Data demonstrating the effectiveness
of IVOMEC Pour-On for Cattle for previously approved indications are discussed
in the parent NADA 140-841 FOI summary (approval date December 4, 1990). Data
from the following dose confirmation trials demonstrate that IVOMEC Pour-On
for Cattle given at the recommended dosage controls infections of Ostertagia
ostertagi, Haemonchus placei, Trichostrongylus axei, Oesophagostomum
radiatum, Cooperia punctata, and Cooperia oncophora for 14
days after treatment.
A. Dose Confirmation
Trial ASR 14346
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms.
2. Investigator:
Larry R. Cruthers, M.S.,
Ph.D.
PLRS Laboratories, Inc.
Corapeake, North Carolina
3. General design:
a. Purpose: To determine the period
after treatment during which infections of gastrointestinal roundworms are controlled.
b. Animals: Twenty (20) beef crossbred
calves (10 per group). Animals were approximately 6 to 8 months old and weighed
182 to 266 kg at the start of the study. Animals were free of patent infections
at the time of treatment.
c. Controls: Negative controls
received the vehicle for IVOMEC Pour-On.
d. Infection: Infective larvae
were given to each animal daily, starting on the day after treatment, according
to the following schedule: Ostertagia ostertagi (1000 per day for 14
days); Haemonchus placei (500 per day for 14 days); Trichostrongylus
axei (1000 per day for 14 days); and Cooperia oncophora (500 per
day for 14 days).
e. Dosage form: The dosage form
was a solution containing 5 mg ivermectin per ml.
f. Route of administration: Topical
g. Dose: 1 ml/10 kg body weight
(500 mcg ivermectin/kg body weight) once.
h. Test duration: 41 or 42 days
after treatment
i. Pertinent variables measured:
Worm counts were determined at necropsy.
4. Results: The following parasites
had a minimum of six adequately infected control animals and > or equal to
90% efficacy was demonstrated against them, the level required to justify a
claim.
|
Arithmetic mean |
| Parasite |
Control |
IVOMEC Pour-On |
Percent reduction |
| Ostertagia ostertagi |
492.0 |
0.0 |
100 |
| Haemonchus placei |
340.0 |
2.0 |
99.4 |
| Trichostrongylus axei |
704.0 |
4.0 |
99.4 |
| Cooperia oncophora |
680.0 |
6.0 |
99.1 |
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of nematodes
in non-medicated cattle) - (Arithmetic mean number of nematodes in ivermectin-treated
cattle)] ÷ (Arithmetic mean number of nematodes in non-medicated cattle)
x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this study,
IVOMEC Pour-On for Cattle controlled infections of Ostertagia ostertagi,
Haemonchus placei, Trichostrongylus axei, and Cooperia oncophora
for 14 days after treatment.
7. Adverse reactions:
There were no adverse reactions
during the study.
Trial ASR 14553
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms.
2. Investigator:
Bruce N. Kunkle, D.V.M.,
M.S., Ph.D.
Merck & Co., Inc.
Fulton, Missouri
3. General design:
a. Purpose: To determine the period
after treatment during which infections of gastrointestinal roundworms are controlled.
b. Animals: Twenty-eight (28) crossbred
calves (7 per group). Animals were approximately 6 months old and weighed 152
to 221 kg at the start of the study. All animals were treated with another anthelmintic
during the acclimation period to eliminate any existing infections.
c. Controls: Negative controls
received no treatment. Two groups received medications which are not pertinent
to this document.
d. Infection: Infective larvae
were given to each animal daily, starting on the day of treatment, according
to the following schedule: Trichostrongylus axei (1000 per day for 15
days); Cooperia punctata (500 per day for 15 days); Cooperia oncophora
(500 per day for 15 days); and Oesophagostomum radiatum (100 per day
for 22 days).
e. Dosage form: The dosage form
was a solution containing 5 mg ivermectin per ml.
f. Route of administration: Topical
g. Dose: 1 ml/10 kg body weight
(500 mcg ivermectin/kg body weight) once.
h. Test duration: 49 to 51 days
after treatment
i. Pertinent variables measured:
Worm counts were determined at necropsy.
4. Results: The following parasites
had a minimum of six adequately infected control animals and > or equal to
90% efficacy was demonstrated against them, the level required to justify a
claim.
|
Arithmetic mean |
| Parasite |
Control |
IVOMEC Pour-On |
Percent reduction |
| Trichostrongylus axei |
5491.4 |
2.9 |
>99.9 |
| Oesophagostomum radiatum |
121.4 |
0 |
100.0 |
| Cooperia punctata |
3082.8 |
2.9 |
>99.9 |
| Cooperia oncophora |
300.0 |
2.9 |
99.0 |
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of nematodes
in non-medicated cattle) - (Arithmetic mean number of nematodes in ivermectin-treated
cattle)] ÷ (Arithmetic mean number of nematodes in non-medicated cattle)
x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this study,
IVOMEC Pour-On for Cattle controlled infections of Trichostrongylus axei,
Cooperia punctata and Cooperia oncophora for 14 days after treatment
and Oesophagostomum radiatum for 22 days after treatment.
7. Adverse reactions:
Some animals had loose stools during
the trial and one animal vomited. These health problems were not believed to
be related to the experimental treatments.
Trial ASR 15185
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms.
2. Investigator:
Charles H. Courtney, D.V.M.,
Ph.D.
