Grapiprant: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Grapiprant, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Galliprant™ (NADA/ANADA 141-455)
Galliprant™ NADA 141-455, Original approval, March 20, 2016; sponsor Elanco US Inc.; species: Dogs; foi_id 941; FDA PDF
Indication
Control of pain and inflammation associated with osteoarthritis in dogs.
Dose regimen
0.9 mg/lb (2 mg/kg), oral (tablet), once daily, pivotal field study dosed for 28 days; food markedly reduces bioavailability (see PK)
The dose of GALLIPRANT (grapiprant tablets) is 0.9 mg/lb (2 mg/kg) once daily.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | food effect: approximately 4.4-fold decrease in Cmax and 2.3-fold decrease in AUC | fed vs fasted, GALLIPRANT tablets (food effect study) | In a previously conducted food effect study, the bioavailability of GALLIPRANT tablets was significantly reduced in the presence of food, with approximately a 4.4-fold and 2.3 fold decrease in Cmax and AUC, respectively, as compared to the fasted condition. |
| auc | 17596 ng*hr/mL (AUC0-last, GALLIPRANT tablets); 13165 ng*hr/mL (methylcellulose suspension) | single oral nominal 6 mg/kg (one 60 mg tablet), Beagles, 2 male/2 female, crossover (Study AT001-CPK-13-010) | AUC0-last ng*hr/mL 17596 13165 1.34 1.10 1.62 |
| cmax | 5020 ng/mL (GALLIPRANT tablets); 3713 ng/mL (suspension) | single oral nominal 6 mg/kg, Beagles, 2 male/2 female | Cmax ng/mL 5020 3713 1.35 1.09 1.68 |
| tmax | 1.297 hr (GALLIPRANT tablets); 1.000 hr (suspension) | single oral nominal 6 mg/kg, Beagles, 2 male/2 female | Tmax hr 1.297 1.000 1.30 1.00 1.68 |
| auc | 436219 ng*hr/mL (AUC0-last, GALLIPRANT tablets); 265774 ng*hr/mL (suspension) | single oral nominal 50 mg/kg (five 100 mg tablets), Beagles, 2 male/2 female | AUC0-last ng*hr/mL 436219 265774 1.64 1.26 2.14 |
| cmax | 97724 ng/mL (GALLIPRANT tablets); 83550 ng/mL (suspension) | single oral nominal 50 mg/kg, Beagles, 2 male/2 female | Cmax ng/mL 97724 83550 1.17 0.94 1.45 |
| tmax | 1.834 hr (GALLIPRANT tablets); 1.122 hr (suspension) | single oral nominal 50 mg/kg, Beagles, 2 male/2 female | Tmax hr 1.834 1.122 1.63 1.09 2.45 |
| other | relative exposure of tablets vs methylcellulose suspension 1.34-1.64 fold higher | bridging PK study, 6 and 50 mg/kg, fasted | Administration of grapiprant as GALLIPRANT tablets to dogs resulted in exposure to grapiprant that was 1.34-1.64 fold higher than the levels of exposure observed when grapiprant was administered as a methylcellulose suspension. |
Target-animal safety
dose multiples 0.12X-0.25X (1 mg/kg suspension), 0.72X-1.48X (6 mg/kg suspension), 4.88X-10.16X (50 mg/kg suspension); duration 9 consecutive months, once daily oral gavage; 2 dogs/sex at 50 mg/kg had a 1-month recovery; animals 4 male/4 female per group (control, 1, 6, 50 mg/kg) plus 2 male/2 female recovery group.
