In a well-controlled, laboratory margin of safety study in healthy, adult cats (see Target Animal Safety ), after repeat daily oral dosing for six months, a slight to moderate increase in exposure to velagliflozin was observed. In addition, a tendency for a less than dose proportional increase of maximum plasma concentration (C max ) and exposure (AUC) over the tested dose range was noted. Following oral administration of SENVELGO in cats at 1 mg/kg, velagliflozin was rapidly absorbed with a median time to maximum concentration of 0.25 hours. The velagliflozin mean (± standard deviation) C max was 1030 (± 361) ng/mL and the mean AUC 0-last to the last quantifiable plasma concentration was 3295 (± 1098) day*ng/mL. The elimination half-life of velagliflozin was 3.68 (± 0.34) hours. Effectiveness: Two hundred and fifty-two (252) cats diagnosed with diabetes mellitus were enrolled in a 180-day multicenter field study. The cats included various purebred and mixed breed cats ranging in age from 4 to 18 years and in weight from 5.7 to 26.5 lbs (2.6 to 12 kg). Cats were administered SENVELGO at a dose of 0.45 mg/lb (1 mg/kg) orally, once daily, regardless of blood glucose level, beginning on Day 0. Cats were evaluated at Days 2 or 3, and Days 7 and 30 and then monthly. Treatment success was evaluated on Day 30 and was defined as improvement in at least one clinical sign of diabetes mellitus (polyuria, polydipsia, unintended weight loss, polyphagia, or diabetic neuropathy) and improvement in at least one blood glucose variable (blood glucose curve mean or serum fructosamine). Of 198 cats included in the effectiveness-evaluable population: • 175 cats (88.4%) were considered a treatment success on Day 30 (lower bound of the two-sided 90% confidence interval was 84%). • Mean blood glucose decreased from 446.4 mg/dL (single fasted sample) prior to Day 0 to 169.8 mg/dL (blood glucose curve mean) on Day 30 • Mean fructosamine levels decreased from 551.4 μmol/L prior to Day 0 to 332.0 μmol/L on Day 30. • Improvements in the clinical signs of polyuria, polydipsia, body weight, polyphagia, and diabetic neuropathy on Day 30 were observed in 125/177 (71%), 128/176 (73%), 133/167 (80%), 33/80 (41%), and 7/30 cats (23%), respectively. • 157 cats completed the 180-day study Target Animal Safety: In a well-controlled laboratory margin of safety study, SENVELGO was administered orally to fasted, healthy, 8 to 9 month old cats at 0, 1, 3, or 5 mg/kg body weight (corresponding to 1X, 3X or 5X the intended labeled point dose of 1 mg/kg) once daily for 26 weeks (6 months). Control cats (0 mg/kg) received saline at a volume equal to the 5 mg/kg dose. There were eight cats per group (4 females, 4 males). All cats survived the study and there were no SENVELGO-related effects on ophthalmic examinations, indirect systolic blood pressure measurements, and blood coagulation parameters. Hypersalivation and vomiting after dose administration occurred infrequently and was only observed in the groups that received SENVELGO. During physical examinations on Days 14 and 28, there was a drug-related decrease in heart rate (< 140 bpm) in the cats that received SENVELGO compared to the control cats. There were no other drug-related effects on physical examinations. Polydipsia, glucosuria, decreased urine creatinine, and diarrhea were reported more frequently in cats that received SENVELGO than in control cats. Reddish, mucoid feces were observed in three instances in the 1X group cats. One cat in the 5X group had decreased activity, vomiting, and reduced feed consumption for one day, and reddened rectal mucous membranes were observed over the next 5 days. Two cats (3X and 5X groups) were each observed to have a reddened prepuce with white-yellow discharge twice during the study that was not associated with abnormal urinalyses. Food consumption was higher in the cats that received SENVELGO compared to the control cats. The rate of body weight gain was lower in the 5X group cats compared to cats in the control, 1X and 3X groups. There were drug-related increases in reticulocyte count, mean corpuscular hemoglobin, mean corpuscular volume, and Heinz body percentage, and a decrease in mean corpuscular hemoglobin concentration in the cats that received SENVELGO compared to control cats. None of the cats showed any clinical signs of anemia and the number of erythrocytes, hemoglobin, and hematocrit values were normal. There was no effect of SENVELGO on white blood cells and platelets. There were drug-related increases in serum magnesium, albumin, cholesterol, and triglycerides in the cats that received SENVELGO, with some magnesium, serum albumin and triglyceride values above the reference range. There was a drug-related decrease in mean BUN in the cats that received SENVELGO. There were no other treatment-related changes in serum chemistry parameters, including serum glucose and symmetric dimethylarginine (SDMA). A reticular pattern was observed on the surface of the liver of one control, three 1X, four 3X, and three 5X group cats. How Supplied: SENVELGO (velagliflozin oral solution) 15 mg/mL, 30 mL nominal fill volume is supplied in a 45 mL plastic bottle with dosing syringe. NDC 0010-4614-01 Storage Information: SENVELGO can be stored at or below 77°F (25°C) with excursions permitted up to 104°F (40°C). Once the bottle is opened, use the contents within six months. Approved by FDA under NADA # 141-568 Marketed by: Boehringer Ingelheim Animal Health USA Inc. Duluth, GA 30096 SENVELGO® and SENVELGO Logo® are registered trademarks of Boehringer Ingelheim Vetmedica GmbH, used under license. ©2023 Boehringer Ingelheim Animal Health USA Inc. All rights reserved. US-PET-0531-2023 Revised 06/2023
Adverse Reactions
Frequency (N=252) Number (%)
Diarrhea (including loose stool)
