Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

Abstract

Background: To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity.

Methods: This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests.

Results: At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups.

Conclusions: This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity.

Clinical trial registration: ClinicalTrials.gov: NCT01656668.

Keywords: Cocoa; controlled clinical trial; cough; quality of life (QOL); theobromine.

Conflict of interest statement

Conflicts of Interest: AH Morice was chief investigator of this study. He has received speaker’s honoraria from Astra Zeneca, Chiesi, Boehringer Ingelheim, Almirall, and Novartis. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, Astra Zeneca and Chiesi. L McGarvey was an investigator in this study, which was funded by Infirst Healthcare. ID Pavord has received speaker’s honoraria in the last 5 years for speaking at sponsored meetings from Astra Zeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, and GSK and payment for organising an educational event from Astra Zeneca. He has received honoraria for attending advisory panels with Almirall, Genentech, Regeneron, Astra Zeneca, Boehringer Ingelheim, GSK, MSD, Schering-Plough, Novartis, Dey, Napp and Respivert. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, Astra Zeneca and Napp. B Higgins was an investigator in this study, which was funded by Infirst Healthcare. KF Chung was an investigator in this study, which was funded by Infirst Healthcare. SS Birring has received personal fees from Infirst Ltd for scientific advisory boards and advice.

Figures

Figure 1

CONSORT flow diagram. LCQ, Leicester Cough Questionnaire.

Figure 2

Effect of theobromine versus placebo on the change in mean (standard deviation) Leicester Cough Questionnaire (LCQ) scores.