1 (Control) 0 mg/kg /0.5% methylcellulose 4 male/4 female 2 1 mg/kg (0.12X - 0.25X) 4 male/4 female 3 6 mg/kg (0.72X - 1.48X) 4 male/4 female 4a 50 mg/kg (4.88X - 10.16X) 4 male/4 female 4b 50 mg/kg with 1 month recovery (4.88X - 10.16X) 2 male/2 female
| Finding | Quote |
|---|---|
| GI events (vomiting; loose, bloody and/or mucous stools) in all groups, higher incidence in grapiprant-treated dogs | Adverse gastrointestinal (GI) events of vomiting, and loose, bloody and/or mucous stools were observed in all groups including control; however, the incidence was higher in dogs administered grapiprant compared with that in control animals. |
| Decreased mean serum albumin (14%) at 50 mg/kg and decreased A/G ratio (16%) at 6 mg/kg; reversible | Clinical chemistry evaluations showed a significant decrease in mean serum albumin at Weeks 26 and 39 (14% decrease in grapiprant-treated vs control value) at the 50 mg/kg dose (4.88X – 10.16X) and in mean A/G ratio at Week 39 (decrease of 16%) at the 6 mg/kg dose (0.72X – 1.48X). |
| Mild regeneration of ileal mucosal epithelium in one 50 mg/kg dog | One dog in the 50 mg/kg group (4.88X – 10.16X) had mild regeneration of the mucosal epithelium of the ileum. |
| Minimal-mild muscular esophageal degeneration/necrosis in three 6 mg/kg dogs | Three dogs in the 6 mg/kg group (0.72X – 1.48X) had minimal-mild muscular esophageal degeneration/necrosis. |
| Conclusion: up to 50 mg/kg for 9 months associated with mild GI signs; vomiting and reversible decreases in total protein/albumin dose-related | Grapiprant at doses up to 50 mg/kg (4.88X - 10.16X dose level of tablets) for 9 months was associated with mild gastrointestinal signs such as soft or watery stools with mucus and/or blood. Vomiting and mild, reversible decreases in total protein and albumin were also associated with grapiprant, with the incidence increasing with increased doses. |
Effectiveness
Multi-center (16 US sites), placebo-controlled, randomized, masked field study (Study AT001-CCL-14-005); GALLIPRANT 2 mg/kg orally once daily for 28 days vs vehicle control, 1:1; 285 client-owned dogs with OA enrolled; n = 262 in per-protocol effectiveness population; primary endpoint: Percent treatment success at Day 28 by owner CBPI (Pain Severity Score reduced by >= 1, Pain Interference Score reduced by >= 2, overall impression same or better); result: Success rate 48.1% GALLIPRANT vs 31.3% control, p = 0.0315
In the 262 dogs evaluated for effectiveness a statistically significant difference (p = 0.0315) was demonstrated between the success rate in the GALLIPRANT tablet group (48.1%) when compared to the control group (31.3%).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting | 24/141 | 9/144 | N = 141 Vehicle control (tablets minus grapiprant) N = 144 Vomiting 24 9 Diarrhea, soft stool 17 13 Anorexia, inappetence 9 7 Lethargy 6 2 Buccal ulcer 1 0 Immune mediated hemolytic anemia 1 0 |
| Diarrhea, soft stool | 17/141 | 13/144 | N = 141 Vehicle control (tablets minus grapiprant) N = 144 Vomiting 24 9 Diarrhea, soft stool 17 13 Anorexia, inappetence 9 7 Lethargy 6 2 Buccal ulcer 1 0 Immune mediated hemolytic anemia 1 0 |
| Anorexia, inappetence | 9/141 | 7/144 | N = 141 Vehicle control (tablets minus grapiprant) N = 144 Vomiting 24 9 Diarrhea, soft stool 17 13 Anorexia, inappetence 9 7 Lethargy 6 2 Buccal ulcer 1 0 Immune mediated hemolytic anemia 1 0 |
| Lethargy | 6/141 | 2/144 | N = 141 Vehicle control (tablets minus grapiprant) N = 144 Vomiting 24 9 Diarrhea, soft stool 17 13 Anorexia, inappetence 9 7 Lethargy 6 2 Buccal ulcer 1 0 Immune mediated hemolytic anemia 1 0 |
| Buccal ulcer | 1/141 | 0/144 | N = 141 Vehicle control (tablets minus grapiprant) N = 144 Vomiting 24 9 Diarrhea, soft stool 17 13 Anorexia, inappetence 9 7 Lethargy 6 2 Buccal ulcer 1 0 Immune mediated hemolytic anemia 1 0 |
| Immune mediated hemolytic anemia | 1/141 | 0/144 | N = 141 Vehicle control (tablets minus grapiprant) N = 144 Vomiting 24 9 Diarrhea, soft stool 17 13 Anorexia, inappetence 9 7 Lethargy 6 2 Buccal ulcer 1 0 Immune mediated hemolytic anemia 1 0 |
Extraction notes: TAS design_quote is the dosing-group table (Table 6) because it is the only contiguous span giving group sizes; the 9-month study used a methylcellulose suspension, and dose multiples (X) are exposure-bridged to the tablet relative to a 3 mg/kg maximum dose-band dose (fed-fasted range). PK values are from the bridging study (tablet vs suspension); no absolute bioavailability or half-life values are given in the summary. Adverse reactions from Table 5 of the pivotal field study (GALLIPRANT N=141, control N=144).
Reproduce: foi_structured_search(query="Grapiprant") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).