Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

Abstract

Yong Yue,1 Kenneth D Reed,1 Lucy Shneyer,2 Dongzhou J Liu3 1GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, 2Shneyer Statistics LLC, Denville, NJ, 3GlaxoSmithKline, Collegeville, PA, USA Objectives: Two randomized placebo-controlled trials evaluated whether combining rapid-acting paracetamol formulations with caffeine resulted in faster/greater relief of episodic tension-type headache (ETTH) compared with placebo and over-the-counter (OTC) analgesics. Both studies were prematurely terminated. Materials and methods: In the single-blind crossover study 1, adults with ETTH (n=66) received three of the following in random sequence: paracetamol 1,000 mg with sodium bicarbonate 650 mg and caffeine 130 mg; paracetamol 1,000 mg; ibuprofen 400 mg; and placebo. In the double-blind parallel-group study 2, adults with ETTH (n=157) were randomly assigned 2:2:1 to treat up to three headaches with paracetamol with Optizorb technology 1,000 mg plus caffeine 130 mg; ibuprofen 400 mg; and placebo. Results: In study 1, the primary outcome – mean time to perceptible pain relief – was 36.7, 38, 48.9, and 42.7 minutes in the paracetamol–sodium bicarbonate–caffeine, ibuprofen, paracetamol, and placebo groups, respectively; differences were not statistically significant. In study 2, the weighted sum of pain intensity (scale of 0 [no pain] to 4 [severe pain]) difference from the time of treatment to hour 4, the primary outcome, showed numerically favorable differences for paracetamol with Optizorb–caffeine compared with ibuprofen (difference in least square means −0.3, 95% confidence interval −1.05 to 0.45) and placebo (−0.47, 95% confidence interval −1.36 to 0.42). In both studies, secondary outcomes suggested faster and greater relief with rapid paracetamol–caffeine compared with placebo and paracetamol; a few of these outcomes achieved statistical significance at ~45–90 minutes in study 1. Adverse events were mostly mild and consistent with known safety profiles of OTC analgesics and caffeine. Conclusion: Firm conclusions regarding the speed and efficacy of rapid-acting paracetamol formulations plus caffeine compared with placebo and traditional OTC analgesics for ETTH cannot be drawn, because the studies were terminated early. Some encouraging trends seen suggest this combination deserves further investigation. Keywords: paracetamol, caffeine, ibuprofen, tension-type headache, pain

Keywords

• paracetamol
• caffeine
• ibuprofen
• tension-type headache
• pain