132 (52.3%) 111 (44%) 92 (36.5%) 46 (18.3%) 42 (16.7%) 39 (15.5%) 34 (13.5%) 33 (13.1%) 29 (11.5%) 28 (11.1%) 20 (7.9%) 19 (7.5%) 18 (7.1%) 18 (7.1%)
Weight loss*
Vomiting Polyuria Polydipsia
BUN †
Anorexia or hyporexia
Hypersalivation and/or gagging Urine specific gravity > 1.060
Dehydration
Lethargy
Polyphagia
Urinary tract infections/cystitis Diabetic ketoacidosis or euglycemic diabetic ketoacidosis ‡
Hypercalcemia
16 (6.3%) 14 (5.6%) 14 (5.6%) 13 (5.2%) 12 (4.8%) 12 (4.8%) 12 (4.8%) 11 (4.4%) 10 (4.0%) 9 (3.6%) 6 (2.4%) 3 (1.2%)
Ketonuria §
Inappropriate urination Death or euthanasia Elevated AST and/or ALT** Hypertriglyceridemia ††
Hyperphosphatemia
Elevated fPL Pancreatitis
Elevated creatinine Hepatic lipidosis Urinary incontinence
* Approximately 80 cats had weight loss during the first week of treatment, likely due to dehydration and/or caloric wasting from glucosuria. † Most cats had elevations ≤ 1.5X upper limit of normal (ULN). ‡ All but 5 cases occurred within 2 weeks of starting SENVELGO. Twelve of these cats had euglycemic diabetic ketoacidosis. § These cats did not progress to diabetic ketoacidosis and all but one developed ketonuria within a week of starting SENVELGO. The cats discontinued SENVELGO and transitioned to insulin. ** Four of these cats had AST (aspartate aminotransferase) and/or ALT (alanine aminotransferase) > 2X ULN. †† These cats sometimes also had elevated cholesterol. The following adverse reactions were seen in the study with < 1% frequency: elevated creatine kinase (> 3X ULN), hypoglycemia without clinical signs (glucose ≤ 50 mg/dL), anemia, abnormal behavior, bradycardia, and dermatitis. Ketonuria and diabetic ketoacidosis: Thirty-two (32) cats developed ketonuria, diabetic ketoacidosis or euglycemic diabetic ketoacidosis and were removed from the study. Twenty-six (26) of these cats developed ketonuria, diabetic ketoacidosis, or euglycemic diabetic ketoacidosis within the first 7 days of treatment with SENVELGO. Thirteen (13) of these cats developed ketonuria without further progression to diabetic ketoacidosis or euglycemic ketoacidosis and were transitioned to insulin. An additional thirteen (13) cats developed diabetic ketoacidosis or euglycemic ketoacidosis. Nine cats recovered after hospitalization and intensive treatment. Three of the 9 cats had concurrent conditions: hepatopathy (1), hepatic lipidosis (1), and pancreatitis and hepatic lipidosis (1). Four of the 13 cats were euthanized; three because the owners declined treatment and one cat was euthanized after not responding to hospitalization and intensive treatment. Six cats developed ketonuria, diabetic ketoacidosis or euglycemic diabetic ketoacidosis after the first 7 days of treatment. One cat developed ketonuria without progression to diabetic ketoacidosis or euglycemic ketoacidosis after more than 4 months on SENVELGO. Five cats developed diabetic ketoacidosis or euglycemic ketoacidosis. Two cats (one with concurrent pancreatitis and hepatic lipidosis) were treated and recovered. One with concurrent pancreatitis was treated and recovered but died several days later. Two of the five cats were euthanized; one cat was euthanized after poor response to hospitalization and intensive therapy; and one was euthanized due to declining condition unrelated to diabetic ketoacidosis. Thirty-eight enrolled cats had been previously treated with insulin. Of those 38 cats, 12 (32%) developed ketonuria, diabetic ketoacidosis, or euglycemic diabetic ketoacidosis during the first week and were removed from the study. These 12 cats are included in the 26 cases reported above and represent 46% of the cases removed in the first week of treatment due to ketonuria or ketoacidosis. Death and euthanasia: Nineteen cats died (3) or were euthanized (16) during the study, or shortly following removal from the study, with thirteen possibly related to SENVELGO use or declining glycemic control. In addition to 6 of the cases associated with diabetic ketoacidosis described above, euthanasia was associated with the following conditions (number of cats): acute renal failure within a week of starting SENVELGO (1), worsening or emergent urinary incontinence associated with poor glycemic control (2), worsening polyuria/ polydipsia and inappropriate urination (1), progressive signs of diabetes mellitus (1), declining condition and suspected pancreatitis (1), azotemia and lack of effect within a week of starting SENVELGO and possible concurrent hypersomatotropism (1). Contact Information: To report suspected adverse drug events, for technical assistance, or to obtain a copy of the Safety Data Sheet (SDS), contact Boehringer Ingelheim Animal Health at 1-888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae. Information for Cat Owners: Please provide and review the Client Information Sheet with cat owners to ensure they understand the entire contents before SENVELGO is administered. The Client Information Sheet contains important information regarding the use of SENVELGO. Owners should be advised to discontinue SENVELGO and contact a veterinarian immediately if their cat develops anorexia, lethargy, vomiting, diarrhea, or weakness.
Clinical Pharmacology: Mechanism of Action:
Velagliflozin is an inhibitor of sodium-glucose cotransporter 2 (SGLT2), the renal transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, velagliflozin reduces the reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion. Pharmacokinetics: In a laboratory study conducted to determine the prandial state of maximum exposure, systemic exposure for velagliflozin was greater in the fasted state than in the fed state by 170% for the mean maximum observed plasma concentration (C max ), and by 45% for the mean area under the plasma concentration versus time curve (AUC) from dosing (time 0) to the last quantifiable concentration (AUC 0-last ), respectively.
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