Summary of
FDA Information:FREEDOM OF INFORMATION SUMMARY
GASTROGARD . (omeprazole)
I. GENERAL INFORMATION
NADA Number: 141-123
Sponsor: Merial Limited
2100 Ronson Road
Iselin, New Jersey 08830-3077
Generic Name: Omeprazole
Trade Name: GASTROGARD™
Marketing Status: Rx; For use by or
on the order of
a licensed veterinarian.
II. INDICATIONS FOR USE:
Gastrogard (omeprazole) is indicated for
the treatment and
prevention of
recurrence of
gastric ulcers in horses and
foals four weeks of
age and
older.
III. DOSAGE FORM, ROUTE OF ADMINISTRATION, RECOMMENDED
DOSAGE:
A. Dosage Form: GASTROGARD is an oral paste containing 2.28 g of
omeprazole per
syringe
B. Route of
Administration: For oral administration only.
C. Recommended Dosage: GASTROGARD should be administered once-a-day for
28
days at the
recommended dosage of
1.8 mg omeprazole/lb body weight (4 mg/kg).
The recommended dosage for
prevention of
recurrence of
ulcers after treatment is
0.9 mg omeprazole/lb body weight (2 mg/kg) for
30 days..GASTROGARD . Page 2 of
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NADA 141-123
IV. EFFECTIVENESS:
A. Dose Justification:
Omeprazole is a proton pump inhibitor that affects the secretion of
gastric acid into
the
stomach.
This inhibition of
acid secretion is the result of
specific binding of
omeprazole to
the H + /K + ATPase of
the parietal cells in the
gastric mucosa. Because this enzyme is
involved in the
final step in the
acid secretion cycle, omeprazole will inhibit acid secretion
in response to any stimulus.
The utility of
omeprazole in ulcer therapy is based upon the ability of
the drug to inhibit
acid secretion.
Therefore, a dosage of
omeprazole that is at or
near the dosage which
maximally inhibits acid secretion in horses should maximize ulcer therapy. Based on this
reasoning, dose selection for
omeprazole for
use in horses was
established based on its
effects in a pharmacodynamic model in which
acid secretion was
stimulated by
pentagastrin infusion.
Preliminary pharmacodynamic studies in cannulated horses showed that acid suppression was
incomplete when
omeprazole was
administered at a dosage of
3 mg/kg, and
maximal
acid suppression was
demonstrated at a dosage of
5 mg/kg. Similarly, preliminary efficacy
studies conducted in horses with gastric ulcers indicated that an improved response could
be expected at dosages higher than 3 mg/kg. On this basis, dosages of
4 mg/kg and
5 mg/kg were
used in a definitive dose selection study
described below. From
preliminary studies, ulcer healing rate was
determined to increase as horses remained on
omeprazole.
This was
confirmed in the
dose confirmation studies in which
ulcer healing and
ulcer improvement increased from
two weeks, through three weeks, to four weeks,
reaching a maximum of
92% at four weeks.
Pharmacodynamic study
(ASR 14646)
Purpose: To evaluate the effect of
omeprazole in suppressing gastric acid when
omeprazole is administered at 4 and
5 mg/kg/day to horses treated with pentagastrin
Investigators: J.E. Holste DVM, A. Merritt DVM and
F. M. Andrews DVM
Study Locations: Three sites were
used: Branchburg Farm, Somerville, NJ; Cherokee
Farm, Knoxville, TN; and
the University of
Florida, Gainesville, FL
Animals: 13 horses (8 females, 5 males) with a gastric cannula, and
ranging in age from
7
to 20 years.GASTROGARD . Page 3 of
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Study Design: A two-period crossover design was
used.
There was
a ten-day washout
period between periods. Pentagastrin-stimulated acid output was
measured at three time
points (6-8 hours, 14-16 hours, and
22-24 hours after administration) during each period.
Dosage Form: Paste, final market formulation
Route of
Administration: Oral
Dosage and
Frequency of
Treatment: Each dosage - 4 mg/kg and
5 mg/kg - was
administered to each horse daily for
15 days.
Controls: A gastric acid baseline was
established for
each horse prior to treatment.
Duration of
Study: 42 days.
