A CARAWAY OIL/MENTHOL COMBINATION IMPROVES FUNCTIONAL DYSPEPSIA (FD) SYMPTOMS WITHIN THE FIRST 24 HOURS: RESULTS OF A RANDOMIZED CONTROLLED TRIAL, WHICH ALLOWED USUAL FD TREATMENTS
Brian E. Lacy, William D. Chey, Brooks D. Cash, Michael Epstein, Syed M. Shah
Background: Functional dyspepsia (FD) is common, and there is no FDA approved medication for the treatment of FD. FD is subcategorized as postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS), and meal ingestion triggers the generation of symptoms in many patients. The severity of PDS symptoms peaks within 50 minutes, while the severity of EPS symptoms peaks within 75 minutes after a meal. A rapid acting treatment that improves FD symptoms within 24 hours would be welcomed by providers and patients. An enteric-coated capsule containing a combination of caraway oil and peppermint oil (principal active L-menthol) has been evaluated successfully in several RCTs for FD. A single capsule containing 25 mg of caraway oil and 20.75 mg of L-menthol (COLM) was developed as microspheres ~1 mm diameter so that they may readily pass the pylorus and exert an effect during the first migrating motor complex after administration. The FDREST trial was performed to assess the effect, within 24 hours of administration, of COLM vs placebo for FD symptoms. Importantly, the protocol allowed concomitant medicines to be used for FD to mimic real-world practice.
Methods: One-hundred subjects were enrolled at 9 sites, all of whom met Rome III criteria for FD. Subjects who reported at least moderate symptoms (≥4 points on either question of the 7-point GOS scale) on at least 4 days during the 14- day screening period were randomized. Subjects took two capsules of COLM or matching placebo in the morning and at dinner time. In this trial, COLM was added concomitantly to previously individualized drugs (PPIs, H2RAs, anticonvulsants, beta blockers, antihistamines, antidepressants/TCAs, anti-nociceptive agents, and antacids). Study patients were subcategorized into PDS or EPS predominant based on symptoms. This study examined self-reported Global Overall Symptoms (GOS) of FD in patients given COLM versus a placebo group at 24 hours. Results: At 24 hours, the COLM arm demonstrated a statistically significant (P= 0.0393) reduction of PDS symptoms (Figure 1) while also improving EPS symptoms (P= 0.0764; Figure 2) in the overall population. In the PDS subcategory, the COLM arm demonstrated statistically significant reduction of both PDS (P=0.0225) and EPS symptoms (P= 0.0121) at 24 hours. In the EPS subcategory, the COLM arm demonstrated statistically significant reduction of both EPS (P=0.0028) and PDS symptoms (P=0.0186) at 24 hours.
Conclusion: In FD, an area of high unmet medical need, a novel COLM formulation provided significant symptom relief at 24 hours in both EPS and PDS patients. To our knowledge, this is the first time that a product has shown rapid relief of FD symptoms, even when used as an add-on therapy.