A single-dose, open-label, randomized, scintigraphic study to investigate the gastrointestinal behavior of 2 triple-combination cold products (acetaminophen, phenylephrine, and dextromethorphan) in healthy male volunteers

Abstract

Background: Common cold symptoms may be mitigated by products in caplet, nasal spray, and oral solution formulations, although variations exist in the bioavailability of the active ingredients contained within these products. Rapid gastric emptying (GE) of these active ingredients is important for reducing the delay between drug absorption and onset of cold symptom relief. Hot drink cold remedies are associated with greater comfort and may enhance the bioavailability of active ingredients. The objective of this study was to characterize the gastrointestinal transit of powder (reconstituted in hot water) and caplet formulations of commercially available multisymptom cold medications.

Methods: This was an open-label, single-dose, parallel-group study. Healthy male adults under fasted conditions were randomized 1:1 to receive a single dose of radiolabeled Theraflu Daytime Severe Cold and Cough powder for oral solution or radiolabeled Theraflu ExpressMax Daytime Severe Cold and Cough caplet. External gamma scintigraphy was utilized to monitor GE and intestinal transit of two radiolabeled drug formulations.

Results: A total of 28 participants completed the study. The mean ± SE GE onset times were 1.1 ± 0.3 min and 8.5 ± 1.8 min for powder and caplet formulations, respectively. The mean ± SE GE completion times were 121 ± 13 min and 65 ± 13 min, respectively. Despite the similar mean times to GE25%, the powder had later mean GE50% (23 ± 3.0 vs 16 ± 3.2 min, respectively) and GE90% (85 ± 12 vs 36 ± 9 min, respectively) than caplets. Caplets had a shorter overall GE half-life, lower total gastric exposure, and faster transit time through the small intestine versus the powder formulation. No serious safety events were observed.

Conclusion: The results of this study in healthy male adults suggest that the Theraflu powder formulation had a more rapid GE onset but longer time to GE completion than the caplet formulation.

Trial registration: ClinicalTrials.gov NCT03415243.

Keywords: Beverages; Common cold; Duodenum; Gamma scintigraphy; Gastric emptying; Powders; Radionuclide imaging.

Conflict of interest statement

PM is an employee of GSK Consumer Healthcare and is a stock shareholder in the company. MA is an employee of GSK Consumer Healthcare and is a stock shareholder in the company. WJD is an employee of Scintipharma, which was contracted by and received compensation from GSK Consumer Healthcare to conduct the clinical study. RCP is an employee of Scintipharma, which was contracted by and received compensation from GSK Consumer Healthcare to conduct the clinical study. EPS is an employee of Scintipharma, which was contracted by and received compensation from GSK Consumer Healthcare to conduct the clinical study.

© 2022. The Author(s).

Figures

Fig. 1

Study design. *Powder dissolved in hot water. aMedical history recorded was any existing or resolved condition that started prior to informed consent. Changes in the medical history were assessed at visit 2 (day 1). bFull physical examination occurred on visit 1 screening and on visit 2 (day − 1). A brief physical examination occurred on visit 2 (day 1) before randomization and prior to discharge. cVital signs performed at visit 1 and visit 2 (day − 1) included BP, RR, PR, and oral temperature. At visit 2 (day 1), vital signs included BP and PR performed before randomization and after the last scintigraphic image was obtained. dAEs (serious and non-serious) were collected from the time the subject signed the informed consent form until 5 days following the last administration of the investigational product. eSubjects were given a standard lunch 4 h post-dose and a standard dinner 10 h post-dose. fFasting occurred from 10 h prior until 4 h after study drug administration. gLaboratory tests on visit 2 (day 1) were conducted after the final scintigraphic image was taken, prior to dinner. eScintigraphic acquisitions were taken beginning after dose administration until 10 h post-dose. AEs, adverse events; BP, blood pressure; ECG, electrocardiogram; PR, pulse rate, RR, respiratory rate

Fig. 2

Participant disposition

Fig. 3

Mean time to GE onset (A) and completion (B) post-ingestion (scintigraphy analysis population). GE, gastric emptying; SE, standard error

Fig. 4

Mean time to 25%, 50%, and 90% GE post-ingestion (scintigraphy analysis population). GE, gastric emptying; SE, standard error

Fig. 5

Mean post-ingestion 99mTc DTPA stomach levels over time (scintigraphy analysis population). A Amount remaining. B Sectional areas under the GE curve. 99mTc DTPA, technetium-99m diethylenetriaminepentaacetic acid; GE, gastric emptying; SE, standard error; t½, terminal half-life