Data Analysis: Percent inhibition of
acid output was
analyzed by a mixed model analysis of
variance to compare the effects of
treatment at 4 mg/kg vs 5 mg/kg.
Results:
Table 1: Percent inhibition of
pentagastrin-stimulated acid secretion (least squares
mean ± standard deviation)
Dosage 8 h 16 h 24 h
4 mg/kg/d 98.9 ± 1.5 95.0 ± 7.7 90.3 ± 6.5
5 mg/kg/d 99.5 ± 0.7 97.7 ± 2.5 92.3 ± 5.5
Conclusions: Omeprazole at 4 mg/kg/day was
selected as a dose that would effectively
inhibit gastric acid secretion for
24 hours.
Observations: No adverse reaction was
reported..GASTROGARD . Page 4 of
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NADA 141-123
B. Dose Confirmation
Four well-controlled, blinded, dose confirmation trials were
conducted under
a single
protocol.
Purposes: To confirm the effectiveness of
omeprazole at 4 mg/kg/day for
treatment of
gastric ulcers in horses, and
to determine the dosage of
omeprazole required to prevent
recurrence of
gastric ulcers after the treatment regimen was
completed.
Study Designations, Investigators and
Study Locations:
Study Investigator Location
ASR 15212 F. M. Andrews, DVM Poindexter Farms, Denison, TX 72020
ASR 15215 F. Hughes, DVM Sharon Biamonte Training Center,
Morriston, FL 32668
ASR 15235 R. L. Sifferman, DVM Poindexter Farms, Denison, TX 72020
ASR 15238 W. Bernard, DVM The Kentucky Horse Center, Lexington,
KY 40511
Animals: 100 clinically healthy, adult, Thoroughbred racehorses in training ranging in
age from
2 to 11 years. Horses were
diagnosed with gastric ulcers using gastric
endoscopy.
Dosage Form: Paste
Route of
Administration: Oral
Dosage and
Frequency of
Treatment: For the first 28 days of
the studies, omeprazole was
administered daily at 4 mg/kg. For the next 30 days, daily omeprazole dosages of
2 and
4
mg/kg were
tested.
Controls: Control horses were
sham dosed.
Duration of
Study: 58 days
Study Design: Twenty-five horses were
assigned to the control group and
seventy-five
horses to the treatment group, which
consisted of
daily administration of
omeprazole at 4.GASTROGARD . Page 5 of
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NADA 141-123
mg/kg. In the first part of
the study
, severity of
ulcers was
confirmed at baseline and
reassessed after 14, 21, and
28 days. Ulcer severity was
assessed using gastric endoscopic
examinations and
a uniform scoring system as follows:
Ulcer scoring system: A score for
the worst stomach lesion was
recorded for
each horse.
0= intact mucosal epithelium (can have reddening/hyperkeratosis)
1=small single or
small multifocal lesions
2=large single or
large multifocal lesions
3=extensive lesions with areas of
deep ulceration
The presence of
reddening or
hyperkeratosis was
also recorded.
In the second part of
the study
, 75 horses that had received omeprazole at 4 mg/kg for
28
days were
reassigned either to continue on a daily dosage of
4 mg/kg for
an additional 30
days, or
to a reduced daily dosage of
2 mg/kg, or
to sham dosing with an empty syringe
(25 horses/group).
The original 25 horses assigned to sham dosing in part one of
the study
were continued on sham treatment. Ulcers were
reassessed in all groups at the
end of
the 30 days.
Data Analysis: The pooled data on change in ulcer score for
animals in all four trials were
analyzed non-parametrically using a Cochran-Mantel-Haenszel procedure to assess
differences between omeprazole and
control in the
first 28 days, and
to assess differences
between dosages in the
next 30 days, and
to compare ulcer status of
horses maintained on
omeprazole vs. those discontinued from
treatment.
Results: Horses treated with omeprazole for
28 days had significantly (p<0.01) greater
improvement in ulcer score than the controls. Ulcer scores were
improved (lower gastric
score at day 28 vs. pretreatment score) in 92% of
omeprazole treated horses after 28 days of
treatment compared to only 32% of
control horses. Of the omeprazole treated horses,
77% had complete ulcer healing (lesion score of
0) vs. 4% of
the control horses had
completely healed.
