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Standard Article
J Vet Intern Med 2016;30:1851–1857

A Prospective, Randomized, Masked, Placebo-Controlled Clinical
Study of Capromorelin in Dogs with Reduced Appetite

B. Zollers, J.A. Wofford, E. Heinen, M. Huebner, and L. Rhodes

Background: Reduced appetite is a common clinical sign in dogs. This study evaluated the effectiveness and safety of
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capromorelin oral solution, (ENTYCE , Aratana Therapeutics, Leawood, KS) a new drug that is a ghrelin receptor agonist,
for stimulation of appetite in dogs with reduced appetite.
Hypothesis/Objectives: Capromorelin will increase appetite, as measured by the owner’s evaluation, over 4 days. An addi-
tional objective was to evaluate the safety of capromorelin at the labeled dose.
Animals: A total of 244 client-owned dogs reported by owners to be inappetent for at least 2 days were enrolled, with
177 cases in the effectiveness analysis.
Methods: In this prospective, randomized, masked, placebo-controlled study, dogs were treated daily with capromorelin
(3 mg/kg) oral solution (n = 121) or placebo oral solution (n = 56). Owners completed an evaluation of appetite at days 0
and 3 1. Success was defined as improvement in appetite at day 3. Safety was evaluated by physical examination, clinical
pathology, and monitoring adverse events and owner observations.
Results: Capromorelin treatment improved appetite compared to placebo (68.6% and 44.6% treatment successes with
95% CI 59.7, 76.3 and 32.2, 57.8, respectively, P = .008). Mean body weight in capromorelin-treated dogs increased com-
pared to placebo-treated dogs (1.8% with 95% CI 1.3, 2.3, and 0.1% with 95% CI 0.9, 1.1, respectively, P < .001). Adverse
reactions occurring in >5% of either group were diarrhea and vomiting.
Conclusions and Clinical Importance: Capromorelin oral solution is an effective treatment for stimulation of appetite in
dogs and represents the first ghrelin receptor agonist shown to be effective for this indication.
Key words: Appetite stimulation; Food consumption; Ghrelin receptor agonist; Growth hormone secretagogue;
Inappetence.

rowth hormone secretagogues (GHS) are a class of Abbreviations:
Gsmall molecule compounds discovered in the mid- BUN blood urea nitrogen
1990s that bind GHS receptors (GHS-R) and stimulate CI confidence interval
the release of growth hormone (GH). It was subse- CVM Center for Veterinary Medicine
quently discovered that GHS compounds mimic ghre- FDA Food and Drug Administration
lin, the hormone that is secreted from endocrine cells GH growth hormone
in the stomach and stimulates appetite and food intake GHS growth hormone secretagogue
in humans, rats, and dogs. 1,2 A GHS compound is GHS-R growth hormone secretagogue receptor
therefore also called a ghrelin receptor agonist. Com- IRIS International Renal Interest Society
pounds in this class could be useful in treatment of ITT intention to treat
anorexia and cachexia, 3 and one compound in this PPP per protocol population
SD standard deviation
class has been evaluated for its ability to increase body
weight and lean muscle mass in human patients with
cancer cachexia. 4
Capromorelin is an orally active small molecule stimulation of appetite in dogs. We hypothesized that
GHS that is a potent and selective ghrelin receptor dogs presented at veterinary clinics with a reduced
agonist. 5 (Note: Capromorelin is also referred to as appetite and treated with capromorelin would have
AT-002 and CP-424,391). The compound has been for- increased appetite and, subsequently, body weight.
a
mulated in a flavored solution and approved by the Capromorelin increases food consumption and body
6
Food and Drug Administration (FDA) for the weight in laboratory Beagle dogs and appetite and 7
body weight in client-owned dogs with inappetence.
The purpose of this study was to examine the appe-
tite-stimulating effect of capromorelin oral solution
From Aratana Therapeutics, Leawood, KS (Zollers, Wofford, compared to placebo oral solution in a larger popula-
Heinen, Rhodes); ClinData Services, Fort Collins, CO (Huebner). tion of client-owned dogs, as well as document the
Corresponding author: Jessica A. Wofford, Aratana Therapeutics,
11400 Tomahawk Creek Pkwy, Suite 340, Leawood, KS 66211; safety of the drug in this population.
e-mail: jwofford@aratana.com
Submitted March 25, 2016; Revised August 2, 2016; Materials and Methods
Accepted September 29, 2016.
Copyright © 2016 The Authors. Journal of Veterinary Internal Study Design
Medicine published by Wiley Periodicals, Inc. on behalf of the Ameri-
can College of Veterinary Internal Medicine. The study was a prospective, multicenter, masked, randomized,
This is an open access article under the terms of the Creative placebo-controlled parallel study conducted at 24 veterinary hospi-
Commons Attribution-NonCommercial License, which permits use, tals located across the United States (California, Colorado, Flor-
distribution and reproduction in any medium, provided the original ida, Illinois, Kansas, Michigan, Missouri, Nebraska, New York,
work is properly cited and is not used for commercial purposes. Pennsylvania, Tennessee, and Texas). It was conducted according
DOI: 10.1111/jvim.14607