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1852 Zollers et al

to Good Clinical Practices (Food and Drug Administration behavior of their dog when anticipating meal time, the behavior
(FDA) Center for Veterinary Medicine (CVM) Guidance 85; when food was placed in front of their dog, and the amount of
VICH GL 9). food eaten. Each question could be scored from 1 to 5 with 5 indi-
cating the best appetite. Scores for each dog were given as a total
score (range of 5–25).
Animals/Subjects
Because assessment of appetite during the study might be
Dogs of any age, breed, or sex were enrolled, but dogs that confounded by offering the enrolled dogs highly palatable food
were pregnant, lactating, or intended for breeding were excluded. that was not in their normal diet before the study, owners were
asked not to entice or tempt their dog to eat during the study
Each owner signed a statement of informed consent before the ini-
using treats or highly palatable food that they did not normally
tiation of any study activities.
give their dog. To document this, each owner was asked to
record all foods they gave their dogs, including any special
Inclusion/Exclusion Criteria foods or treats to encourage eating during the previous 2 days
when their dog was experiencing inappetence. This was defined
Client-owned dogs that were presented by the owner with
as the base diet. The owner was then instructed to only offer
clinical signs of either a reduced appetite or no appetite for a
their dog foods on the base diet during the 4 days of the study.
minimum of 2 days before presentation were candidates for Owners were asked to record all the foods that were offered
enrollment. The owner was asked to answer the following ques- during the study, and the veterinarian reviewed this listing of
tion as it best described their dog’s appetite at screening: “Do foods to assure that the owners had not fed foods that deviated
you feel that your dog’s appetite today compared to when it from the base diet.
was at its healthiest adult stage is increased, no change, or
decreased?” If the owner’s response was “decreased,” the dog
could be enrolled. Dogs that were in crisis or a moribund state, Randomization and Masking
or dogs with a serious deteriorating condition were excluded, as
were dogs that had been hospitalized within the 4 days before After enrollment, dogs were randomly assigned to the
presentation. Also excluded were dogs with an active infection capromorelin or placebo group in a 2 : 1 ratio. The enrollment
that would likely respond to treatment with an antibiotic, and target was at least 100 capromorelin and 50 placebo-treated
dogs in which food intake was contraindicated such as a sus- evaluable cases per the study randomization schedule across all
pected foreign body or gastric torsion. Dogs with a regurgita- sites.
tion problem, dental disease severe enough to impair food Dogs were randomly assigned to 1 of 3 treatment codes
intake, and any dog with a diagnosis of diabetes mellitus were based on order of entry into the study, by a randomization
excluded. Dogs were not enrolled if the owner was unsure if table provided by the study statistician. The program used to
Ò
e
they could reliably evaluate appetite. Medications that might randomly assign treatments to dogs was SAS Proc Plan. Each
affect appetite or interfere with the study objectives such as ana- site had a unique randomization schedule. Treatments were
bolic steroids, diazepam, dronabinol, cyproheptadine, mirtazap- labeled as “Treatment A,” “Treatment B,” or “Treatment C”
ine, propranolol, progesterone, and systemic corticosteroids with 2 of the labeled treatments being capromorelin and 1 of
(within the last 30 days) were not allowed. Maropitant citrate b the labeled treatments being placebo to maintain a 2 : 1 ratio.
was allowed during the study if prescribed before study start, A note to file identifying capromorelin or placebo assignment to
and the treatment was stable. No parenteral fluids could be treatment codes A, B, and C was created by a contract
administered within approximately 12 hours of the last study research group employee not involved in the study and main-
visit on day 3 1, as fluid administration might affect the body tained in the central files for the duration of the study. To
weight measurement. maintain masking, this note to file was not accessible to any
other personnel involved in the study until the database was
locked.
Sample Size Calculation
7
Based on data from a pilot clinical study in which 70.6% of Treatment
capromorelin-treated dogs and 38.5% of the placebo-treated dogs
were considered a treatment success (increased appetite); a power Day 0 was the first day of treatment. Each dog was treated
c
calculation by PASS 11 indicated that a sample size of 100 capro- once daily for 4 1 days with either placebo or capromorelin
morelin-treated dogs and 50 placebo-treated dogs with evaluable dosed orally at 3 mg/kg with a syringe provided with the study
cases would provide more than 97% power (alpha = 0.05, 2-sided) drug. Placebo flavored solution was matched to the capromorelin
to detect a difference in the proportion of treatment success flavored solution, including bottle size and shape, but without the
between groups. active drug. Owners were instructed to give the dose at approxi-
mately the same time each day. Compliance with dosing was eval-
Study Protocol uated by reconciling the returned study drug with what was
dispensed and supported by a daily owner diary indicating admin-
At screening, owners signed an informed consent form that had istration of the dose.
been approved by the Center for Veterinary Medicine (CVM) at
the FDA. This consent was signed before initiating any study
activities. Dogs were screened to see whether they met the inclu- Outcome Measures
sion and exclusion criteria, body weight was measured, blood was
Appetite over the 4 days was evaluated by the owners answer-
drawn to evaluate standard serum chemistry and hematology vari-
ing this question on day 3 1: “Do you feel that during the study
ables, and urine collected for urinalysis. At the screening visit, (over the 4 1 days of treatment), your dog’s appetite was
owners were asked to complete an Owner Appetite Assessment. d
increased, no change, or decreased?” If the owner answered that
This questionnaire consisted of 5 questions asking owners about
their dog’s appetite was increased, the dog was considered a treat-
their dog’s willingness to eat, hunger and begging behavior, the
ment success. To support this assessment of appetite, the owner