mirogabalin and Diabetic-Neuropathies

To assess the cost-effectiveness of 30 mg of mirogabalin versus no treatment or 300 mg of pregabalin in patients with diabetic peripheral neuropathic pain (DPNP) from a third-party perspective in Taiwan.. A Markov model, developed with cycles of 2-week and a 1-year timeframes, consisted of 3 health states: mild, moderate, and severe pain. Average daily pain score (ADPS) was assessed at the end of each 2-week cycle. All patients entered the model in moderate (4 ≤ ADPS < 7) or severe (7 ≤ ADPS ≤ 10) pain health states. At the end of each cycle, patients remained in their assigned health state or transitioned to a different health state according to their pain score change. Efficacy data were informed by the pivotal phase III clinical trial (J303, NCT02318706) or by a network meta-analysis. Utility values were obtained from published literature, and resource use and cost data from Taiwanese clinical experts and Taiwan National Health Insurance Administration. One-way sensitivity, scenario, and probabilistic analyses were conducted to test the robustness of the results.. A head-to-head analysis demonstrated that 30 mg of mirogabalin is a cost-effective treatment option versus placebo for DPNP. The base-case deterministic analysis estimated quality-adjusted life years (QALY) gains of 0.02 at an incremental cost of 9697 New Taiwan dollars (NT$) (equal to $323) versus placebo (incremental cost-effectiveness ratio [ICER]: 489 310 NT$/QALY [$15 860/QALY]). Mirogabalin was also cost-effective compared with 300 mg of pregabalin (ICER: 18 476 NT$/QALY [$600/QALY]). Sensitivity and scenario analyses results confirmed the robustness.. Economic analysis suggests that mirogabalin 30 mg, a potent and selective α2δ ligand, is a cost-effective treatment option for DPNP in Taiwan, with an ICER below the willingness-to-pay threshold.

Topics: Bridged Bicyclo Compounds; Cost-Benefit Analysis; Diabetes Mellitus; Diabetic Neuropathies; Humans; Neuralgia; Taiwan

Mirogabalin besylate has been approved in several countries to treat peripheral neuropathic pain. This pooled analysis, using data from the two pivotal Phase III studies in Asian patients with diabetic peripheral neuropathic pain and post-herpetic neuralgia, aimed to provide clinicians with more detailed and precise information relating to mirogabalin's safety and efficacy.. Data were pooled from 2 multicenter, double-blind, placebo-controlled, parallel-group, 14-week treatment studies of mirogabalin conducted at ∼350 study sites (Japan, South Korea, Taiwan, Singapore, Malaysia, and Thailand). Eligible patients in both studies were randomized in a 2:1:1:1 ratio, stratified according to a baseline average daily pain score (ADPS) of <6 or ≥6, to placebo, mirogabalin 15-mg once daily (QD), mirogabalin 10-mg twice daily (BID), or mirogabalin 15-mg BID treatment groups. Safety was assessed based on treatment-emergent adverse events identified from the adverse events collected throughout both studies. The primary efficacy end point of both studies was the change from baseline in ADPS at week 14.. In total, 1587 patients (824 with diabetic peripheral neuropathic pain; 763 with post-herpetic neuralgia) who received at least 1 dose of study drug were analyzed (633 received placebo, 954 treated with mirogabalin). Treatment-emergent adverse events included somnolence (3.8%, 10.8%, 14.5%, and 19.1%) and dizziness (2.7%, 5.7%, 9.1%, and 13.1%) in patients receiving placebo, mirogabalin 15 mg QD, mirogabalin 10 mg BID, and mirogabalin 15 mg BID, respectively. In patients treated with mirogabalin 15 mg QD, 2 (0.6%) of 316 patients discontinued due to somnolence. In the mirogabalin 10-mg BID group, somnolence, edema, and peripheral edema each resulted in 3 (0.9%) of 318 patient discontinuations. In the mirogabalin 15-mg BID group, 6 (1.9%) of 320 patients discontinued due to dizziness and 3 (0.9%) due to somnolence. At week 14, mirogabalin 10 mg BID and 15 mg BID statistically significantly improved ADPS versus placebo, with least squares mean changes (95% CI) of -0.31 (-0.55, -0.08) and -0.63 (-0.86, -0.40). Post hoc analysis showed a statistically significant difference 2 days after administration in the mirogabalin 10-mg and 15-mg BID groups compared with placebo. Female sex, age ≥65 years, and baseline weight <60 kg may influence the safety of mirogabalin, particularly regarding the incidence of somnolence and dizziness, but had no notable impact on efficacy. ClinicalTrials.gov identifiers: NCT02318706 and NCT02318719.. This pooled analysis showed that mirogabalin was efficacious and well-tolerated by Asian patients with peripheral neuropathic pain.

