factbook

1
ClinacoxEfficacy profile
Ing. Leo SulsInternational Marketing
Manager Janssen Animal Health
2
Battery trials Clinacox
3
A.C.I. - Battery trials
PPM
Eimeria 0 0.1 0.5 1 5 10
tenella 106 199 199 200 198 201
acervulina 134 157 190 200 201 199
necatrix 90 186 196 197 197 198
brunetti 114 170 193 193 196 197
maxima 129 177 184 193 194 196
mitis 124 159 174 180 196 195
CLINACOX 0.5 PREMIX(2-5 replicates x 8 birds)
4
Effect of 1 ppm diclazuril on lesion scores and
oocyst excretion(OPG) of birds infected with a
single Eimeria species(6 days p.i.) (Vanparijs,
1989)
average lesion scores OPG (X
1000) IUC diclazuril IUC diclazuril E.
tenella 3.5 0 469 0 E. acervulina 2.2 0 40
7 0 E. necatrix 3.4 0.4 74 0 E.
brunetti 2.9 0.2 143 0 E. maxima 2.4 1.3 2
7 0 E. mitis 2.2 0.4 248 17
5
Stage of action - results
6
When can lesions occur?

• COCCIDIOCIDAL EFFECT ONLY AGAINST LATE STAGES
  (E.maxima E.brunetti)
• HIGH INFECTION PRESSURE !
• MAXIMA
• BRUNETTI NECATRIX
• CLEAN-UP TAKES TIME
• UNDERSTANDING STAGE OF ACTION IS CRUCIAL

7
Stage of action - strain differences

• JAPANESE NAÏVE STRAINS
• NO OOCYST EXCRETION
• CLINICAL SIGNS
• ACERVULINA LESIONS (SLIGHT)

8
Clinacox and E. maxima

• Example The US label claim
• For the prevention of coccidiosis caused by
  E. tenella, E. necatrix, E. brunetti, E.
  acervulina, E. mitis and E. maxima.
• Because diclazuril is effective against E. maxima
  later in its lifecycle, subclinical intestinal
  lesions may be present for a short time after
  infection. Diclazuril was shows in studies to
  reduce lesion scores and improve performance and
  health of birds challenged with E.maxima

9
Floorpen trials Clinacox
10
Mean total lesion scores (MTLS), average live
weight(ALW) and feed conversion (FCR) of
broilers artificially infected with Eimeria
species (17 pooled floorpen trials).
Clinacox 17 pooled floor pen trials

• day 28 day 42 MTLS
• ALW FCR ALW FCR d21 d28
• IUC 877b 1.836a 1.710b 2.028a 4.17a 1.89a
• diclazuril 1 ppm 995a 1.638c 1.827a 1.913b 0.39c
  0.01b
• ref. products 970a 1.751b 1.779a 1.987a 1.06b 0.
  39b

11
Floor pen trials with shuttle programsUSA,
McDougald-1991

• - duration 45 days
• - shuttle on day 21
• - treatment and infection
• diclazuril in starter and challenge on day 15
• diclazuril in grower and challenge on day 21
• - lesion scores 7 days post infection
• - litter oocyst counts
• - average liveweight, feed conversion and
  mortality

12
Anticoccidial efficacy of shuttle programs with
diclazurilin the starter phase. Mc Dougald -
1991
Challenge with mixed inoculum on day 15

• starter grower Nr of Average
  Feed MTLS
• treatment treatment repl. pens FBW
  (g) conversion
• DICLAZURIL lasalocid 18 2024 1.895 2.29
• DICLAZURIL salinomycin 18 2016 1.895 1.86
• DICLAZURIL narasin 18 2016 1.896 1.78
• DICLAZURIL monensin 18 2003 1.899 1.77
• nicarbasin salinomycin 18 1993 1.905 2.10
• maduramycin salinomycin 18 1974 1.935 4.06
• halofuginone salinomycin 18 1967 1.940 5.17
• IUC IUC 18 1900 2.027 6.86