For the second part of
the study
, prevention of
recurrence was
represented by the % of
horses with gastric lesion scores at day 57 that were
healed, improved from
the day 27
score, or
did not change from
the day 27 score for
each treatment group.
There was
a
significant difference (p<0.01) in prevention of
recurrence between the horses removed from
omeprazole treatment vs. those continuing on omeprazole at either the 2 or
4 mg/kg
dose of
omeprazole. However; there was
no significant difference between the effects of
omeprazole at dosages of
2 and
4 mg/kg in prevention of
recurrence of
ulcers.
Of those horses treated with placebo for
the second part of
the study
, 8% of
the controls were
healed (See Table 2) at the
end of
57 days. None of
the horses in this group.GASTROGARD . Page 6 of
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NADA 141-123
improved from
their day 27 scores, 8% maintained the same score, and
84% worsened
compared to their day 27 scores.
Of those horses treated at 2 mg/kg for
the second part of
the study
, 76% of
the horses had
healed gastric ulcers, no horses improved from
their day 27 scores, 8% maintained the
same score and
16% worsened as compared to their day 27 scores.
Of those horses treated at 4 mg/kg for
the second part of
the study
, 84% were
healed, 4%
improved over their day 27 scores, none of
the horses maintained the same score and
12%
worsened as compared to their day 27 scores.
Table 2. Day 57 results of
study
for horses in each treatment group (0 = placebo, 2 mg
omeprazole/kg, 4 mg omeprazole/kg) represented as percent healed, improved, no change and
worsened as compared to the day 27 gastric lesion score.
Day 57 0 2
mg/kg
4
mg/kg
% healed* 8 76 72
% improved from
day 27
score*
0 0 4
% no change from
day
27 score*
8 8 0
% worsend from
day 27
score
84 16 12
*prevention of
recurrence is represented by the percent of
horses healed, improved or
no change from
the
day 27 gastric lesion score, i.e., for
the 2 mg/kg treatment group 76 + 0 + 8 = 84%
Conclusions: The omeprazole paste formulation, administered daily at 4 mg/kg for
28
days, is effective for
treatment of
gastric ulcers in horses. Continuation of
treatment for
30
days at a dosage of
2 mg/kg/day effectively prevents recurrence of
gastric ulcers while
being treated.
Observations: No adverse reactions were
reported.
C. Clinical Field Trial.GASTROGARD . Page 7 of
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A multi-center well-controlled, blinded, clinical field trial was
conducted under
a single
protocol. Six sites included clinically healthy horses and
foals with gastric ulcers.
Ulcers were
diagnosed by gastric endoscopic examination.
Clinical Field Trial in Horses with Gastric Ulcers
Purpose: To confirm the safety, efficacy and
acceptability of
omeprazole at 4 mg/kg/day under
field conditions.
Investigators and
Trial Locations:
Study Investigator Location
ASR 15244 S. McClure, DVM, PhD Wea Valley Ranch, Lafayette, IN 47905
ASR 15245 G. W. White, DVM Blue Ribbon Downs, Sallisaw, OK 74955
ASR 15247 C. G. MacAllister, DVM Equine Research Park, Stillwater, OK
74075
ASR 15250 R. L. Sifferman, DVM Los Alamitos Race Track, Los Alamitos,
CA 90720
ASR 15264 R. L. Sifferman, DVM Richard Wise Farm, Monett, MO 65708
Shawn Corcoran Farm, Edwardsville, IL
62025
A. B. Twisdale Farm, Mason, TN 38049
Paul Nelms Farm, Lewisburg, TN 37091
ASR 15266 N. J. Vatistas, BVSc, PhD Peninsula Equine, Inc., Menlo Park, CA
94026
Animals: 139 clinically healthy horses ranging in age from
4 weeks to 28 years.
A total of
26 foals between 4 and
7 weeks old were
included. Breeds included: Standardbreds,
Thoroughbreds, Quarterhorses, Appaloosas, Paints, Tennessee Walking Horses, Arabians,
Holsteiner, Hanoverian, Swedish, Danish and
Dutch Warmbloods, ponies, Trakehner
cross, Warmblood crosses and
Quarterhorse crosses.
