Efficacy and Safety of a New Sustained-release Pregabalin Formulation Compared With Immediate-release Pregabalin in Patients With Peripheral Neuropathic Pain

Abstract

Objective: This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients. Materials and Methods: This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores. Results: A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval −0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (−0.78; P noninferiority<0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred. Discussion: The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.

Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials

“…The complete list of included articles with detailed characteristics (pharmacological target, drug, route, dosage, clinical trial code, phase and completion date) is shown in Table 1 . The most repeated main pharmacological target, referring to the one that explains the analgesic effect, was subunit α2δ of voltage-gated calcium channels (VGCCs) [ 13 , 14 , 15 , 16 , 17 , 18 ], which was followed by Voltage-Gated Sodium Channels (VGSCs) in its different subtypes [ 19 , 20 ] and mu opioid receptor [ 21 , 22 , 23 ]. Other mechanisms included were Angiotensin II Type 2 Receptor (AT2R) [ 24 ], Cyclooxygenase-1 (COX-1) [ 25 ], Adaptor-Associated Kinase 1 (AAK1) [ 26 ], Lanthionine Synthetase Component C-like protein (LANCL) [ 27 ], an unknown mechanism [ 28 ], N-Methyl-D-Aspartate Receptor (NMDAR) [ 29 ] and Nerve Growth Factor (NGF) [ 30 ].…”

A randomized, active-controlled, parallel, open-label, multicenter, phase 4 study to compare the efficacy and safety of pregabalin sustained release tablet and pregabalin immediate release capsule in type II diabetic patients with peripheral neuropathic pain

“…[21] In a previous randomized double-blind study in South Korean patients with DPN and postherpetic neuralgia, the efficacy of the new SR pregabalin (YHD1119), as measured by the mean Daily Pain Rating Scale score, was non-inferior to IR pregabalin. [15] However, there was no assessment of drug compliance when the IR formulation is switched to the SR formulation from twice-daily to once-daily dosing.…”

“…was shown to be effective and safe in a randomized, non-inferiority phase 3 study conducted in Korea. [15] However, there is limited real-world data comparing the efficacy, safety, and medication adherence between immediate-release (IR) and SR formulations of pregabalin. Therefore, in this study, we aim to evaluate the efficacy, safety, and medication adherence of pregabalin SR compared with those of pregabalin IR.…”

A Meta-analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Pregabalin and Gabapentin in the Treatment of Postherpetic Neuralgia

“…At present, there are many treatment methods for PHN, and the rational selection of drugs is the basis for the treatment of patients with PHN. Compared with other treatment methods such as interventional therapy, drug therapy is relatively simple, safe, and easy to manage, with higher patient compliance, better treatment effects, and is more conducive to the remission of the disease [ 34 ].…”