A. Dose Establishment
No additional dose establishment work was required. The minimum target dose
of milbemycin oxime 0.5 mg/kg body weight was established in the original
NADA 140-915 for the currently approved label indications.
B.Dose Confirmation
One dose confirmation study (Trial AH-93-0045) was conducted to evaluate
the effectiveness of milbemycin oxime in the removal and control of the adult
roundworm, Toxascaris leonina. Twenty-four dogs were infected with
eggs of Toxascaris leonina by oral inoculation 75-77 days pre-treatment.
Twelve dogs were given a treatment of 0.5 mg/kg minimum dose of milbemycin
oxime one time and 12 were untreated. All dogs were necropsied 7 days post-treatment,
and all intestinal parasites were recovered, identified and counted.
Study Site:
CHK-R&D
17190 Polk Road
Stanwood, MI 49346
Study Director:
Dwight D. Bowman, Ph.D.
Animals:
21.5 to 27 week old Beagle dogs
13 males and 11 females
5.3 to 10.6 kg
Results:
One adult worm was recovered from the 12 treated dogs compared to 159 worms
from the 12 untreated control dogs. The milbemycin oxime treatment was calculated
to be 99.4% efficacious.
Conclusion:
This study demonstrated the efficacy of Interceptor Flavor Tabs against
T. leonina.
C. 1989 Clinical Field Trial
A clinical field trial (MT-147-00-89) was conducted during 1989-90 to evaluate
the safety and efficacy of monthly administration of milbemycin oxime for
the additional indications of removal and control of roundworms and whipworms
when used under typical veterinary conditions. Safety and efficacy data from
animals infected with roundworms was extracted to support the label change
for this supplement to the NADA. In this study, 100% (62 of 62) of the roundworm
cases were successfully treated by study completion (See Table 1).
(Eds note: The following table consists of 4 columns.)
TABLE 1 : Effects of Milbemycin Oxime on Removal and Control of Adult
Roundworm Infections in Dogs During Clinical Field Trials.
Investigator/ Treatment No. of Dogs Roundworm
Location Completing Study Infections
_________________________________________________________________________
Legg/ Milbemycin 15 5/5
Texas Filaribits Plus 14 3/3
Stocks/ Milbemycin 9 9/9
California Filaribits Plus 8 8/8
Utgard/ Milbemycin 62 48/48
Florida Filaribits Plus 63 56/55
Totals Milbemycin 86 62/62 = 100%
Filaribits 85 67/66 = 98%
_________________________________________________________________________
2 - "Cured" means no eggs found at final fecal examination.
D. Prevalence Study
National Prevalence of Canine Parasites based on Centrifugal Sucrose Flotation
Examinations of Fecal Specimens, B. L. Blagburn, D. S. Lindsay, J. L. Vaughan,
R. C. Lynn, W. J. Kelch, G. C. Ritchie, D. I. Hepler, July 6-10, 1995, Joint
Meeting of the American Association of Veterinary Parasitologists/American
Society of Parasitologists, Pittsburg, PA.
Fecal specimens (6,458 in total) were collected from dogs housed in animal
shelters and analyzed by Dr. Byron L. Blagburn, Auburn University. The animal
shelters were selected from the largest cities in each state. Fresh fecal
specimens, collected individually into 120 ml plastic specimen cups were examined
using the centrifugal sucrose flotation procedure. Specimen cups were placed
in styrofoam shipping boxes containing "cold pack" inserts, and
shipped to Dr. Blagburn's laboratory at Auburn University via overnight courier.
Specimens could contain more than one type of parasite. Thus, the percentages
presented below indicate the percent of specimens that contained the particular
parasite and do not add to 100 percent.
Parasite % of Total
__________________________________________
Toxocara canis 14.50
Toxascaris leonina 0.74
Ancylostoma caninum 19.20
Uncinaria stenocephala 1.00
Trichuris vulpis 14.30
Capillaria spp. 0.40
Giardia spp. 0.60
Isospora spp. 4.80
Sarcocystis spp. 0.80
Hammondia spp 0.06
Physaloptera spp. 0.05
Diplydium caninum 0.09
Taeniidae 0.60
__________________________________________
Conclusion: Based upon the 99.4% efficacy demonstrated in the dose confirmation
study, the 100% efficacy in the MT-147-00-89 Clinical Field Trial (including
the probability albeit low that some of the roundworms may have been Toxascaris
leonina cases), this data is adequate to support the expansion of the
roundworm claim.
The data in support of this supplemental NADA application complies with
the requirements of Section 512 of the Act and Section 514.111 of the implementing
regulations. It demonstrates that Interceptor® Flavor Tabs, when used
under the labeled conditions of use, are safe and effective.
According to the Center's supplemental approval policy (21 CFR 514.106),
this is a category II change. This supplement provides for an additional
claim for the removal and control of the adult roundworm, Toxascaris
leonina. This approval relied upon the safety and effectiveness data
in the parent application and evaluation of new efficacy data submitted
in the supplemental application.
Under section 512(c)(2)(F)(iii) of the Federal Food, Drug, and Cosmetic
Act (FFDCA), this approval qualifies for THREE years of marketing exclusivity
beginning on the date of approval because the supplemental application contains
reports of new clinical or field investigations (other than bioequivalence
studies) essential to the approval of the application and conducted or sponsored
by the applicant. The three years of marketing exclusivity applies only
to the additional roundworm claim (Toxascaris leonina) for which
the supplemental application was approved. This exclusivity period will
expire three years from the date of the approval letter.
The drug is restricted to use by or on the order of a licensed veterinarian
because professional expertise is required to determine the existence of
hookworm roundworm and/or whipworm infection. In addition, professional
expertise is required to determine the existence of heartworm infection,
and then properly treat existing heartworm infection prior to starting treatment
with Interceptor ® (milbemycin oxime) Flavor Tabs in a prevention program.