13
Anticoccidial efficacy of shuttle programs with
diclazurilin the grower phase. Mc.Dougald - 1991
Challenge with mixed inoculum on day 21

• starter grower Nr of Average
  Feed MTLS
• treatment treatment repl. pens FBW conversion
• salinomycin DICLAZURIL 18 1946 1.901 1.81
• Maxiban DICLAZURIL 18 1935 1.904 1.76
• monensin DICLAZURIL 18 1917 1.911 1.54
• nicarbazin DICLAZURIL 18 1912 1.919 1.78
• salinomycin lasalocid 18 1911 1.920 4.29
• Maxiban narasin 18 1877 1.930 6.18
• nicarbazin salinomycin 18 1877 1.933 4.68
• IUC IUC 18 1828 2.053 8.39

14
Anticoccidial efficacy of shuttle programs with
diclazurilin the starter phase. Conway, 2001 -
published
Challenge with mixed inoculum on day 15

• starter grower Nr of Average
  Feed MTLS
• treatment treatment repl. pens FBW
  (g) conversion
• DICLAZURIL salinomycin 10 2.250a 1.847d 1.63c
• nicarbasin salinomycin 10 2.201b 1.876cd 1.90c
• Maxiban salinomycin 10 2.175b 1.903bc 3.53b
• zoalene salinomycin 10 2.113c 1.921b 6.50a
• IUC IUC 10 2.035d 2.017a 6.40a

15
Anticoccidial efficacy of shuttle programs with
diclazurilin the grower phase. Conway et al.
2001 published
Challenge with mixed inoculum on day 22

• starter grower Nr of Average
  Feed MTLS
• treatment treatment repl. pens FBW conversion
• salinomycin DICLAZURIL 10 2.156c 1.856c 2.90c
• salinomycin salinomycin 10 2.023a 1.913b 9.50
  a
• salinomycin monensin 10 2.012b 1.914b 9.90a
• salinomycin lasalocid 10 2.037b 1.936b 8.46b
• IUC IUC 10 1.921b 1.994a 10.05a

16
The field situation
17
Clinacox field trial results
225 broiler flocks4.7 million broilers

• The Netherlands
• United Kingdom
• France
• Germany
• Belgium

18
Clinacox field trial results

• Direct house to house comparisons
• Coccidiosis control
• Lesion scores
• OPG counts
• Broiler performance
• ADG
• FCR
• EBI

19
Clinacox field trial results

• Netherl. nicarb/salinomycin ltgt nicarb/CLINACOX
• France nicarb/salinomycin ltgt
  ionoph/CLINACOX ionophore full ltgt
  ionoph/CLINACOX
• U.K. Maxiban/ionoph. ltgt CLINACOX/ionoph.
• Belgium nicarb/monensin ltgt CLINACOX full
• Germany nicarb/monensin ltgt CLINACOX
  full salinomycin full ltgt CLINACOX full

20
Broiler performance The Netherlands
The Netherlands nicarbazin / Clinacox nicarbazin
/ salinomycin
FBW (g)
ADG
EBI
Adj FCR
Clinacox
Clinacox
Clinacox
Clinacox
1839
45.1
243
1.654
1815
44.4
236
1.683
Reference
21
Broiler performance Belgium
Belgium Clinacox full nicarbazin / monensin
FBW (g)
ADG
EBI
Adj FCR
Clinacox
Clinacox
Clinacox
Clinacox
1771
43.3
234
1.720
1717
41.6
219
1.770
Reference
22
Broiler performance U.K.
U.K. Clinacox / ionophore maxiban / ionophore
FBW (g)
ADG
EBI
Adj FCR
Clinacox
Clinacox
Clinacox
Clinacox
2237
49.9
241
1.666
2147
47.9
223
1.767
Reference
23
Broiler performance France
France ionophore (d26) / Clinacox nicarbazin /
salinomycin or ionophores full
FBW (g)
ADG
EBI
Adj FCR
Clinacox
Clinacox
Clinacox
Clinacox
1676
41.5
208.4
1.821
1666
41.6
205.9
1.841
Reference
24
Broiler performance Germany
Germany Clinacox full salinomycin full
FBW (g)
ADG
EBI
Adj FCR
Clinacox
Clinacox
Clinacox
Clinacox
1454
40.0
205.5
1.852
1441
38.7
194.8
1.906
Reference
25
Broiler performance Total pool
Total trial pool 4.7 million broilers 225 crops
Clinacox
Clinacox
Clinacox
Clinacox
1795
44.0
226.3
1.743
1757
42.8
215.7
1793
Reference
26
Conclusion

