William D. Chey, Brian E. Lacy, Brooks D. Cash, Michael Epstein, Syed M. Shah
Background: There are no FDA-approved pharmaceutical agents for functional dyspepsia (FD). Previous trials suggested that a combination of caraway oil and peppermint oil (Lmenthol) may be effective for FD. The FD Reduction Evaluation and Safety Trial (FDREST) compared the effects of a single capsule containing caraway oil and L-menthol (COLM) formulated to allow targeted gastrointestinal delivery to placebo in FD patients taking their usual medications.
Methods: FDREST was a post-marketing, parallel group study that compared the efficacy and tolerability of COLM plus usual medications vs. placebo plus usual medications. Eligible patients met Rome III criteria for FD and reported at least moderate symptoms (≥ 4 points on a 7-point Global Overall Symptom [GOS] scale) on ≥ 4 days during a 14-day screening period. Patients with post-prandial distress and epigastric pain syndrome were included and analyzed both individually and as a single group. Each capsule of COLM contains 25 mg of caraway oil and 20.75 mg of L-menthol. Subjects took two capsules of COLM or matching placebo in the morning and at dinner time, 30 to 60 minutes before a meal, with a glass of water. The study examined changes in GOS and Clinical Global Impressions (CGI) as well as safety plus and tolerability over a treatment period of 28 days. In FDREST, COLM or placebo was added to each patient’s existing FD medication regimen (PPIs, H2RAs, anticonvulsants, beta blockers, antihistamines, antidepressants/TCAs, pain modulators, and antacids). Patients using medicines such as antiemetics, prokinetics, cholinergics, antidiarrheals, sedative hypnotics, NSAIDs, narcotic analgesics, oral heartburn and gas relief agents, probiotics, and antispasmodics had to complete a 14- day washout. 48 hours after the first dose, they were allowed to use these medicines after discussion and approval by the medical monitor.
Results: One-hundred patients were enrolled at 9 sites. The COLM arm showed reduction of symptoms at the 2-14 day and 15- 28 day evaluation points and was numerically superior to the active control arm for all measures (Figure 1). At end of treatment, 61% of patients given COLM reported either a “much” or “very much” improved assessment of CGI compared to 49% in the control group (P=0.23; Figure 2). There were no serious treatment-emergent adverse events (TEAEs) observed with COLM. The number of subjects with any TEAE in the COLM (12%) arm was less than control (15.6%) arm, as was the number of subjects with gastrointestinal (GI) events with COLM (12%) compared to the control arm (17.8%). Only 3 individual GI events (abdominal pain, nausea, and dyspepsia) were reported by > 4% of subjects, and all 3 were in the control arm. Conclusion: COLM is safe and effective at improving FD symptoms in patients already using commonly available medications for functional dyspepsia.