Sarolaner: what the FDA reviewed for dog products

SIMPARICA® NADA 141-452, Supplemental approval, December 12, 2016; sponsor Zoetis Inc.; species: Dog; foi_id 103; FDA PDF

Indication

Supplement adds treatment and control of Ixodes scapularis (black-legged tick) infestations for one month in dogs 6 months of age or older weighing 2.8 pounds or greater (in addition to fleas and four other tick species).

Dose regimen

0.91 mg/lb (2 mg/kg), oral (chewable tablet), once per month, dose unchanged from original approval

0.91 mg/lb (2 mg/kg) body weight, once per month

Effectiveness

Two laboratory dose confirmation studies (A166C-US-12-108, 16 dogs; A166C-US-15-608, 20 dogs), vehicle-controlled, masked tick counts; single oral 2.0 mg/kg dose on Day 0 with induced I. scapularis infestations (~50 ticks) on Days -2, 5, 12, 19, 26, 33 and counts 48 h later; n = 16 (8 per group); primary endpoint: percent reduction in geometric mean live tick counts vs control at 48 hours (control) and dead tick counts (treatment); result: Study 108: 100% reduction in live ticks at all counts through Day 35; Study 608: 99.4% initial and at least 99.6% after weekly re-infestations through Day 35 (P<0.0001 vs control)

Study Animals: 16 Beagle and mixed breed dogs (8 male and 8 female), 15 - 78 months of age, weighing between 7.1 - 12.4 kg.

Extraction notes: Supplemental approval; CVM did not require target animal safety studies (target_animal_safety null; see original approval FOI). No adverse reactions were reported in either study. Two-study result summarized in 'result'; n_dogs and quote refer to Study A166C-US-12-108.

SIMPARICA® NADA 141-452, Original approval, February 24, 2016; sponsor Zoetis Inc.; species: Dog; foi_id 940; FDA PDF

Indication

Kills adult fleas; treatment and prevention of flea infestations (Ctenocephalides felis) and treatment and control of tick infestations (Amblyomma americanum, A. maculatum, Dermacentor variabilis, Rhipicephalus sanguineus) for one month in dogs 6 months of age or older weighing 2.8 pounds or more.

Dose regimen

2 mg/kg, oral (chewable tablet), once per month, minimum dosage 2.0 mg/kg selected from dose determination against A. maculatum; tablets 5-120 mg; with or without food

2 mg/kg body weight, once per month

Pharmacokinetics

Target-animal safety

dose multiples 0X, 1X (4 mg/kg), 3X (12 mg/kg), 5X (20 mg/kg); duration 10 oral doses at 28-day intervals (Days 0-252) starting at 8 weeks of age; necropsy Day 259; animals 32 (16 male and 16 female).

32 healthy beagle puppies (16 male and 16 female), age 56-59 days at Day 0.

Effectiveness

Masked, multi-center (19 US sites), randomized-block field study A161C-US12-074 vs active control spinosad in client-owned dogs with natural flea infestations; treatments on Days 0, 30 and 60; flea counts on primary dogs Days 14, 30, 60, 90; n = 315 sarolaner and 164 spinosad for safety; 186 sarolaner and 96 spinosad for Day 30 effectiveness; primary endpoint: percent reduction in geometric mean live flea counts on primary dogs vs Day 0; result: Sarolaner 99.2% reduction at Day 14 and >99.4% from Day 30 to Day 90 (100% at Day 90); spinosad 97.1% at Day 14 and >94.9% thereafter; 87.7-100% of sarolaner dogs improved in flea allergy dermatitis signs by Day 90

315 sarolaner-treated dogs and 164 spinosad-treated dogs were evaluated for safety. The effectiveness analysis for Day 30 was performed on 186 sarolaner-treated dogs and 96 spinosad-treated dogs.

Adverse reactions

Extraction notes: Adverse-reaction rows quoted as extracted from Table 32 of the flea field study (column order: term, sarolaner N (%) of 315, spinosad (active control) N (%) of 164); 'control' column is the spinosad comparator, not placebo. One sarolaner dog had lethargy, ataxia, elevated third eyelids and inappetence one day after dosing concurrently with ivermectin/pyrantel. Effectiveness section also contains eight laboratory tick dose-confirmation studies (16 dogs each; 96.9-100% reduction in live ticks through Day 35 for A. americanum, A. maculatum, D. variabilis, R. sanguineus), two flea laboratory studies (100% through Day 35; simulated home environment), speed-of-kill (at least 96.2% by 8 h) and egg-production studies. PK statement comes from the margin-of-safety study, not a dedicated PK study.

