Oclacitinib: what the FDA reviewed for dog products
2 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Oclacitinib, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- apoquel® (NADA/ANADA 141-345)
- apoquel® chewable (NADA/ANADA 141-555)
apoquel® chewable NADA 141-555, Original approval, June 09, 2023; sponsor Zoetis Inc.; species: Dogs; foi_id 14146; FDA PDF
Indication
Control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age.
Dose regimen
0.18 to 0.27 mg oclacitinib/lb (0.4 to 0.6 mg oclacitinib/kg), oral (chewable tablet), twice daily for up to 14 days, then once daily, once daily for maintenance therapy after the initial up-to-14-day twice-daily period
The dose of apoquel® chewable (oclacitinib chewable tablet) is 0.18 to 0.27 mg oclacitinib/lb (0.4 to 0.6 mg oclacitinib/kg) body weight, administered orally, twice daily for up to 14 days, and then administered once daily for maintenance therapy.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | AUC0-t(last) 2420 ng*h/mL (oclacitinib film-coated tablet) and 2500 ng*h/mL (apoquel chewable), geometric means | single oral 5.4 mg tablet, fasted, 42 male Beagles, two-period crossover (Study A461N-US-21-B66) | Overall exposure was similar between the groups with mean AUC0-t(last) of 2420 and 2500 ng*h/mL for oclacitinib FCT and apoquel® chewable, respectively. |
| auc | AUC0-inf 2470 ng*h/mL (FCT); 2570 ng*h/mL (chewable), geometric means | single oral 5.4 mg tablet, fasted, 42 male Beagles | AUC0-∞ (ng*h/mL) Oclacitinib FCT 42 2470 1060 4760 apoquel® chewable 42 2570 1180 5470 |
| cmax | 339 ng/mL (FCT); 292 ng/mL (chewable), geometric means | single oral 5.4 mg tablet, fasted, 42 male Beagles | Cmax (ng/mL) Oclacitinib FCT 42 339 166 571 apoquel® chewable 42 292 89.9 565 |
| half-life | 5.28 hours (FCT); 5.70 hours (chewable) | single oral 5.4 mg tablet, fasted, 42 male Beagles | The mean t1/2 was also similar across groups with mean values of 5.28 and 5.70 hours for oclacitinib FCT and apoquel® chewable, respectively. |
| tmax | 1.2 h (FCT); 1.5 h (chewable), LS means | single oral 5.4 mg tablet, fasted, 42 male Beagles | tmax (h) Oclacitinib FCT 42 1.2 0.33 2.5 apoquel® chewable 42 1.5 0.67 2.5 |
| other | bioequivalence ratios chewable/FCT: AUC0-t(last) 1.03 (CI 0.98, 1.08) passed; Cmax 0.86 (CI 0.78, 0.95) failed | single oral 5.4 mg tablet, acceptance limits 0.80-1.25 | AUC0-t(last) 1.03 0.98, 1.08 Yes Cmax 0.86 0.78, 0.95 No |
Effectiveness
PK bridge to apoquel (NADA 141-345): GLP two-sequence, two-treatment, two-period crossover bioequivalence study (Study A461N-US-21-B66) in 42 fasted male Beagles, single 5.4 mg tablet, 14-day washout; plus repeated-dose simulations, comparative dissolution of 3.6/5.4/16 mg tablets, and a 121-dog palatability study. No clinical effectiveness study; n = 42 male Beagles (BE study); primary endpoint: Bioequivalence of AUC0-t(last) and Cmax (90% CI of geometric mean ratio within 0.80-1.25); result: AUC0-t(last) bioequivalent (ratio 1.03); Cmax not bioequivalent (lower 90% CI 0.78); FDA accepted the weight of evidence as a bridge to apoquel effectiveness and safety
Study Animals: 42 male Beagle dogs were enrolled. The dogs ranged from 13 to 35 months of age and weighed 7.1 to 12.0 kg body weight.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (uncontrolled palatability study, 120 dogs) | 2 | Five dogs experienced seven adverse reactions during the study which included an accidental overdose (1), lethargy (1), and GI distress (flatulence (1), diarrhea (2) and vomiting (2)). | |
| Vomiting (uncontrolled palatability study, 120 dogs) | 2 | Five dogs experienced seven adverse reactions during the study which included an accidental overdose (1), lethargy (1), and GI distress (flatulence (1), diarrhea (2) and vomiting (2)). | |
| Lethargy (uncontrolled palatability study, 120 dogs) | 1 | Five dogs experienced seven adverse reactions during the study which included an accidental overdose (1), lethargy (1), and GI distress (flatulence (1), diarrhea (2) and vomiting (2)). |
Extraction notes: No target animal safety study: safety is bridged to apoquel (NADA 141-345, May 14, 2013) via the BE study, so target_animal_safety is null. The 'effectiveness' block records the BE/weight-of-evidence bridge that fills the Substantial Evidence section; no placebo-controlled effectiveness trial was run. Adverse reactions are from the single-arm palatability study (no control group) and the BE study reported none. Corrected FOI summary (July 21, 2023 corrections to study days and exclusion wording).
apoquel® NADA 141-345, Original approval, May 14, 2013; sponsor Zoetis Inc.; species: Dogs; foi_id 902; FDA PDF
Indication
Control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age.
