A double-blind, randomised, crossover study of two doses of a single-tablet combination of ibuprofen/paracetamol and placebo for primary dysmenorrhoea

Abstract

Objectives:

Efficacy of pain relief may potentially be enhanced by combining two or more analgesics with different mechanisms of action. The objective of this study was to assess the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol compared with placebo in females experiencing moderate-to-severe pain due to primary dysmenorrhoea, a prevalent, recurrent condition characterised by pain at the time of menses.

Methods:

This was a phase II/III, double-blind, randomised, cross-over, single-dose study in 94 women with moderate-to-severe dysmenorrhoea, examining the efficacy and tolerability of one or two tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg compared with placebo.

Clinical trial registration:

ISRCTN42521357

Results:

Total pain relief over 6 hours post-dose (TOTPAR_0–6h) was significantly greater following administration of two tablets of the single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg compared with placebo (LS means: 2.35, 1.85, respectively; p = 0.0001) and approached significance for one tablet (LS mean: 2.10; p = 0.054). Statistically superior pain relief and reductions in pain intensity were achieved from 2 hours and 90 minutes post-dose, respectively, with the higher dose combination, and from 4 hours with the lower dose combination compared with placebo. Overall effectiveness (sum of pain intensity difference and pain relief score [SPRID] over 6 hours) were statistically superior to placebo for both one and two tablets of the ibuprofen/paracetamol combination (p = 0.0011 and p = 0.03, respectively). Both dose combinations were well-tolerated. Adverse events were minor and their frequency and nature did not differ with either treatment compared with placebo.

Conclusions:

One or two tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg is well-tolerated and provides superior analgesic efficacy to placebo in patients with primary dysmenorrhoea.

Key words:

• Analgesia
• Ibuprofen
• Paracetamol
• Dysmenorrhoea
• Period pain

Transparency

Declaration of funding

This study was sponsored by Reckitt Benckiser Healthcare International Ltd.

Declaration of financial/other relationships

R.E. and M.J. acted as investigators for the clinical trial but did not receive any payment above their normal university salary for this role and did not receive any other payment from the sponsor for advice on this publication. They have no financial or other interests in the trial and its outcome. A.H. is an employee of Reckitt Benckiser Healthcare International Ltd. Peer reviewers may receive honoraria for their review work on CMRO. Peer Reviewer 1 has disclosed that he/she is a recipient of sponsorship funding from Novalar and Septodont; is a recipient of research/grant funding from Church and Dwight and Wyeth; is a consultant to Novalar and Ortho McNeil; and is a participant in a dividend reinvestment plan with Merck & Co. Inc. Peer Reviewer 2 has disclosed no relevant financial relationships.

Acknowledgements

The authors would like to thank Mike Goulder, Iain Gibb, and Suhair Jawad for their invaluable contribution to this study. Editorial assistance for the development of this article was provided by Elements Communications, supported by Reckitt Benckiser Healthcare Ltd.