In a recent study, oral capromorelin was well tolerated and stimulated the appetite of inappetent dogs.
A prospective, multicenter study recently published in the Journal of Veterinary Internal Medicine reported on the safety and efficacy of oral capromorelin, an FDA-approved appetite stimulant for dogs.
Capromorelin is a growth hormone secretagogue (GHS), a class of small molecules developed to stimulate growth hormone release from the pituitary gland. In a previous study, GHS compounds were shown to function similarly to ghrelin, an appetite-stimulating hormone. Because GHS compounds mimic ghrelin’s activity, they are also known as ghrelin receptor agonists.
As a selective ghrelin receptor agonist, capromorelin has demonstrated efficacy in inappetent laboratory and pet dogs. Laboratory Beagle dogs with inappetence ate more and gained weight when given capromorelin. Similarly, inappetent pet dogs treated with capromorelin also demonstrated increased appetite and weight gain.
The current study was conducted at 24 veterinary hospitals across the United States. Dogs of any age, sex, or breed were enrolled if they had owner-reported inappetence for at least 2 days before the study (n=244). A known etiology of the inappetence was not required. All dogs were evaluated for safety and 177/244 were evaluated for efficacy.
Dogs were randomized 2:1 to receive once-daily oral capromorelin or placebo via syringe, administered by their owners. Two treatment groups received 3mg/kg capromorelin. The third treatment group received a flavored placebo solution. Study personnel and dog owners were masked to which treatments the dogs received.
On day 0, the first day of treatment, dog owners completed a 5-question Owner Appetite Assessment (OAA; developed by Aratana Therapeutics); each question was scored from 1 (worst appetite) to 5 (best appetite). Owners completed this same assessment on day 3±1.
For the 4-day study duration, owners fed their dog a strict base diet: the dog’s normal diet, including highly palatable food that had been given to stimulate appetite in the previous 2 days of inappetence. This base diet was necessary to prevent new, enticing food from being a confounding factor.
Authors defined success in two ways, the first of which was if they received an answer of “increased” to the following question on day 3±1: “Do you feel that during the study, your dog’s appetite was increased, no change, or decreased?” Using this definition, authors observed a significantly greater percentage of treatment success in dogs treated with capromorelin than placebo (68.6% vs 44.6%). The second definition of treatment success was an increase of 5 or more on the OAA from baseline (day 0) to day 3±1. Similarly, with this definition, a significantly greater percentage of treatment success was observed with capromorelin versus placebo (56.2% vs 26.8%).
From baseline to day 3±1, the mean percent change in OAA scores was significantly greater for capromorelin-treated dogs than placebo-treated dogs (73.3% vs 37.6%). For dogs with the worst appetites at baseline, the percentage of those with an increase of 5 or more on the OAA from baseline was significantly greater in the capromorelin treatment groups than the placebo treatment group (64.0% vs 27.1%).
All dogs gained weight during the study. The mean percent change in body weight was significantly greater with capromorelin than placebo (1.8% vs 0.1%). In addition, a significantly greater percentage of dogs gained weight with capromorelin than placebo (76.0% vs 44.6%).
In general, capromorelin was well-tolerated. The most common adverse events (AEs) were nausea and vomiting, which occurred with similar frequencies with capromorelin and placebo. Serious AEs were reported in 9 dogs, 7 of which were in the capromorelin treatment groups; authors attributed serious AEs to underlying medical conditions rather than capromorelin treatment.
From baseline to day 3±1, authors observed differences in mean changes in BUN, creatinine, and phosphorus values. BUN values decreased with capromorelin and increased with placebo; these mean changes were statistically significant, but small and not likely clinically relevant. Mean changes in creatinine values were similar between treatment groups. Phosphorus values increased from baseline with capromorelin and placebo; the mean change was greater with placebo, but was not statistically significant.
For dogs with stage ≥2 chronic kidney disease, according to International Renal Interest Society staging guidelines for chronic kidney disease (creatinine ≥1.4 mg/dL), mean changes in BUN, creatinine, and phosphorus values from baseline to day 3±1 were not statistically significant.
Authors noted the short study duration as a limitation. They suggested conducting studies “to investigate the effects of long-term administration of capromorelin oral solution on body weight and lean muscle mass in client-owned dogs.” A small population was also a limitation, not allowing for detection of rare AEs. Given the study’s positive findings, authors concluded that “capromorelin represents a promising new treatment modality for appetite stimulation in dogs.”
Authors acknowledged the AlcheraBio staff and other investigators.
Authors J.A. Wofford and E. Heinen are current Aratana Therapeutics employees; B. Zollers and L. Rhodes are former Aratana Therapeutics employees. All authors have Aratana Therapeutics stock, stock options, or both.
Dr. JoAnna Pendergrass received her doctorate in veterinary medicine from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, LLC.