University of Florida
Gainesville, Florida
3. General design:
a. Purpose: To determine the period
after treatment during which infections of gastrointestinal roundworms are controlled.
b. Animals: Twenty (20) Angus cross
calves (10 per group). Animals were approximately 8 to 10 months old and weighed
208 to 260 kg at the start of the study. Animals were free of patent infections
at the time of treatment.
c. Controls: Negative controls
received the vehicle for IVOMEC Pour-On.
d. Infection: Infective larvae
were given to each animal daily, starting on the day after treatment, according
to the following schedule: Ostertagia ostertagi (1000 per day for 14
days); Haemonchus spp. (500 per day for 14 days); Trichostrongylus
axei (1000 per day for 14 days); and Cooperia spp. (500 per day for
14 days).
e. Dosage form: The dosage form
was a solution containing 5 mg ivermectin per ml.
f. Route of administration: Topical
g. Dose: 1 ml/10 kg body weight
(500 mcg ivermectin/kg body weight) once.
h. Test duration: 42 or 43 days
after treatment
i. Pertinent variables measured:
Worm counts were determined at necropsy.
4. Results: The following parasites
had a minimum of six adequately infected control animals and > or equal to
90% efficacy was demonstrated against them, the level required to justify a
claim.
|
Arithmetic mean |
| Parasite |
Control |
IVOMEC Pour-On |
Percent reduction |
| Ostertagia ostertagi |
496.0 |
0.2 |
>99.9 |
| Haemonchus placei |
227.6 |
0.0 |
100 |
| Trichostrongylus axei |
1268.1 |
0.0 |
100 |
| Cooperia punctata |
389.1 |
0.0 |
100 |
| Cooperia oncophora |
223.4 |
0.0 |
100 |
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of nematodes
in non-medicated cattle) - (Arithmetic mean number of nematodes in ivermectin-treated
cattle)] ÷ (Arithmetic mean number of nematodes in non-medicated cattle)
x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this study,
IVOMEC Pour-On for Cattle controlled infections of Ostertagia ostertagi,
Haemonchus placei, Trichostrongylus axei, Cooperia punctata,
and Cooperia oncophora for 14 days after treatment.
7. Adverse reactions:
One animal hit its nose against
a fence resulting in a bloody nose. This event was not believed to be related
to the experimental treatments.
Trial ASR 13980
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms and lungworms.
2. Investigator:
R.E. Plue, D.V.M.
Springdale, Arkansas
3. General design:
a. Purpose: To determine the period
after treatment during which infections of gastrointestinal roundworms are controlled.
b. Animals: Thirty-five (35) Holstein
calves (7 per group). Animals were approximately 6 to 8 months old and weighed
142.9 to 207.3 kg at the start of the study. Animals were free of patent infections
at the time of treatment.
c. Controls: Negative controls
were untreated. Three groups received a medication or were treated at a time
not pertinent to this document.
d. Infection: Infective larvae
were given to each calf 14 days after treatment, according to the following
schedule: Oesophagostomum radiatum (1,000).
e. Dosage form: The dosage form
was a solution containing 5 mg ivermectin per ml.
f. Route of administration: Topical
g. Dose: 1 ml/10 kg body weight
(500 mcg ivermectin/kg body weight) once.
h. Test duration: 49 to 51 days
after treatment
i. Pertinent variables measured:
Worm counts were determined at necropsy which was 49, 50, or 51 days after treatment
and 35, 36, or 37 days after the last larvae were administered.
4. Results - The following parasite
had a minimum of six adequately infected control animals and at 14 days from
treatment to infection demonstrated > or equal to 90% efficacy, the level
required to justify a claim:
|
Arithmetic mean |
| Parasite |
Control |
IVOMEC Pour-On |
Percent reduction |
| Oesophagostomum radiatum |
76 |
2.8 |
96 |
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of nematodes
in non-medicated cattle) - (Arithmetic mean number of nematodes in ivermectin-treated
cattle)] ÷ (Arithmetic mean number of nematodes in non-medicated cattle)
x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this study,
IVOMEC Injection for Cattle controlled infections of Oesophagostomum radiatum
for 14 days after treatment.
7. Adverse reactions:
There were no adverse reactions
reported.
The data submitted in support of
this supplemental NADA comply with the requirements of section 512 of the Act
and demonstrate that ivermectin topical formulation, when used under the proposed
conditions of use, is safe and effective for the control of infections of Ostertagia
ostertagi, Oesophagostomum radiatum, Haemonchus placei, Trichostrongylus
axei, Cooperia punctata, and Cooperia oncophora for 14 days
after treatment.
For cattle the tolerance of residues
are specified in 21 CFR 556.344. A tolerance for the marker residue (22, 23-dihydro-avermectin
B1a) of ivermectin is 100 ppb in the liver (target tissue). The withdrawal time
is 48 days following one topical application of IVOMEC Pour-On® for Cattle
as specified in 21 CFR 524.1193.
The original approval of ivermectin
topical formulation was as an over-the-counter drug. Adequate directions for
use have been written for the layman, and the conditions for use prescribed
on the labeling are likely to be followed in practice. Therefore, the Center
for Veterinary Medicine (CVM) has concluded that this product shall retain over-the-counter
marketing status.
Under the Center's supplemental
approval policy 21 CFR 514.106(b)(2), this is a Category II change. The approval
of this change did not require a reevaluation of the safety or effectiveness
data in the parent application.
Under section 512(c)(2)(F)(iii)
of the FFDCA, this approval for food producing animals qualifies for THREE years
of marketing exclusivity beginning on the date of approval because the supplemental
application contains substantial evidence of the effectiveness of the drug involved,
any studies of animal safety, or, in the case of food producing animals, human
food safety studies (other than bioequivalence or residue studies) required
for the approval of the application and conducted or sponsored by the applicant.
The three years of marketing exclusivity applies only to the new claim for the
control of Ostertagia ostertagi, Oesophagostomum radiatum, Haemonchus
placei, Trichostrongylus axei, Cooperia punctata, and Cooperia
oncophora for 14 days after treatment in cattle for which the supplemental
application was approved.
