The products tested were Cyclavance® 100 mg/ml oral solution (Virbac, France) and Atopica® 50 mg or Atopica® 100 mg capsules (Novartis Animal Health, Switzerland). The products were administered orally.
The studies were carried out in accordance with the relevant European legislation and Virbac’s chart of Ethics (Study 1: EU-2014/11-13; Study 2: CE VB-2012-25-001).
Sixty adult healthy dogs, 32 females and 28 males, were included. The breeds represented included various unspecified mixed breeds (58%), Beagle (20%), Fox Terrier (8%), Spaniel (5%), Cocker Spaniel (3%), Jack Russel Terrier, Shetland Sheepdog, and Schnauzer (less than 2% each). The dogs were aged between 1.5 and 16.2 years with a mean age of 7.3 (±3.3) years and weighed between 7.7 and 23.8 kg with a mean weight of 13.6 (±4.0) kg. Animals were housed, managed and fed as normal and no alteration was required for the purpose of the study. Water was given ad libitum. The dogs were fed once per day with a complete dry maintenance food for adult dogs at 8 am each day.
This mono-center, controlled, randomised cross-over study was conducted in accordance with the rules of the European Union on Animal welfare in a specialised kennel. Given the obvious difference between the formulations (oral solution vs capsule) of the two tested products, the palatability tests could not be blinded. At enrolment the animals were divided into three groups consisting of twenty dogs each according to their bodyweight (≤10 kg, 10–14.9 kg, ≥15 kg). Dogs were then randomly allocated within each group to Sequence A or Sequence B in a tiered fashion based on their sex and age. The testing consisted of two sequences of three days of product administration separated by two days of wash-out. Sequence A consisted of Atopica® for three days, followed by two days of wash-out, then Cyclavance® for three days. Sequence B consisted of Cyclavance® for three days, followed by two days of wash-out, then Atopica® for three days.
The prehension and consumption of Cyclavance® was compared with that of Atopica® by the means of acceptance tests. These started at 2 pm on each study day. The dogs received 0.05 ml/kg of Cyclavance® or one capsule of Atopica® mixed with 30 grams of dry food presented in a bowl (Cyclavance® was poured onto the kibbles and the whole capsule of Atopica® was buried in kibbles). According to label recommendation, the dogs weighing between 7.5 and 15 kg were administered Atopica® 50 mg and the dogs weighing between 15 and 29 kg were presented with Atopica® 100 mg. The bowl containing the food and product was positioned on the floor inside the animal’s pen. A timer was started when the dog was allowed access to the bowl and was stopped when the product entered the animal’s mouth. The time to take the product was recorded as less than 2 seconds or more than 2 seconds. If after 60 seconds, the product had not been taken into the mouth, the test was terminated and the prehension was assessed as “no intake”. Each time kibbles or the capsule were prehended, the dog was observed during a further 5 minutes in order to register if it swallowed the product or if it spat it out. The amount of liquid and food remaining in the bowl were also recorded.
Classification of product prehension and consumption
Prehension was defined as the animal voluntarily taking the product into the mouth. The prehension of the tested products was further classified as immediate (less than 2 seconds), delayed (more than 2 seconds), or no prehension. Product and kibble consumption was classified as total (100%), partial, and none (0%).
The dogs were monitored closely throughout the study with a requirement for any abnormal events to be recorded in the individual clinical report form of each dog.
Twenty adult healthy Beagle dogs, 12 females and 8 males, were enrolled. The dogs were aged between 0.5 and 3.2 years with a mean age of 2.2 (±0.8) years and weighed between 9.6 and 14.2 kg with a mean weight of 11.6 (±1.5) kg. Water was given ad libitum. The dogs were fed once per day with a complete dry maintenance food for adult dogs and housed in individual pens.
Study design and test procedure
For this mono-center, controlled, randomised study the animals were randomly allocated to receive Cyclavance® or Atopica® in a tiered fashion according to their bodyweight and sex. The products were administered once per day during the 14-day study period at least 2 hours before meal time. In the Cyclavance® group the dosage was progressively increased from 1 to 4 mg/kg over a four-day period (from D0 to D3) then 5 mg/kg were administered daily over the ten remaining days (from D4 to D13). In the Atopica® group one capsule of Atopica® 50 mg was administered daily to all dogs as per the label recommendations. As a result, the dosage of ciclosporin given in this group varied between 3.5 and 5.2 mg/kg depending on bodyweight.
Classification of product voluntary acceptance and consumption
Cyclavance® was administered directly in the dog’s mouth with the syringe. Atopica® capsules were offered by the hand and if not taken within 1 minute were inserted into the mouth.
The product intake was classified as voluntary acceptance (Syringe easily inserted into the mouth or capsule taken from the hand of the technician, combined with willingness to swallow the product) or forced administration (need for a strong animal handling to insert the syringe into the dog’s mouth or need to insert the capsule at the back of the throat or need for restraint to ensure swallowing).
A clinical examination of each dog including stool appearance, appetite and overall condition was performed before the beginning of the test procedure (on D0) and on each study day. Photographs of the faecal matter were taken each morning. Fecal scores were then blindly assessed at study completion by two different operators for each dog on each study day using a previously-validated scoring chart (scores 0–5) . Furthermore, all dogs were weighed on D0, D7 and D14 and fasting blood samples were taken on D0 and D14 for haematology and biochemistry analysis. The number of dogs showing at least one gastrointestinal event (vomiting and/or diarrhoea) occurring over the first 4 study days and during the course of the entire study was compared between product groups.
Statistical analyses were performed using SAS 9.3. In study 1, product prehension, product consumption and food consumption were compared between products using a general linear model (Proc GLM in SAS) for crossover study, with sequence, dog (sequence), product, period and product*period as fixed effects. This model was used to show if there was a relation or not between the product prehension, the product consumption, the food consumption, and the product, taking into account the period and the sequence.
In study 2, product acceptance was compared between products using a generalized linear model for repeated measures (Proc GENMOD in SAS), with group and day as fixed effects. This model was used to show if there was a relation or not between the product acceptance and the product, taking into account the repeatability of the measures (once per day, during 14 days).
The significance threshold was set at 5% for both studies.