Dosage Form: Paste
Route of
Administration: Oral.GASTROGARD . Page 8 of
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NADA 141-123
Dosage and
Frequency of
Treatment: Omeprazole was
administered daily at 4 mg/kg for
28 days.
Controls: Control horses were
sham dosed daily.
Duration of
Study: 28 days
Study Design: Using gastric endoscopic examinations and
the standardized scoring
system used in the
dose confirmation trials, severity of
ulcers was
confirmed at baseline and
reassessed after 28 days of
daily treatment with omeprazole at 4 mg/kg. Each horse was
examined clinically by a veterinarian before treatment began and
again after
approximately 14 and
28 days on trial. Ulcer severity was
assessed using gastric
endoscopic examinations and
a uniform scoring system as follows:
Ulcer scoring system: A score for
the worst stomach lesion was
recorded for
each horse.
0= intact mucosal epithelium (can have reddening/hyperkeratosis)
1=small single or
small multifocal lesions
2=large single or
large multifocal lesions
3=extensive lesions with areas of
deep ulceration
The presence of
reddening or
hyperkeratosis was
also recorded.
Data Analysis: The pooled data on change in ulcer score from
the six sites were
analyzed
non-parametrically using a Cochran-Mantel-Haenszel procedure to assess differences
between omeprazole and
control after 28 days. Incidences of
observations on health
condition were
analyzed by a Mantel-Haenszel test.
Results: Horses treated with omeprazole had significantly (p<0.01) greater improvement
in ulcer score than the controls. Improvement is defined as a lower gastric lesion score at
day 28 compared to pretreatment score. Ulcers scores were
improved in 99.0% of
omeprazole treated horses compared to 32.4% of
control horses. Ulcers were
healed
(gastric score of
0) in 86.7% of
omeprazole treated horses compared to 8.8% of
control
horses.
There was
no clinically significant difference between groups in incidences of
observations on health condition.
The paste was
well accepted by horses and
foals.
Concomitant medications including anesthetics, anthelmintics, antibiotics, diuretics,
steroidal and
non-steroidal anti-inflammatory agents, tranquilizers and
vaccines were
administered during the field trials without adverse effects.
Observations: No adverse reactions were
reported..GASTROGARD . Page 9 of
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Conclusions: The omeprazole paste formulation, administered daily at 4 mg/kg for
28
days, is safe, acceptable, and
effective for
treatment of
gastric ulcers in horses and
foals
four weeks of
age and
older.
Acceptability Field Trials in Horses Without Gastric Ulcers
These trials followed the same protocol (dosage form, route of
administration, dosage and
frequency of
treatment, use of
controls, and
duration of
study
) as the six sites above, but
there was
no requirement for
pre-existing ulcers.
Purpose: To evaluate acceptability of
the paste to foals and
yearlings.
Investigator and
Trial Locations:
Study Investigator Location
ASR 15241 M. J. Murray, DVM Virginia Tech Mare Center, Middleburg,
VA 20117
ASR 15242 M. J. Murray, DVM Virginia Tech Mare Center, Middleburg,
VA 20117
Animals: 40 Thoroughbred foals/yearlings, ranging in age from
11 to 16 weeks and
from
15 to 17 months.
There were
18 female foals and
22 males.
Results: These studies demonstrated that administration of
4 mg omeprazole/kg to
weanlings and
yearlings was
clinically safe and
that product acceptability was
satisfactory.
This study
was not designed to evaluate efficacy; however, endoscopic
exams were
performed pre and
post treatment. As a result, it was
found that two of
the foals in study
ASR 15241, which
initially did not have ulcers, developed ulcers while on
omeprazole (4 mg/kg). Likewise, one of
the treated yearlings which
was
free of
ulcers at the
start of
the trial, also developed ulcers by the end of
the study
. It appears from
these
observations, that the
4 mg/kg of
omeprazole did not prevent the development of
ulcers in
these animals.
Conclusion: Omeprazole paste for
horses was
clinically safe and
acceptable when
administered to foals and
yearlings under
field conditions; however, it did not prevent the
development of
ulcers in several foals.
