Sarolaner, moxidectin, and pyrantel chewable tablets: what the FDA reviewed for dog products

Simparica TRIO® NADA 141-521, Supplemental approval, April 08, 2025; sponsor Zoetis Inc.; species: Dogs; foi_id 16785; FDA PDF

Indication

Supplement adds prevention of Dipylidium caninum (tapeworm) infections as a direct result of killing Ctenocephalides felis vector fleas on the treated dog for one month, in dogs and puppies 8 weeks of age and older and 2.8 pounds or greater.

Dose regimen

sarolaner 0.54 mg/lb (1.2 mg/kg), moxidectin 0.011 mg/lb (24 μg/kg), pyrantel 2.27 mg/lb (5 mg/kg), oral, once a month, dose unchanged by this supplement

This supplemental approval does not change the previously approved doses of sarolaner (0.54 mg/lb; 1.2 mg/kg), moxidectin (0.011 mg/lb; 24 μg/kg), and (pyrantel 2.27 mg/lb; 5 mg/kg) (as pamoate salt), given orally once a month.

Effectiveness

Placebo-controlled, masked, randomized complete block laboratory dose confirmation study A166C-US-22-C41 (GCP): single oral Simparica TRIO on Day 0 vs Pet-Tabs control, 10 dogs per group; ~200 D. caninum-infected C. felis fleas applied on Days 0, 7, 14, 21, 30; flea counts Day 33; necropsy scolex counts Day 58; n = Twenty (10 per group); primary endpoint: Percent effectiveness vs control in geometric mean D. caninum scolex count at Day 58 (and LSM flea count at Day 33); result: 100% effectiveness for prevention of D. caninum infection (control GM 15.9 vs 0; p<0.0001) and 100% against fleas (LSM 67.0 vs 0)

Study Animals: Twenty beagle and mixed-breed dogs (10 males and 10 females), 20 to 50 months of age, and 7.3 to 14.5 kg body weight.

Adverse reactions

Extraction notes: Supplemental approval (April 8, 2025) for tapeworm prevention via flea killing; no PK. 'FDA did not require target animal safety studies for this supplemental approval.' Two laboratory studies of 20 dogs each (10 per group): A166C-ZA-22-C42 (South Africa; 100% flea effectiveness, 92.1% D. caninum prevention, control GM scolex 5.2 vs 0.4, one control dog excluded for incorrect dosing; one treated dog had diarrhea) and A166C-US-22-C41 (recorded here). Result quotes: 'There was a significant difference in mean scolex counts (p<0.0001) for Simparica TRIO®-treated dogs compared to the control group, demonstrating 100% effectiveness for the prevention of D. caninum infection.'; Table II.6 '15.9 0 100%' (control GM, treated GM, % effectiveness); Table II.5 '67.0 0 100%'. US study adverse reactions: 'No adverse reactions were observed during the study.' Note the source dose sentence has misplaced parentheses around pyrantel.

Simparica TRIO® NADA 141-521, Supplemental approval, December 23, 2021; sponsor Zoetis Inc.; species: Dog; foi_id 11809; FDA PDF

Indication

Supplement adds prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks, and treatment and control of L4 and immature adult Ancylostoma caninum (to existing heartworm, roundworm/hookworm, flea and tick indications).

Dose regimen

minimum 0.54 mg/lb (1.2 mg/kg) sarolaner, 0.011 mg/lb (24 μg/kg) moxidectin, and 2.27 mg/lb (5 mg/kg) pyrantel, oral (chewable tablet), once a month, dosage unchanged by this supplement

Simparica TRIO® is given orally, once a month, at the recommended minimum dose of 0.54 mg.lb (1.2 mg/kg) sarolaner, 0.011 mg/lb (24 μg/kg) moxidectin, and 2.27 mg/lb (5 mg/kg) pyrantel (as pamoate salt).

