Acetyllevocarnitine hydrochloride for the treatment of diabetic peripheral neuropathy: A phase 3, randomized clinical trial in China

Diabetic peripheral neuropathy (DPN) is a highly prevalent chronic complication in type-2 diabetes mellitus (T2DM), for which no effective treatment is available. In this multi-center, randomized, double-blind, placebo-controlled phase 3 clinical trial in China, T2DM patients with DPN received acetyllevocarnitine hydrochloride (ALC, 1,500 mg/day, n = 231) or placebo (n = 227) for 24 weeks, during which anti-diabetic therapy was maintained. Significantly greater reduction in modified Toronto Clinical Neuropathy Score (mTCNS) as the primary endpoint occurred in the ALC group (-6.9 ± 5.3 points) compared to the placebo group (-4.7 ± 5.2 points, P < 0.001). Effect sizes (ALC = 1.31 and Placebo = 0.85) represented a 0.65-fold improvement in ALC treatment efficacy. The mTCNS values for pain did not differ significantly between the two groups (P = 0.066), whereas the remaining 10 components of mTCNS showed significant improvement in the ALC group compared to the Placebo group (P < 0.05 for all). Overall results of electrophysiological measurements were inconclusive, with significant improvement in individual measurements limited primarily to the ulnar and median nerves. Incidence of treatment emergent adverse events was 51.2% in the ALC group, among which urinary tract infection (5.9%) and hyperlipidemia (7.9%) were most frequent.