• Clinacox advantageous in each type of programme
• Optimal results when Clinacox in full programme
  or in 2nd phase of the shuttle
• Improved coccidiosis control better performance
• Average improvement was 10.6 points EBI

27
The field situation Sensitivity test UK

• Anticoccidial drug sensitivity test UK , 1996
• 9 top broiler integrations UK
• 5 farms per integration
• 5 houses per farm
• 10 mixed feaces samples per house
• Evaluation
• Lesion scores
• Oocyst counts
• Weight gains

28
Sensitivity test UK , 1996

• Sensitive gt 50 reduction vs IUC
• Reduced sensitivity 30 lt RS lt 50 reduction
  vs IUC
• Resistance lt 30 reduction vs IUC

29
Anticoccidial drug sensitivity survey UK 1996
Evaluation of 9 sensitivity tests in the UK
Average lesion score in small intestine and
reduction vs IUC
ionophores
synthetical
50 39 37 39 42 31 46 39 79 37 50 50 50 50
reduction vs IUC
30
Evaluation of 9 sensitivity tests in the UK
Sensitivity profile for intestinal coccidiosis
9
8
7
6
5
4
3
2
1
1
31
Evaluation of 9 sensitivity tests in the UK
Average lesion score in the caecum and
reduction vs IUC
ionophores
synthetical
37 21 25 17 25 25 59 67 67 71 80 75 46 71
reduction vs IUC
32
Evaluation of 9 sensitivity tests in the UK
Sensitivity profile for caecal coccidiosis
33
Evaluation of 9 sensitivity tests in the UK
Oocyst per gram (x1000) on d 6 and d 7 and
reduction vs IUC
ionophores
synthetical
16 10 10 16 30 9 35 52 65 38 52 32 35 62
reduction vs IUC
34
Evaluation of 9 sensitivity tests in the UK
Weight gain days -2 to 7 as of UUC
synthetical
ionophores
64 55 57 58 54 52 67 64 81 58 67 65 71 74
of UUC
35
Sensitivity test UK , 1996

• Conclusions
• 4 years after launch !!
• very good efficacy against E. Tenella
• moderate activity against E.acervulina
• Efficacy profile varies per integration/farm

36
Clinacox in turkeys

• Battery trials
• Broad spectrum E.Adenoides
  E.Gallopavonis E.Melegrimitis
  E.Dispersa
• Potent activity No lesions No oocyst
  excretion
• 1 ppm is sufficient

37
Floorpen trials - BELGIUM Average live weight
on day 35 and 49
38
Floorpen trials - ITALY - Average Live Weights
(Means of males and females)
39
Floorpen trials - SPAIN - Average live weight
40
Floorpen trials - GERMANY - Average live
weights
41
Floorpen trials - UNITED KINGDOM - Average
live weights in grams () at the end of the trial
(day 98)
42
Field trial results Summary
43
Clinacox in turkeys

• Conclusions
• Excellent coccidiosis control
• Performance of Clinacox groups superior,even at
  end of the grow-out
• Safe, no side effects
• No incompatibilities

