Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies.

Abstract Background Paracetamol (APAP), also known as acetaminophen, is the most commonly used over-the-counter analgesic for the treatment of mild-to-moderate pain. However, the speed of onset of pain relief is limited mainly to the standard, immediate-release formulation. Efficacy and speed of onset of pain relief are critical in acute pain situations such as postsurgical dental pain, because reducing pain can improve clinical outcome and reduce the risk of transition from acute pain to more chronic pain. Efficacy and rapid onset also reduce the risk of excessive dosing with the analgesic. Objective We sought to investigate the dose–response efficacy and speed of onset of pain relief of a fast-dissolving APAP formulation compared with lower doses of APAP and placebo in dental patients after impacted third molar extraction. Methods Two single-center, single-dose, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies (Study I and Study II) were conducted to evaluate the efficacy and speed of onset of pain relief of different doses of a fast-dissolving APAP tablet (FD-APAP), standard APAP, and placebo in patients with postsurgical dental pain following third molar extraction. In Study I, a single dose of FD-APAP 1000 mg, FD-APAP 500 mg, or placebo was given to 300 patients; in Study II, a single dose of FD-APAP 1000 mg, standard APAP 650 mg, or placebo was given to 401 pateints. All 701 patients from both studies were included in the analysis and safety assessment. Results FD-APAP 1000 mg demonstrated significantly greater effect compared with FD-APAP 500 mg, APAP 650 mg, and placebo for all efficacy measurements, including sum of pain relief and pain intensity difference, total pain relief, sum of pain intensity difference, pain intensity difference, and pain relief score during 6 hours after the dose. Onset of confirmed first perceptible relief in subjects treated with FD-APAP 1000 mg was 15 minutes, which was 32% and 25% significantly shorter than onset of pain relief of FD-APAP 500 mg (22 minutes) and standard APAP 650 mg (20 minutes), respectively. FD-APAP 500 mg and APAP 650 mg demonstrated efficacy over placebo for most of the measurements; however, their effects were significantly lower and lasted for a shorter period of time than for FD-APAP 1000 mg. All study treatments were well tolerated. Conclusions FD-APAP 1000 mg tablets demonstrated efficacy over placebo. Also, FD-APAP 1000 mg had significantly superior effect, faster onset, and longer duration of pain relief compared with FD-APAP 500 mg and APAP 650 mg tablets. ClinicalTrials.gov identifiers: NCT01082081 and NCT01075243.