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Capromorelin for Appetite Stimulation in Dogs 1855

Safety phosphorus were slightly greater in the capromorelin
group as compared to the placebo group, but these dif-
The safety (ITT) population consisted of 171 dogs ferences were not significant.
treated with capromorelin and 73 dogs treated with pla-
cebo. Capromorelin was generally well tolerated. Nine
dogs experienced serious adverse events, 2 in the pla- Discussion
cebo group and 7 in the capromorelin group. The vet- This study indicates that a ghrelin receptor agonist,
erinarians did not attribute any of these serious adverse capromorelin, can stimulate appetite and increase body
events to treatment with capromorelin, but instead to a weight when given to a large population of dogs with
variety of preexisting conditions including heartworm reduced appetite of varying etiologies. The results estab-
disease, intestinal neoplasia, neurologic disease, hepatic lish that owners can evaluate relative changes in their
disease, and renal disease. dog’s appetite, using either a single simple question or
Frequencies of adverse events potentially related to an assessment questionnaire of the dog’s behavior.
treatment (adverse reactions) are given in Table 2. Increased appetite (hunger) is reflected in behaviors that
There were no adverse events in clinical pathology vari- owners can observe, which can be broadly defined as
ables except for values of blood urea nitrogen (BUN), how much a dog eats, how rapidly a dog eats, and how
creatinine, and phosphorus (Table 2). These adverse aggressively a dog seeks out food. The 5 questions on
event reports were in separate dogs, except for 1 capro- the Owner Appetite Assessment were designed to help
morelin-treated dog which experienced adverse events owners rate these behaviors. Although shown to be use-
for both increased BUN and increased phosphorus. ful in distinguishing between placebo- and capromore-
To further explore changes in BUN, creatinine, and lin-treated dogs in this study, additional work is
phosphorus in dogs in this study, these values were ana- required to formally validate this questionnaire.
lyzed for the safety population (Table 3). The mean As in other measurements where owners are asked to
change in BUN was slightly decreased in the capro- assess a clinical condition in their dogs, such as pain
morelin group and slightly increased in the placebo assessed by the Canine Brief Pain Inventory, This study
8
group, a difference that was statistically significant demonstrates a large placebo effect, with over 44% of
(P = .006), but because these changes were small, they owners saying their placebo-treated dog had an increased
were unlikely to be of clinical relevance. The mean appetite using the single question and 37.6% when using
change for creatinine was similar between groups and the Owner Appetite Assessment questionnaire. Some of
the mean change in phosphorus was small and positive these placebo-treated dogs might have legitimately had
for both groups, with the placebo group exhibiting a an increased appetite due to spontaneous improvement
larger mean increase. in the underlying cause of inappetence, but it is not
Given that increases in BUN, creatinine, and phos- unexpected to see a large placebo effect in an owner
phorus can be associated with renal disease, changes in assessment in studies with client-owned dogs. The single
these variables were also evaluated for dogs which at question did not seem to be as robust (success difference
screening satisfied the International Renal Interest Soci- of 24% between groups) in assessing appetite changes as
ety (IRIS) staging guidelines for chronic kidney disease the Owner Appetite Assessment, which gave owners a
stage ≥2 (creatinine ≥1.4 mg/dL, regardless of the labo- more nuanced set of questions to answer (success differ-
ratory’s reference interval). Mean changes in BUN from ence of 35.7% between groups).
day 0 to day 3 1 were similar between groups Given the short duration of this study, changes in
(Table 4). The mean changes in creatinine and body weight were expected to be small. Even in such a
short period of time, the capromorelin-treated group
experienced a larger increase in body weight as com-
Table 2. Adverse reactions in dogs treated with either pared to the placebo-treated group. Additionally, a lar-
placebo or capromorelin for 4 days (safety population).
ger proportion of dogs in the capromorelin-treated
group exhibited a change in body weight of >0%. These
Capromorelin Placebo
(N = 171) (N = 73) results are consistent with capromorelin stimulation of
Adverse reactions * N (%) N (%) appetite resulting in increased contents of the gastroin-
testinal tract, both food and water. One of the actions
Diarrhea 12 (7.0%) 5 (6.8%) 6
Vomiting 11 (6.4%) 4 (5.5%) of capromorelin is to stimulate an increase in GH,
Increased blood urea nitrogen 7 (4.1%) 2 (2.7%) which can result in an increase in lean muscle mass, but
Polydipsia 7 (4.1%) 1 (1.4%) it is unlikely that dogs gained muscle mass during such
Increased phosphorus 4 (2.3%) 1 (1.4%) a short study. Future studies will be needed to investi-
Hypersalivation 4 (2.3%) 0 (0.0%) gate the effects of long-term administration of capro-
Abdominal discomfort 2 (1.2%) 0 (0.0%) morelin oral solution on body weight and lean muscle
Flatulence 2 (1.2%) 0 (0.0%) mass in client-owned dogs.
Lethargy/depression 2 (1.2%) 0 (0.0%)
Care was taken in the study to not confound the
Nausea 2 (1.2%) 0 (0.0%)
results by offering or enticing the dogs with particularly
Increased creatinine 1 (0.6%) 1 (1.4%)
palatable food, which would make assessing the appetite
*Dogs might have experienced more than one type or occur- difficult. If foods were consumed that were not listed on
rence during the study. the base diet, then those cases were considered to be