Dose regimen
0.18 to 0.27 mg oclacitinib/lb (0.4 to 0.6 mg oclacitinib/kg), oral (tablet), twice daily for up to 14 days, then once daily, once daily for maintenance therapy after the initial up-to-14-day twice-daily period
The dose of APOQUEL (oclacitinib maleate) tablets is 0.18 to 0.27 mg oclacitinib/lb (0.4 to 0.6 mg oclacitinib/kg) body weight, administered orally, twice daily for up to 14 days, and then administered once daily for maintenance therapy.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| protein binding | 66.3-69.7% bound | fortified canine plasma, 10-1000 ng/mL | The oclacitinib protein binding was low with 66.3-69.7% bound in fortified canine plasma at nominal concentrations ranging from 10-1000 ng/mL. |
| auc | 953 ng·hr/mL (CI 713, 1275) (AUC0-inf) | 0.282 mg/kg intravenous, dogs (least square mean) | Area under the plasma concentration-time curve from 0 and extrapolated to infinity (AUC0-∞), ng∙hr/mL 953 (713, 1275) |
| half-life | 3.45 hours (CI 2.21, 4.68) | 0.282 mg/kg intravenous | Terminal Plasma elimination half-life (T1/2), hours 3.45 (2.21, 4.68) |
| clearance | 316 mL/h/kg (CI 237, 396) (CLtotal) | 0.282 mg/kg intravenous | CLtotal, mL/h/kg 316 (237, 396) |
| other | Vdss 942 mL/kg (CI 870, 1014) | 0.282 mg/kg intravenous | Vdss, mL/kg 942 (870, 1014) |
| cmax | 259 ng/mL (CI 189, 355), normalized to 0.4 mg/kg | 0.4 to 0.6 mg/kg oral dose, dogs (least square mean) | Maximum concentration normalized to 0.4 mg/kg, (Cmax), ng/mL 259 (189, 355) |
| tmax | 0.9 hours (CI 0.46, 1.34) | 0.4 to 0.6 mg/kg oral dose | Time of maximum concentration (Tmax), hours 0.9 (0.46, 1.34) |
| auc | 1206 ng·hr/mL (CI 909, 1599), AUC0-inf normalized to 0.4 mg/kg | 0.4 to 0.6 mg/kg oral dose | AUC0-∞ normalized to 0.4 mg/kg, ng∙hr/mL 1206 (909, 1599) |
| half-life | 4.13 hours (CI 3.08, 5.19) | 0.4 to 0.6 mg/kg oral dose | T1/2, hours 4.13 (3.08, 5.19) |
| bioavailability | 89% (CI 85%, 94%) | oral, 0.4 to 0.6 mg/kg vs IV | Bioavailability 89% (85%, 94%) |
Target-animal safety
dose multiples 1X (0.6 mg/kg), 3X (1.8 mg/kg), 5X (3 mg/kg); duration 26 weeks: twice daily for 6 weeks, then once daily for 20 weeks (Study A29); animals sixteen male and sixteen female Beagles (eight per group, four per sex).
To evaluate the margin of safety of oclacitinib maleate administered orally in dogs at 1, 3, and 5 times maximum exposure dose of 0.6 mg/kg oclacitinib twice daily (BID) for 6 weeks, then once daily (SID) for 20 weeks. b. Study Animals: Sixteen male and sixteen female Beagle dogs approximately 12 months of age weighing between 6.7 and 9.9 kg
| Finding | Quote |
|---|---|
| Dose-dependent interdigital furunculosis (cysts) with dermatitis and peripheral lymphadenopathy | Clinical observations that were considered likely to be related to oclacitinib maleate included a dose-dependent increase in the number and frequency of interdigital furunculosis (cysts) on one or more feet during the study. |
| Papillomas considered treatment related (0X none, 1X 4 dogs, 3X 2 dogs, 5X 4 dogs) | Papillomas were also considered treatment related due to incidence in placebo 0X (no dogs), 1X (4 dogs), 3X (2 dogs), and 5X (4 dogs). |
| Mild dose-dependent reductions in hematocrit, hemoglobin, reticulocytes (5X mean below reference range) and lymphocytes, eosinophils, basophils | Clinical pathology findings considered to be oclacitinib maleate-related included a mild, dose-dependent reduction in hematocrit, hemoglobin, and reticulocyte counts during the twice daily dosing period (the mean of the 5X group dropped below the lower limit of the reference range) with a decrease in leukocyte subsets of lymphocytes, eosinophils, and basophils. |
| Lymphoid depletion in GALT, spleen, thymus, lymph nodes and bone marrow | Direct oclacitinib maleate-related microscopic findings included decreased cellularity (lymphoid) in Gut-Associated Lymphoid Tissue (GALT), spleen, thymus, and cervical and mesenteric lymph node; decreased cellularity of sternal and femoral bone marrow; |