Topics: Aged; Analgesics; Bridged Bicyclo Compounds; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Neuralgia; Pharmaceutical Preparations; Treatment Outcome

Diabetic peripheral neuropathic pain (DPNP) affects the functionality, mood and sleep patterns of patients with diabetes. Mirogabalin, an α. This 52-week open-label extension study was carried out in Japan, Korea and Taiwan in patients with DPNP. Patients received mirogabalin, initiated at 5 mg twice daily and increased to a flexible maintenance dosage of 10 or 15 mg twice daily. Adverse events were monitored throughout the study. Patients provided a self-assessment of pain using the Short-Form McGill Pain Questionnaire.. Of the 214 patients who entered the study, 172 (80.4%) completed the extension study. Of 172 patients who completed the study, 149 received the highest dosage of mirogabalin (15 mg twice daily). The most common treatment-emergent adverse events were nasopharyngitis, diabetic retinopathy, peripheral edema, somnolence, diarrhea, increased weight and dizziness. Most treatment-emergent adverse events were mild or moderate in severity. The incidence of treatment-emergent adverse events leading to treatment discontinuation was 13.1%. The visual analog scale and all other Short-Form McGill Pain Questionnaire subscales (sensory score, affective score, total score and present pain intensity) generally decreased over time from baseline until week 52.. This extension study showed the safety and efficacy of a long-term flexible dosing regimen of mirogabalin 10 or 15 mg twice daily in patients with DPNP.

Topics: Analgesics; Asian People; Bridged Bicyclo Compounds; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Treatment Outcome

This study evaluated the efficacy and safety of mirogabalin, a novel, potent, selective ligand of the α. During this double-blind, multisite, placebo-controlled phase III study, Asian patients aged ≥20 years with type 1 or 2 diabetes and DPNP were randomized 2:1:1:1 to a placebo, mirogabalin 15, 20 or 30 mg/day for up to 14 weeks, with a 1- to 2-week titration (NCT02318706). The primary endpoint was the change from baseline in average daily pain score (ADPS) at week 14, defined as a weekly average of daily pain (0 = no pain to 10 = worst possible pain, for the past 24 h).. Of 834 randomized patients, 330, 164, 165 and 165 received placebo, mirogabalin 15, 20 or 30 mg/day, respectively, and were included in analyses (modified intention-to-treat population, n = 824); 755 (90.5%) completed the study. At week 14, the least squares mean average daily pain score change from baseline was -1.31, -1.34, -1.47 and -1.81, respectively, showing statistical significance for mirogabalin 30 mg/day versus placebo (P = 0.0027). The treatment-emergent adverse events observed were mostly mild-to-moderate in all mirogabalin doses, and the most frequent treatment-emergent adverse events were nasopharyngitis, somnolence, dizziness, peripheral edema and weight increase.. Mirogabalin relieved DPNP in a dose-dependent manner; mirogabalin 30 mg/day showed statistically significant pain relief (vs placebo) in Asian DPNP patients. All doses of mirogabalin tested were well tolerated.

Topics: Adolescent; Adult; Aged; Asian People; Bridged Bicyclo Compounds; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuralgia; Treatment Outcome; Young Adult

The primary aim of this study was to assess the individual effects of probenecid and cimetidine on mirogabalin exposure.. This phase 1, open-label, crossover study randomized healthy adults to receive three treatment regimens, each separated by ≥5-day washout: a single oral dose of mirogabalin 15 mg on day 2, mirogabalin 15 mg on day 2 plus probenecid 500 mg every 6 h from days 1 to 4, and mirogabalin 15 mg on day 2 plus cimetidine 400 mg every 6 h from days 1 to 4.. Coadministration of mirogabalin with probenecid or cimetidine increased the maximum and total mirogabalin exposure. The geometric mean ratios of C. A greater magnitude of change in mirogabalin exposure was observed when coadministered with a drug that inhibits both renal and metabolic clearance (probenecid) vs. a drug that only affects renal clearance (cimetidine). However, as the increase in exposure is not clinically significant (>2-fold), no a priori dose adjustment is recommended.

