Clinical validation of a fast-acting acetaminophen: a randomized, active and placebo controlled dental pain study

Abstract

Objectives

To address the need for faster pain relief of over-the-counter (OTC) analgesic users, a novel drug delivery technology was developed to achieve faster absorption of orally administered acetaminophen with the goal of delivering earlier onset of pain relief. Previous development studies suggested that a 1000 mg dose of this fast-acting acetaminophen (FA-acetaminophen) formulation provided faster absorption and onset of action versus, commercially available OTC fast-acting analgesics, 1000 mg of extra-strength acetaminophen (ES-acetaminophen) or 400 mg of liquid-filled ibuprofen capsules (LG-ibuprofen). This study was designed as the definitive trial evaluating the onset of pain relief of FA-acetaminophen versus these same OTC comparators.

Methods

This single-dose, randomized, double-blind, placebo- and active-controlled clinical trial compared analgesic onset, overall efficacy, and safety of FA-acetaminophen 1000 mg, ES-acetaminophen 1000 mg, LG-ibuprofen 400 mg, and placebo over 4 h in a postsurgical dental pain model. Following removal of 3 to 4 impacted third molars, 664 subjects with moderate-to-severe pain were randomized in a 4:4:2:1 ratio to FA-acetaminophen (249), ES-acetaminophen (232), LG-ibuprofen (124), or placebo (59). Mean age was 18.9 years; 45.5% were male; 57.5% had severe baseline pain intensity. Subjects stopped a first stopwatch if/when they had perceptible pain relief and a second stopwatch if/when their pain relief became meaningful to them. Pain intensity difference (PID) and pain relief (PAR) were obtained using an 11-point numerical rating scale.

Findings

FA-acetaminophen 1000 mg had faster median time to onset of pain relief (15.7 min) compared to ES-acetaminophen 1000 mg (20.2 min, p = 0.035), LG-ibuprofen 400 mg (23.2 min, p < 0.001), and placebo (non-estimable), statistically greater mean PAR and PID scores than other treatment groups at 15 and 30 min, and a statistically greater percentage of subjects with confirmed perceptible pain relief at 15 and 20 min. At 25 min, FA-acetaminophen 1000 mg had a statistically significantly greater percentage of subjects with confirmed perceptible pain relief than LG-ibuprofen 400 mg and placebo. No clinically significant adverse events were reported.

Conclusions

This study supports previous studies, demonstrating faster onset of analgesia with FA-acetaminophen 1000 mg compared to OTC ES-acetaminophen 1000 mg and OTC LG-ibuprofen 400 mg.

ClinicalTrials.gov Identifier

NCT03224403 https://clinicaltrials.gov/ct2/show/NCT03224403

Keywords:

• Acetaminophen
• fast-acting formulation
• analgesic onset
• pain relief

This article is related to:

Analgesic onset and efficacy of a fast-acting formulation of acetaminophen in a postoperative dental impaction pain model

Transparency

Declaration of financial/other relationships

AM, PZ were employees of Johnson & Johnson Consumer Inc. TB is an employee of JBR Clinical Research which received funding from Johnson & Johnson Consumer Inc for conduct of this study. SAC was engaged by and acted as consultant to Johnson & Johnson Consumer Inc. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

AM: conceptualization, methodology, resources, writing – original draft, writing – review and editing, visualization, supervision, project administration, funding acquisition. TB: conceptualization, methodology, investigation, resources, writing – review and editing, supervision, project administration, visualization. PZ: conceptualization, methodology, software, formal analysis, resources, data curation, writing – review and editing, project administration. SC: conceptualization, methodology, validation, formal analysis, investigation, writing – review and editing, visualization.

Acknowledgements

The authors thank the subjects of this clinical study. The authors thank Kathleen Boyle, PhD, CMPP of 4 Learning Group, LLC (Exton, PA, USA) who, under the direction of the authors, supported manuscript preparation and managed the review process.

Additional information

Funding

This study was sponsored by Johnson & Johnson, Janssen Pharmaceuticals Division and Johnson & Johnson Consumer Inc, McNeil Consumer Healthcare Division, which was responsible for study design and collection, analysis, interpretation of the data, and decision to submit the manuscript for publication. Johnson & Johnson Consumer Inc, McNeil Consumer Healthcare Division, provided funding for the study and for support by an independent medical writer.