GHX02

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non‐clinical safety testing comprised a single‐dose oral toxicity study and a 28‐day repeated‐dose oral toxicity study with a 14‐day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single‐dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28‐day repeated‐dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single‐dose study. The no‐observed‐adverse‐effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague‐Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

Acute bronchitis is a self-limiting infection of the large airways; cough is the primary symptom, usually lasting for about 3 weeks. Annually, approximately 5% of adults develop acute bronchitis, and its economic burden is substantial. There are also problems of antibiotic abuse in public health systems and symptomatic therapies are commonly prescribed, for which there is insufficient supporting evidence. GHX02 contains four herbs originating from gwaruhaengryeon-hwan, which has been used in the treatment of patients with acute bronchitis in Korea. The objective is to compare the GHX02 and placebo in terms of efficacy and safety, and to determine the appropriate dosage.

We planned a phase II, multicentre, dose-finding, double-blind, randomised placebo-controlled trial of two different doses of GHX02 compared with placebo. A total of 150 patients, aged 19–75 years, with a Bronchitis Severity Score (BSS) ≥5 due to acute bronchitis starting within 2 weeks of study enrolment will be recruited from three university-affiliated hospitals across Korea. Participants will be stratified into three patterns using the Korean Standard Tool of Pattern Identifications of Cough and Sputum and randomly assigned to either a high-dose GHX02 group (1920 mg/day), standard-dose GHX02 group (960 mg/day) or placebo group according to a 1:1:1 allocation ratio. Patients will take medications three times daily for 7 days, with two visiting days. The primary outcome measure is a change in BSS from day 0 to day 7. The secondary outcomes are the Questionnaire of Clinical Symptoms of Cough and Sputum, Leicester Cough Questionnaire, frequency of coughing fits, Integrative Medicine Outcome Scale, Integrative Medicine Patient Satisfaction Scale and withdrawal rate of patients with exacerbation. Safety will be assessed by adverse events, vital signs and laboratory examinations.

The study has been approved by our Institutional Review Board (No. DJDSKH-17-DR-14). The trial results will be disseminated via peer-reviewed journals and the Clinical Research Information Service.

NCT03310385; Pre-results.