Topics: Administration, Oral; Adult; Area Under Curve; Bridged Bicyclo Compounds; Cimetidine; Cross-Over Studies; Diabetic Neuropathies; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Healthy Volunteers; Herpes Zoster; Humans; Male; Metabolic Clearance Rate; Middle Aged; Neuralgia; Probenecid; Renal Elimination

Using patient global impression of change (PGIC) as an anchor, an approximately 30% reduction on an 11-point numeric pain intensity rating scale (PI-NRS) is considered a clinically important difference (CID) in pain. Our objective was to define the CID for another pain measure, the worst pain severity (WPS) item of the modified Brief Pain Inventory (m-BPI).. In this post hoc analysis of a double-blind, placebo-controlled, phase 2 study, 452 randomized patients with diabetic peripheral neuropathic pain (DPNP) were followed over 5 weeks, with m-BPI data collected weekly and PGIC at treatment conclusion. Receiver operating characteristic (ROC) curves (via logistic regression) were used to determine the changes in the m-BPI-WPS score that best predicted ordinal clinical improvement thresholds (i.e., "minimally improved" or better) on the PGIC.. Similar to the PI-NRS, a change of -3 (raw) or -33.3% from the baseline on the m-BPI-WPS optimized prediction for the "much improved" or better PGIC threshold and represents a CID. There was a high correspondence between observed and predicted PGIC categories at each PGIC threshold (ROC AUCs were 0.78-0.82).. Worst pain on the m-BPI may be used to assess clinically important improvements in DPNP studies. Findings require validation in larger studies.

Topics: Bridged Bicyclo Compounds; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Male; Outcome Assessment, Health Care; Pain; Pain Measurement; ROC Curve; Statistics as Topic

To evaluate the effects of mirogabalin on patient-reported pain and sleep interference in diabetic peripheral neuropathic pain (DPNP).. Adults (≥18 years) with type 1 or 2 diabetes, glycosylated hemoglobin of 10% or less at screening, and DPNP for six months or more were eligible for participation.. Subjects (N = 452) were randomly assigned (2:1:1:1:1:1:1) to receive placebo, dose-ranging mirogabalin (5, 10, 15, 20, 30 mg/day), or pregabalin (300 mg/day) for five weeks. Secondary efficacy end points studied here included patient global impression of change (PGIC), modified brief pain inventory (BPI), and average daily sleep interference score (ADSIS). Correlation plots were generated to examine the relationship between ADSIS and average daily pain score (ADPS).. At week 5, significant reductions in ADSIS were observed in the mirogabalin 15, 20, and 30 mg/day groups, compared with placebo (P < 0.05). Baseline ADSIS and ADPS were strongly correlated (R2 = 0.4407), as were mean changes from baseline in ADSIS and ADPS at week 5 (R2 = 0.6694). The mirogabalin 30 mg/day group showed significant improvement compared with placebo in four of six BPI subscales at end point; the mirogabalin 15 mg/day group showed significant improvement in three of six BPI subscales (P < 0.05). At end of treatment, the percentage of subject with PGIC status of "much improved or better" was greater in all mirogabalin dose groups than in the placebo group (P < 0.05). A low incidence of treatment-related adverse events was reported for mirogabalin.. Results support the effectiveness of mirogabalin in improving patient-reported pain and sleep interference in DPNP.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Bridged Bicyclo Compounds; Diabetic Neuropathies; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Pregabalin; Sleep; Treatment Outcome

We aimed to identify doses of mirogabalin (DS-5565) providing clinically meaningful efficacy with manageable side effects for treatment of diabetic peripheral neuropathic pain (DPNP).. Adults (≥18 years) with type 1 or 2 diabetes, HbA₁c ≤10% at screening, and DPNP for ≥6 months were eligible for study participation. Subjects (n = 452) were randomized (2:1:1:1:1:1:1 ratio) to placebo, dose-ranging mirogabalin (5, 10, 15, 20, and 30 mg/day), or pregabalin (300 mg/day) for 5 weeks. The primary end point was weekly change in average daily pain score (ADPS; 0 to 10 numeric rating scale) from baseline to week 5 (minimally meaningful effect, ≥1.0-point decrease versus placebo). ANCOVA was conducted using last observation carried forward, and treatment effect least squares (LS) means were provided for each contrast. Safety assessments included adverse events (AEs), clinical laboratory tests, and electrocardiograms.. LS mean differences in change in ADPS from baseline to week 5 versus placebo were -0.22, -0.53, -0.94, -0.88, and -1.01 for the mirogabalin 5-, 10-, 15-, 20-, and 30-mg/day treatment groups, respectively, and -0.05 in the pregabalin group (P < 0.05 versus placebo for mirogabalin 15, 20, and 30 mg/day). Most frequent AEs (n = 277) were primarily mild to moderate dizziness (9.4%), somnolence (6.1%), and headache (6.1%); otherwise, mirogabalin was well tolerated.. Mirogabalin 15, 20, and 30 mg/day had statistically significant reductions in ADPS versus placebo, and mirogabalin 30 mg/day also met the criteria of minimally meaningful effect. Mirogabalin may be a promising new treatment option for patients with DPNP.

Topics: Adult; Aged; Analgesics; Bridged Bicyclo Compounds; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Placebos; Pregabalin; Treatment Outcome