Observations: No adverse reactions were
reported..GASTROGARD . Page 10 of
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NADA 141-123
V. TARGET ANIMAL SAFETY
Four controlled, GLP safety trials were
conducted using exaggerated dosages of
the marketed formulation of
omeprazole paste for
horses. One study
was conducted in foals.
Two studies were
conducted in adult horses of
both sexes. One study
evaluated
reproductive safety in breeding stallions.
A . Safety Trial in Foals (ASR 15237)
Purpose: To evaluate the health effects of
omeprazole when
administered orally to young
horses at 4, 12 and
20 mg/kg (1, 3 and
5X the use level) daily for
three months.
Investigator and
Trial Location: Raymond Plue DVM
Merial Missouri Research Center
Fulton, MO 65251
Animals: 24 Tennessee Walking Horse foals (12 males, 12 females), ranging in age from
66 to 110 days.
Dosage Form: Paste
Route of
Administration: Oral
Dosage and
Frequency of
Treatment: Foals were
dosed daily for
91 days with
omeprazole at either 4, 12 or
20 mg/kg (1, 3, or
5X). Each treatment group consisted of
6
foals (3 males, 3 females).
Controls: 6 control foals (3 males, 3 females) were
sham dosed daily using empty
syringes.
Duration of
Study: 91 days
Evaluation: Foals were
observed twice daily for
clinical signs of
toxicity and
health
problems. Blood chemistry, hematology and
physical examinations were
conducted on Days
-7, 15, 29, 59 and
90 for
all foals. Hematology profile included RBC, WBC, platelet count,
hemoglobin, PCV, MCV, MCH, MCHC, WBC differential, and
RBC morphology.
Chemistry profile included calcium, phosphorus, sodium, potassium, chloride, AST, GGT,
cholesterol, triglycerides, glucose, total bilirubin, total protein, total globulin, A/G ratio,
blood urea nitrogen, creatinine, alkaline phosphatase, sorbitol dehydrogenase, serum iron, and
albumin. Physical exams evaluated general appearance, appearance of
feces,.GASTROGARD . Page 11 of
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NADA 141-123
respiration rate, temperature, heart rate, auscultation of
the GI tract, and
appearance of
oral and
ocular mucous membranes.
Foals were
necropsied on Day 91, 92 or
93. Following a gross macroscopic observation,
samples were
collected and
submitted for
histopathology from
the adrenals, lungs, heart,
liver, mesenteric lymph node, lower esophagus, stomach (squamous, fundic, and
pyloric),
duodenum, jejunum, ileum, cecum, spleen, submandibular lymph node, large colon,
rectum, gonads, prostate, uterus, pancreas, kidneys, urinary bladder, thymus, and
small
colon. Any gross lesion noted was
also submitted.
A bone marrow smear from
each foal was
also prepared at necropsy.
Results: GGT levels were
significantly elevated in the
20 mg/kg dosage group ( p=
0.0689). Necropsy results showed no evidence of
hepatic disease.
Mean stomach to body weight ratio was
higher for
foals in the
3X and
5X groups than for
controls. No abnormalities of
the stomach were
evident on histological examination, and
this was
considered to be of
no clinical relevance.
Statistically significant differences among treatment groups were
found for
albumin,
albumin/globulin (females), globulin, cholesterol, SDH, sodium, total protein, calcium,
chloride, hematocrit, hemoglobin, lymphocytes, and
monocytes (females). However,
these changes were
not clinically significant.
No statistically significant treatment effects were
found for
alkaline phosphatase, AST,
BUN, creatinine, glucose, serum iron, phosphorus, potassium, total bilirubin,
triglycerides, albumin/globulin (males), MCH, MCV, RBC, RDW, WBC, neutrophils, or
eosinophils.
Conclusion: No treatment related adverse effects were
seen following administration of
omeprazole to young horses orally at a dose of
4 mg/kg (1X) once daily for
91 days.
Omeprazole administered to young horses at doses of
20 mg/kg for
91 days resulted in
elevations of
GGT levels. Doses of
12 mg/kg and
20 mg/kg may result in increased stomach
weights. Neither of
these findings were
considered clinically significant, since
histopathology of
the liver and
stomach was
considered normal.
