness and somnolence. All studied doses of GEn significantly improved pain associated with postherpetic neuralgia as compared to placebo and were well tolerated. PERSPECTIVE: GEn provides clinically important pain relief with doses from 1,200 mg to 3,600 mg and is generally well tolerated and efficacious. As an actively transported prodrug of gabapentin, it provides dose-proportional and extended exposure to gabapentin.
BACKGROUND: Oral gabapentin is approved as an anticonvulsant medication and to treat postherpetic neuralgia. Its nonopioid properties and presumed spinal site of analgesic action made the study on intrathecal gabapentin attractive to establish the minimum effective dose for a later, pivotal trial.
METHODS: The authors examined the safety and efficacy of intrathecal gabapentin in a randomized, blinded, placebo-controlled, multicenter trial in a heterogeneous cohort of candidates with chronic pain for intrathecal drug therapy.
RESULTS: Patients (N = 170) were randomized to receive continuous intrathecal gabapentin (0 [placebo], 1, 6, or 30 mg/day) during 22 days of blinded treatment after implantation of a permanent drug delivery system. The highest dose, 30 mg/day, was selected to maintain a safety margin below the 100-mg/day dose that was explored in a phase 1 study. The authors found no statistically significant difference in the primary outcome measure, which was the numerical pain rating scale and response rate after 3 weeks, for any dose versus placebo. Physical functioning, quality of life, and emotional functioning also revealed no differences. Small, nonsignificant changes occurred in opioid medication use. The most frequent device-related adverse events were transient postimplant (lumbar puncture) headache, pain, and nausea. The most frequent gabapentin-related adverse events were nausea, somnolence, headache, dizziness, fatigue, and peripheral edema.
CONCLUSION: Twenty-two days of intrathecal gabapentin did not demonstrate statistically significant or clinically meaningful analgesic effects. The study sponsor has no current plans for further studies. Drug-related adverse events were similar to those for oral gabapentin. Most device-related adverse events resulted from the implant surgery or anesthesia.
Neuropathic pain is difficult to diagnose and difficult to treat with certainty. So the aim of the study was to evaluate comparative clinical efficacy of pregabaline with amitriptyline and gabapentin in neuropathic cancer pain. A total of 120 patients with cancer having severe neuropathic cancer pain were enrolled in the study after taking approval from Institutional Ethics Committee and divided in to 4 groups: group AT—amitriptyline, group GB—gabapentin, group PG—pregabalin, and group PL—placebo. Oral morphine was used for rescue analgesic for continued pain. Pain score (Visual Analogue scale) and secondary outcome measures such as intensity of lancinating, dysesthesia, and burning on numerical rating scale, Global satisfaction score (GSS), Eastern Co-operative Oncology Group scoring (ECOG), and adverse effects were assessed. At the end of study there was significant decrease in pain score in group PG as compared to the other groups; group AT (<i>P</i> = .003), group GB (<i>P</i> = .042), and group PL (<i>P</i> = .024). Percentage of patients with lancinating pain and dysesthesia were significantly less in group PG as compared to groups GB and PL. All the patients in group PL needed rescue morphine. After 4 visits, maximum improvement in ECOG scoring and GSS scoring was observed in group PG patients. Our results suggested that all antineuropathic drugs are effective in relieving cancer-related neuropathic pain. There was statistically and clinically significant morphine sparing effect of pregabaline in relieving neuropathic cancer pain and neuropathic symptoms as compared to other antineuropathic drugs. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
This 8-week randomized, double-blind study compared the efficacy of gabapentin to placebo for the treatment of post-herpetic neuralgia. As in study 945-210, gabapentin (or matching placebo) was sequentially titrated through a range of dosages (900, 1800, 2400 mg/day) until a dosage of 3600 mg/day was reached, or the highest well tolerated dosage below 3600 mg/day. This "force titration" phase was 4-weeks in duration. During the second 4-week period of double-blind treatment, the maximum well tolerated dosage of gabapentin was maintained. As mentioned previously, this forced-titration design - to a single gabapentin dosage, or to the next highest dosage based on tolerability - is insufficient to establish a dose- response relationship for the drug. The primary efficacy measurement was the change from baseline in the average daily pain rating scores (similar to 945-210). The pain score was derived from an 11-point Likert scale in which 0 represented "no pain" and 10 represented the "worst pain possible." Results showed that gabapentin treated patients experienced a statistically significant reduction in the mean pain score from baseline relative to placebo-treated patients (p=0.001). However, as for study 945-210, the study design was insufficient to determine the dose-response relationship of gabapentin since a single final dosage (3600 mg/day) was used in the trial. Thus, this study does not provide substantial evidence of increased efficacy of gabapentin for post-herpetic neuralgia at doses above 1800 mg/day.