| Mild interstitial pneumonia in five treated dogs | Five oclacitinib maleate-treated dogs had evidence of mild interstitial pneumonia on microscopic examination. |
| Earlier chronic study in 6-month-old dogs stopped at 4 months for immunosuppression (pneumonia, demodicosis) at 3X and 5X | That safety study was discontinued after four months because clinical evidence of immunosuppression, including bacterial pneumonia and generalized demodex mange infections, was observed in the high dose (3X and 5X) treatment groups (1.8 and 3.0 mg/kg BID). |
| Vaccine response study (3X BID, 12 weeks, puppies): two deaths from infection secondary to immunosuppression | Infection secondary to immunosuppression resulted in two deaths, including one death that occurred 28 days after discontinuation of oclacitinib maleate. |
Effectiveness
Study 930: masked, multi-site (26 US sites), placebo-controlled field study of oclacitinib 0.4-0.6 mg/kg BID for pruritus associated with allergic dermatitis (Study Phase Days 0-7, continuation to Day 28); 436 dogs enrolled (216 oclacitinib, 220 placebo). Study A16: masked, multi-site, placebo-controlled 112-day study for atopic dermatitis (BID 14 days then SID); 299 dogs (152 oclacitinib, 147 placebo); n = 203 oclacitinib and 204 placebo dogs evaluable for the pruritus-study primary endpoint; primary endpoint: Study 930: proportion of treatment successes (>= 2 cm decrease from baseline on 10 cm owner pruritus VAS on at least 5 of Days 1-7). Study A16: success at Day 28 for owner pruritus VAS (>= 2 cm decrease) and investigator CADESI-02 (>= 50% decrease); result: Study 930: success proportion 0.67 oclacitinib vs 0.29 placebo (p < 0.0001). Study A16: pruritus VAS success 0.66 vs 0.04 and CADESI-02 success 0.49 vs 0.04 (both p < 0.0001)
Placebo n = 204 60 0.29 0.23 to 0.36 Oclacitinib Maleate n = 203 135 0.67 b 0.59 to 0.73
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (Study 930, Days 0-7) | 5/216 (2.3%) | 2/220 (0.9%) | Oclacitinib Maleate Group Number (%) of Dogs n = 216 Placebo Group Number (%) of Dogs n = 220 Diarrhea 5 (2.3) 2 (0.9) Vomiting 5 (2.3) 4 (1.8) Lethargy 4 (1.8) 3 (1.4) Anorexia 3 (1.4) 0 (0.0) Polydipsia 3 (1.4) 0 (0.0) |
| Vomiting (Study 930, Days 0-7) | 5/216 (2.3%) | 4/220 (1.8%) | Oclacitinib Maleate Group Number (%) of Dogs n = 216 Placebo Group Number (%) of Dogs n = 220 Diarrhea 5 (2.3) 2 (0.9) Vomiting 5 (2.3) 4 (1.8) Lethargy 4 (1.8) 3 (1.4) Anorexia 3 (1.4) 0 (0.0) Polydipsia 3 (1.4) 0 (0.0) |
| Lethargy (Study 930, Days 0-7) | 4/216 (1.8%) | 3/220 (1.4%) | Oclacitinib Maleate Group Number (%) of Dogs n = 216 Placebo Group Number (%) of Dogs n = 220 Diarrhea 5 (2.3) 2 (0.9) Vomiting 5 (2.3) 4 (1.8) Lethargy 4 (1.8) 3 (1.4) Anorexia 3 (1.4) 0 (0.0) Polydipsia 3 (1.4) 0 (0.0) |
| Anorexia (Study 930, Days 0-7) | 3/216 (1.4%) | 0/220 (0.0%) | Oclacitinib Maleate Group Number (%) of Dogs n = 216 Placebo Group Number (%) of Dogs n = 220 Diarrhea 5 (2.3) 2 (0.9) Vomiting 5 (2.3) 4 (1.8) Lethargy 4 (1.8) 3 (1.4) Anorexia 3 (1.4) 0 (0.0) Polydipsia 3 (1.4) 0 (0.0) |
| Diarrhea (Study A16, Days 0-16) | 7/152 (4.6%) | 5/147 (3.4%) | n = 152 Placebo Group Number (%) of Dogs n = 147 Diarrhea 7 (4.6) 5 (3.4) Vomiting 6 (3.9) 6 (4.1) Anorexia 4 (2.6) 0 |
| Vomiting (Study A16, Days 0-16) | 6/152 (3.9%) | 6/147 (4.1%) | n = 152 Placebo Group Number (%) of Dogs n = 147 Diarrhea 7 (4.6) 5 (3.4) Vomiting 6 (3.9) 6 (4.1) Anorexia 4 (2.6) 0 |
Extraction notes: Effectiveness quote is the Table 6 row text for Study 930 (n = 203/204 evaluable); Study A16 results (Tables 11-12) are summarized in the result string. TAS n_animals kept in words because the design quote spells out 'Sixteen male and sixteen female'. Additional long-term safety signals (neoplasia, demodicosis, pneumonia) in the open-label continuation study A75 are narrative only and not captured as findings. Adverse reaction tables (Table 8 and Table 16) survived PDF extraction.
Reproduce: foi_structured_search(query="Oclacitinib") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).