SIMPARICA® NADA 141-452, Supplemental approval, May 18, 2021; sponsor Zoetis Inc.; species: Dogs; foi_id 10860; FDA PDF

Indication

Supplement adds prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks (existing flea and tick indications unchanged).

Dose regimen

2 mg/kg, oral (chewable tablet), once per month, dose unchanged from original approval (0.91 mg/lb)

2 mg/kg body weight, once per month

Effectiveness

Two placebo-controlled, masked, randomized laboratory studies (A162C-US-19-A71, A162C-US-19-A74; 20 Beagles each, 10 per group); single oral dose of 2.0 mg/kg on Day 0, infestation with ~50 wild-caught B. burgdorferi-infected I. scapularis on Day 28 (60% and 75% infection rate), tick counts Day 33, serology (SNAP 4Dx Plus, Lyme Quant C6) through Day 104 and skin-biopsy PCR on Day 104; n = 20; primary endpoint: proportion of dogs infected with B. burgdorferi (serology after Day 28 or skin PCR Day 104), Fisher's exact test; live tick reduction Day 33; result: Study A71: 96.5% reduction in live ticks Day 33; 0/10 Simparica dogs vs 9/10 placebo dogs infected (P = 0.0001). Study A74: 100% tick reduction; 0/10 vs 10/10 infected (P < 0.0001). Both concluded 100% prevention of B. burgdorferi infection

Study Animals: Twenty (20) Beagle dogs (11 male and 9 female), 11 months of age, and 7.7 to 12.2 kg body weight

Extraction notes: Supplemental approval; CVM did not require target animal safety studies (target_animal_safety null). No treatment-related adverse reactions in either study (20 dogs received the labeled dose). n_dogs and quote refer to Study A162C-US-19-A71; Study A74 enrolled 20 Beagles (8 male, 12 female, 9 months, 5.1-8.7 kg).

SIMPARICA® NADA 141-452, Supplemental approval, November 22, 2024; sponsor Zoetis Inc.; species: Dogs; foi_id 16325; FDA PDF

Indication

Supplemental indication: treatment and control of Haemaphysalis longicornis (Asian longhorned tick) infestations for one month in dogs 6 months of age or older and weighing 2.8 pounds or greater.

Dose regimen

2 mg/kg (0.91 mg/lb), oral, once a month, Dose unchanged from original approval; in the laboratory studies dogs were fasted 12 hours before a single dose on Day 0

This supplemental approval does not change the previously approved 2 mg/kg (0.91 mg/lb) dose, given orally once a month.

Effectiveness

Two negative-controlled, masked, randomized complete block laboratory dose-confirmation studies (A162C-US-22-C80, Waverly NY, 20 Beagles; A162C-ZA-22-C81, Bloemfontein South Africa, 20 Beagle/mongrel dogs): control (Pet-Tabs) vs single oral SIMPARICA 2 mg/kg on Day 0; ~50 adult H. longicornis infestations on Days -2, 7, 14, 21, 30; live/dead tick counts on Days 2, 9, 16, 23, 32; n = 10 per group; primary endpoint: Percent effectiveness vs control based on arithmetic mean live tick counts 48 hours after treatment or weekly re-infestation; result: US study: 100% reduction in live ticks at every count through Day 32 (P<=0.0001). South Africa study: 100% on Days 2-23 and 99.7% on Day 32 (P<0.0001); dead tick counts higher than control at all counts. Both studies concluded effective for treatment and control for one month.

This study was a negative-controlled, masked, randomized complete block study design. Dogs were randomly assigned to the control group (10 dogs) or the SIMPARICA® group (10 dogs).

Adverse reactions

Extraction notes: Category II supplement adding H. longicornis to the tick claim; no target animal safety studies required (refers to original FOI summary of Feb 24, 2016). Each study enrolled 20 dogs (10 control, 10 SIMPARICA; a Simparica TRIO arm is not presented). Percent effectiveness tables (II.2, II.5) list control arithmetic mean live tick counts 13.1-31.4 vs 0.0-0.1 for SIMPARICA. No PK content in this supplement.