Infirst Healthcare (United Kingdom)

IntroductionCS1002 contains diphenhydramine/ammonium-chloride/levomenthol in a demulcent preparation. We conducted a randomised controlled trial to compare the efficacy of CS1002 with Bell’s Simple Linctus (BSL).Methods163 subjects with acute cough associated with upper respiratory tract infection, URTI (onset ≤7 days and cough severity VAS ≥60 mm), presenting to pharmacists (64%) or general practitioners were randomised to CS1002 or BSL. The subjects (mean age 39 years, 57% female) were instructed to take their medication four times daily (5/5/10/10 ml) for 7 days or until resolution. Investigators were blinded to the treatment allocation. The primary analysis, cough severity VAS (0–100) was ANCOVA in an intention to treat population.ResultsCS1002 (n = 82) compared to BSL (n = 75), after 3 days, was associated with a greater reduction in cough severity (adjusted mean(SE) difference 5.9 (4.3), p = 0.18), cough sleep disruption VAS (mean diff 11.6 (4.5), p = 0.01) and cough frequency VAS (mean diff 8.1 (4.1), p = 0.05, Figure 1). There was a greater improvement in QOL (LCQ-acute) with CS1002 compared to BSL after 5 days; mean diff 1.2 (0.6), p = 0.04. The reduction in cough severity with CS1002 was similar in dry/chesty/tickly categories of cough. Cough resolved after 3 days in 24.4% of CS1002 subjects compared to 10.7% BSL, p = 0.02. CS1002 was well tolerated, similar to BSL.In conclusionWe have conducted the largest RCT in URTI with validated outcome measures. CS1002 reduced the impact of cough associated with URTI with a greater reduction in cough frequency and sleep disruption and improvement in QOL and cough resolution compared to BSL. S29 Figure 1Change in cough frequency over time (Full Analysis Set)

Background: Currently available over-the-counter cough remedies historically have been criticized for lack of scientific evidence supporting their efficacy. Although the first-generation antihistamine diphenhydramine is classified as an antitussive by the United States Food and Drug Administration, to the authors’ knowledge it has never been shown to inhibit cough reflex sensitivity in subjects with pathological cough. Objective: To evaluate the effect of diphenhydramine on cough reflex sensitivity. Setting: Montefiore Medical Center, an academic medical center in New York City. Methods: Twenty two subjects with acute viral upper respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on 3 separate days, 2 h after ingesting single doses of study drug (to coincide with peak blood concentrations), administered in randomized, double-blind manner: a multicomponent syrup containing diphenhydramine (25 mg), phenylephrine (10 mg), in a natural cocoa formulation; dextromethorphan (30 mg) syrup; and, placebo syrup. The standard endpoint of cough challenge was used: concentration of capsaicin inducing ≥5 coughs (C5). Main outcome measure: Effect on cough reflex sensitivity (C5). Results: A significant difference (p = 0.0024) was established among groups, with pairwise analysis revealing a significant increase in mean log C5 (0.4 ± 0.55 (SD); p < 0.01) for the diphenhydramine-containing medication versus placebo, but not for dextromethorphan versus placebo. Conclusions: Our results provide the initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough. Timing of cough reflex sensitivity measurement may not have allowed demonstration of maximal antitussive effect of dextromethorphan.