Effectiveness

Placebo-controlled, masked, randomized laboratory dose confirmation study A166C-US-20-B31 (GCP): single oral Simparica TRIO (1.2 mg/kg sarolaner, 24 μg/kg moxidectin, 5 mg/kg pyrantel) on Day 0 vs placebo, 10 dogs per group; infestation with ~50 wild-caught adult I. scapularis (80% B. burgdorferi infection rate) on Day 28; tick counts Day 33; serology (SNAP 4Dx Plus, Lyme Quant C6) and skin PCR through Day 104; n = 20 (10 per group); primary endpoint: B. burgdorferi infection status (serology and PCR) and live tick count reduction on Day 33; result: 100% reduction in live ticks on Day 33; 9 of 10 treated dogs remained uninfected vs 9 of 9 placebo dogs infected (P = 0.0001)

Study Animals: Twenty (20) Beagle dogs (15 male and 5 female), 10-11 months of age, and 3.3 to 5.5 kg body weight.

Extraction notes: Supplemental approval (December 23, 2021) adding Lyme prevention and L4/immature adult A. caninum indications; no PK. 'CVM did not require target animal safety studies for this supplemental approval.' Six laboratory dose-confirmation studies (two Lyme transmission-blocking studies of 20 Beagles each; four A. caninum L4/immature adult studies of 16-18 dogs each); the first Lyme study is recorded. Result quotes: 'The percent reduction in arithmetic mean live tick counts in the Simparica TRIO®-treated group compared to the placebo group on Day 33 was 100%.' and 'Nine of ten Simparica TRIO®-treated dogs were determined to not have been infected with B. burgdorferi by remaining seronegative throughout the study ... indicating prevention of B. burgdorferi infection.' One treated dog had three positive Lyme Quant C6 tests and a low positive PCR on one of four biopsies. Adverse reactions: 'There were no treatment-related adverse reactions during the study.' n_dogs '10 per group' derives from the text 'two treatment groups of 10 dogs per group'; the dose quote contains the source typo 'mg.lb'.

Simparica TRIO® NADA 141-521, Supplemental approval, November 06, 2024; sponsor Zoetis Inc.; species: Dogs; foi_id 16065; FDA PDF

Indication

Supplement adds treatment and control of Haemaphysalis longicornis (Asian longhorned tick) infestations for one month in dogs and puppies 8 weeks of age and older and 2.8 pounds or greater.

Dose regimen

sarolaner 0.54 mg/lb (1.2 mg/kg), moxidectin 0.011 mg/lb (24 μg/kg), pyrantel 2.27 mg/lb (5 mg/kg), oral, once a month, dose unchanged by this supplement

This supplemental approval does not change the previously approved doses of sarolaner (0.54 mg/lb; 1.2 mg/kg), moxidectin (0.011 mg/lb; 24 μg/kg), and pyrantel (2.27 mg/lb; 5 mg/kg) (as pamoate salt), given orally once a month.

Effectiveness

Negative-controlled, masked, randomized complete block laboratory dose confirmation study A162C-US-22-C80 (GCP): single oral SimparicaTRIO (1.2 mg/kg sarolaner + 24 μg/kg moxidectin + 5 mg/kg pyrantel) on Day 0 vs Pet-Tabs control, 10 dogs per group; ~50 adult H. longicornis infestations on Days -2, 7, 14, 21, 30; live/dead tick counts 48 h later (Days 2, 9, 16, 23, 32); n = Twenty (10 per group); primary endpoint: Percent reduction in arithmetic mean live tick counts vs control at each count day; result: 100% effectiveness at every count (Days 2-32); no live ticks on any treated dog for 32 days; control means 13.1-31.4

Study Animals: Twenty Beagle dogs (10 males and 10 females), 10 to 15 months of age, and 5.8 to 9.9 kg body weight.

Extraction notes: Supplemental approval (November 6, 2024) for Asian longhorned tick; no PK or new target animal safety studies (TAS section refers to the original NADA 141-521 FOI summary; the section text 'CVM did not require target animal safety studies' could not be retrieved via grep). Two laboratory studies (A162C-US-22-C80 and A162C-ZA-22-C81, 20 dogs each, 10 per group); the US study is recorded. Result quotes: 'There were no live ticks on any dog administered SimparicaTRIO® for 32 days after dosing.' and Table II.2 '2 13.1 0.0 100% 9 15.0 0.0 100% 16 31.4 0.0 100% 23 29.7 0.0 100% 32 27.1 0.0 100%' (day, control mean, treated mean, % effectiveness). The South Africa study gave 100%, 100%, 99.6%, 100%, 99.7%. Adverse reactions: 'No adverse reactions were observed during the study.' n_dogs '10 per group' is from the design text (Table II.1 Dogs per Group 10).