44
Efficacy of Clinacox in other animal spp.

• Pheasant and partridges (V7179 V7913 V7972
  V8223 V8316 V8318 V8772 8372)
• diclazuril effective against all tested E.spp
• 1 ppm not sufficient
• 2 to 4 ppm required for full efficacy
• Ducks (V8077)
• 1 ppm effective agains most common. E.spp
• Guinea fowl (V8341)
• 1 ppm effective agains most common. E.spp

45
Clinacox in rabbits

• 1 ppm dose effective to prevent
• intestinal coccidiosis
• liver coccidiosis

46
Influence of diclazuril on oocyst
sporulation(Löwenstein et al., 1989)
preparation age of infected maduramycin
diclazuril cultures cultures on control 5
ppm 1 ppm days p.i. counts (hrs)
5 144 75.7 (100) 85.4 (112.8) - -
6 120 70.4 (100) 65.8 (93.5) 45.2 (64.2)
7 96 68.0 (100) 60.8 (89.4) 30.8 (45.3)
8 96 65.7 (100) 76.4 (116.3) 20.8 (31.7)
9 96 62.9 (100) 59.8 (95.1) 38.2 (60.7) 10 96 63.
1 (100) 45.9 (72.7) 21.0 (33.3) 11 72 61.2 (100)
55.1 (90.0) - - 12 168 80.3 (100) 57.4 (71.5
) - -
(-) no oocysts shed.
47
Clinacox residual activity(L. Mc Dougald, USA
Published Vet. Parasitology V 7672)
48
Effect on natural immunity development
Laboratory trial conducted by Dr. Louis Maes
at janssen Pharmaceutica, 1994
49
Ccoccidiosis immunisation trial
Daily tricle infectionswith low doses of coccidia
High challenge dose
3 weeks of age
5 weeks of age
14 days
50
Coccidiosis immunisation trial

• 3 groups
• group 1 Not immunized with trickle infection
• Group 2 Immunized with trickle infection
• Group 3 Immunized and treated with Clinacox

51
Eimeria tenella Body weight evolution

• Trickle infections 5 times 2000 oocysts
• Challenge infection 200.000 oocysts

Day/p.I.
52
Eimeria acervulina challenge BW
Non-medicated birds,immunised with trickle
infections Birds with diclazuril 1 ppm
andimmunised with trickle infections Non-medicate
d,non immunised control birds

• Trickle infections 3 times 1000 oocysts
• Challenge infection 2000.000 oocysts

53
Eimeria necatrix challenge BW
Non-medicated birds,immunised with trickle
infections Birds with diclazuril 1 ppm
andimmunised with trickle infections Non-medicate
d,non immunised control birds

• Trickle infections 3 times 100 oocysts
• Challenge infection 10.000 oocysts

54
Eimeria brunetti challenge BW
Non-medicated birds,immunised with trickle
infections Birds with diclazuril 1 ppm
andimmunised with trickle infections Non-medicate
d,non immunised control birds

• Trickle infections 3 times 100 oocysts
• Challenge infection 200.000 oocysts

55
Eimeria maxima challenge BW
Non-medicated birds,immunised with trickle
infections Birds with diclazuril 1 ppm
andimmunised with trickle infections Non-medicate
d,non immunised control birds

• Trickle infections times 20 oocysts
• Challenge infection 500.000 oocysts

56
Clinacox and natural immunity formation
conclusions

• Site of action suggest little chance for negative
  interference
• Experiments confirm
• even when fully sensitive strains are used no
  negative interference with immunity.
• Imunity can develop even when chickens do not
  excrete many oocysts

57
Clinacox efficacy profile A unique anticoccidial

• Exceptional low dose
• Potent
• strong reduction of oocyst excretion and lesions
• Broad spectrum
• effective against all Eimeria spp. , in all
  poultry spp
• Cidal action
• intestinal stages are killed
• Oocidal
• 50 of oocysts produced during treatment are not
  viable
• Residual activity
• coccidiosis protection up to 5 days after drug
  withdrawal
• No negative impact on immunity development
• Low infection pressure sufficient to stimulate
  immunity