TABLE 6.
The number of grade 3 and 4 AEs that were reported by investigators for all naïve single tigilanol tiglate treated dogs in phase 1 and 2. Adverse Events are classified according to VCOG category and subcategory (AE type)
| VCOG AE category | AE type | No. grade 3 AEs | No. grade 4 AEs | Related to TT (Y = Yes, P = Possible, N = No) a | Time of occurrence posttreatment (d) |
|---|---|---|---|---|---|
| Administration site conditions | Pain at Tx site | 2 | 1 | Y | 0 and 5 |
| Wound at Tx site | 3 | Y | 5, 7, and 12 | ||
| Wound infection | 1 | P | 9 | ||
| Scar contracture | 2 | Y | 33 and 47 | ||
| Blood/bone marrow | Leukocytosis and neutrophilia | 2 | Y | 12 and 26 | |
| Thrombocytopenia | 1 | P | 26 | ||
| Cardiac arrhythmia | Sinus tachycardia | 1 | Y | 0 | |
| Constitutional clinical signs | Lethargy/fatigue/general performance | 1 | P | 12 | |
| Dermatologic/skin | Pruritus | 1 | P | 14 | |
| Gastrointestinal | Constipation | 1 | N | 39 | |
| Inappetence | 1 | P | 21 | ||
| Hemorrhage/bleeding | Ingestion of toxic level of NSAID's | 1 | N | 84 | |
| Metabolic/laboratory | ALP elevation | 1 | N | 8 | |
| ALT elevation | 1 | N | 6 | ||
| CPK elevation | 1 | N | 54 | ||
| GGT elevation | 1 | N | 8 | ||
| Triglyceridemia | 1 | N | 8 | ||
| Musculoskeietal/soft tissue | Extremity (gait/ambulation) lameness at Tx site | 5 | 1 | Y | 0, 1, and 9 |
| Neoplasms benign, malignant, etc | Primary pelvic mass b | 1 | N | 33 | |
| Primary bone neoplasia | 1 | N | 53 | ||
| Neurology | Somnolence/depressed/dullness | 1 | P | 0 | |
| Neuropathy: cranial nerve CNVII | 1 | N | — c | ||
| Neuropathy: motor | 1 | P | 8 | ||
| Renal/genitourinary | Proteinuria | 2 | N | 9 or 29 | |
| Obstruction, urinary | 1 | N | 39 | ||
| Vascular | Thrombosis/thrombus/embolism b | 1 | N | 63 |
Abbreviations: AE, adverse event; MCT, mast cell tumor; TT, tigilanol tiglate; VCOG, Veterinary Cooperative Oncology Group.
Investigator opinions of the potential causes of AEs as whether they were related to TT treatment or not. Yes (Y) are the combined VCOG AE Attribution Standards of Definite/Probable, defined as AEs that is clearly or likely to be related to TT treatment; Possible (P) is the VCOG AE Attribution Standard that is defined as an AE that may or may not be related to TT treatment; No (N) are the combined VCOG AE Attribution Standards of Unrelated/Unlikely, these are AEs that are doubtful or not related to TT treatment.
Death due to thrombus was found on post mortem to be attributable to the development of a primary pelvic mass not related to the treated MCT.
Occurred 16 days prior to TT treatment in a control dog treated in phase 2 of the study.