B. Safety Trial in Adult Horses (ASR 15205)
Purpose: To determine the occurrence of
any adverse health effects of
omeprazole when
administered orally at 20 mg/kg (5X the use level) daily for
3 months.
Investigator and
Trial Location: Raymond Plue DVM
Merial Missouri Research Center.GASTROGARD . Page 12 of
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Fulton, MO 65251
Animals: 18 adult Thoroughbred horses (9 males, 9 females), ranging in age from
4 to 20
years.
Dosage Form: Paste
Route of
Administration: Oral
Dosage and
Frequency of
Treatment: Twelve horses were
dosed daily for
3 months with
omeprazole at 20 mg/kg (5X). One group of
6 horses (3 male, 3 female) was
necropsied
after 3 months.
The other group (3 male, 3 female) was
discontinued from
treatment at the
end of
3 months and
kept under
observation for
an additional 82 days to determine the
reversibility of
any adverse reactions that may have been apparent after necropsy of
the first treatment group.
Controls: 6 control horses (3 male, 3 female) were
sham dosed daily using empty
syringes.
These horses were
necropsied after 3 months.
Duration of
Study: 3-6 months
Evaluation: Horses were
observed twice daily for
clinical signs of
toxicity and
health
problems. Blood chemistry, hematology and
physical examinations were
conducted before
treatment and
on Days 14, 29, 61 and
90. Necropsies were
conducted on Day 91 or
92.
Results: There were
no clinical, hematological, blood chemistry, gross or
microscopic
pathological abnormalities related to treatment in any of
the groups. Gastric ulcers were
present in each of
the 6 control horses and
in none of
the 6 omeprazole-treated horses that were
necropsied (p<0.01). Because no treatment-related adverse effects were
observed in the
horses necropsied at 3 months, the
remaining six horses were
not necropsied.
Conclusion: There were
no treatment related adverse effects observed in adult horses after
treatment with omeprazole orally at a dose of
20 mg/kg (5X) daily for
3 months.
C. 10X Tolerance Trial in Adult Horses (ASR 15251)
Purpose: To evaluate the safety of
omeprazole when
administered orally at 40 mg/kg
(10X the use level) daily for
21 days.
Investigator and
Trial Location: Raymond Plue DVM
Merial Missouri Research Center
Fulton, MO 65251.GASTROGARD . Page 13 of
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Animals: 6 adult Thoroughbred horses (3 males, 3 females), ranging in age from
3 to 17
years
Dosage Form: Paste
Route of
Administration: Oral
Dosage and
Frequency of
Treatment: Horses were
dosed daily for
21 days with
omeprazole at 40 mg/kg (10X). Two males and
two females received this dosage.
Controls: 2 control horses (1 male, 1 female) were
sham dosed daily using empty
syringes.
Duration of
Study: 3 weeks
Evaluation: Horses were
observed for
general health at least twice daily. Physical
examinations were
conducted on Day -1 and
on Days 2, 9 and
21. Blood samples were
drawn for
serum chemistry and
hematology evaluation at these times. Physical
examination included observations of
general appearance, appearance of
feces, respiration
rate, temperature, heart rate, auscultation of
the gastrointestinal tract, and
appearance of
oral and
ocular mucous membranes.
Hematology profile included RBC, WBC, platelet count, hemoglobin, PCV, MCV, MCH,
MCHC, WBC differential, and
RBC morphology. Chemistry profile included calcium,
phosphorus, sodium, potassium, chloride, AST, GGT, cholesterol, triglycerides, glucose,
total bilirubin, total protein, total globulin, A/G ratio, urea nitrogen, creatinine, alkaline
phosphatase, sorbitol dehydrogenase, and
serum iron. Hematology and
chemistry data were
not subjected to statistical analysis due to the small sample size.
Horses were
necropsied on Day 22.
The description of
gross lesions, stomach weights, and
liver weights were
recorded; and
gross lesions and
tissues were
histologically
examined.
Results: No adverse effects, gross or
histologic lesions attributable to omeprazole were
noted
during the study
. On necropsy, stomach ulcers were
identified in one control horse and
none of
the omeprazole-treated horses.
Conclusion: Omeprazole administered to adult horses at 40 mg/kg (10X) daily for
21 days
had no adverse effects on clinical chemistry, hematology, physical examination, and
macroscopic or
microscopic assessments at necropsy..GASTROGARD . Page 14 of
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D. Safety Trial in Breeding Stallions (ASR 15009)
Investigator and
Trial Location: A. Alexander, BVSc (Study Director)
N. Perkins, BVSc, MS, DipACT (Theriogenologist)
Sovereign Lodge Stud Limited
Ohau, New Zealand
Purpose: To determine the effect of
omeprazole on reproductive parameters of
breeding
stallions when
administered orally at 12 mg/kg (3X the use level) daily for
10 weeks.
Animals: 20 stallions (Thoroughbred or
Standardbred) ranging in age from
3 to 12 years.
Stallions were
selected based on designated baseline minimum standards for
semen
parameters (total number of
sperm, progressive motility of
sperm, sperm morphology, and
seminal pH) prior to entering the study
. In addition, all stallions were
examined and
determined to have normal genitalia prior to inclusion in the
study
.
Dosage Form: Paste
Route of
Administration: Oral
Dosage and
Frequency of
Treatment: 10 stallions were
dosed daily for
71 days with
omeprazole at 12 mg/kg (3X).
Controls: 10 control stallions were
sham dosed daily for
71 days using an empty syringe.
Duration of
Study: 10 weeks
Evaluation: Ten pairs of
stallions were
formed based on a ranking of
descending average
daily sperm output on Days -11 to -2. In each pair, one stallion was
randomly assigned to
receive omeprazole and
the other to control. Semen was
collected from
each stallion on
Days -16 to -12 and
Days 56 to 60 to stabilize extragonadal reserves. Semen was
collected for
analysis on Days -11 to -2 and
Days 61 to 70. Reproductive behavior was
evaluated on
all days that semen was
collected for
analysis. Semen was
evaluated for
the following:
volume collected (gel and
gel-free), gross appearance, seminal pH, percent progressively
motile sperm, sperm concentration, and
total number of
sperm in the
gel-free fraction.
Sperm morphology (normal, abnormal head, detached head, proximal droplet, distal droplet,
abnormal midpiece, abnormal tail) was
determined.
The presence of
mononuclear cells or
other cell types was
also noted.
External and
internal palpation of
the genitals was
conducted on Days -21, -19, -18, -17 or
-16, and
on Day 71.
The exam included testis size (length, width, height) and
consistency,.GASTROGARD . Page 15 of
16
NADA 141-123 and
determination of
any gross abnormalities of
the epididymis and
spermatic cord.
The
prepuce, penis, and
scrotum were
examined. Internally, the
inguinal rings, vesicular gland,
ampullae, and
prostatic lobes were
evaluated.
Results: No treatment-related adverse effects were
seen on the variables evaluated.
Conclusion: Omeprazole administered to stallions daily for
71 days at 12 mg/kg/day (3X the
recommended dose) had no adverse effects on semen quality or
breeding behavior.
VI. HUMAN SAFETY
Data on human safety, pertaining to consumption of
drug residues in food, were
not
required for
approval of this NADA.
The drug is labeled for
use in horses, which
are non-food
animals.
The following Warning statement appears on the product label: "Not for
use in horses intended for
human consumption."
VII. AGENCY CONCLUSIONS:
The data in support of
this NADA comply with the requirements of
Section 512 of
the Federal Food, Drug, and
Cosmetic Act and
Section 514.111 of
the implementing
regulations.
The data demonstrate that Gastrogard ™ (omeprazole), when
used under
labeled conditions, is safe and
effective.
The drug is restricted to use by or
on the order of
a licensed veterinarian because
professional expertise is judged to be critical in the
diagnosis of
gastric ulcer disease in
horses.
Under Section 512(c)(2)(F)(i) of
the Federal Food, Drug, and
Cosmetic Act, this approval
qualifies for
FIVE years of
marketing exclusivity beginning on the date of
approval
because no active ingredient (including any ester or
salt of
the active ingredient) has been
approved in any other application.
Patent Information: US Patent 4255432, Expiration April 5, 2001; US Patent 5708017,
Expiration April 4, 2015.
VIII. PRODUCT LABELING
Syringe Carton
Package Insert.GASTROGARD . Page 16 of
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NADA 141-123
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