Selegiline Hydrochloride: what the FDA reviewed for dog products

Anipryl® NADA 141-080, Supplemental approval, December 10, 1998; sponsor Zoetis Inc.; species: Dogs; foi_id 614; FDA PDF

Indication

Control of clinical signs associated with canine Cognitive Dysfunction Syndrome (CDS) (supplemental second claim)

Dose regimen

0.5-1.0 mg/kg, oral, once daily, preferably in the morning, Initially dose to the nearest whole tablet; adjust based on response and tolerance to the drug

This supplement changes the original approval by adding a second claim for use in cognitive dysfunction syndrome at a new dose of 0.5-1.0 mg/kg.

Effectiveness

CD/HT: Phase 1 placebo-controlled, multi-site, dose-range field trial (placebo n=67, 0.2 mg/kg n=65, 1.0 mg/kg n=67 once daily for 4 weeks) followed by Phase 2 open-label 1.0 mg/kg for 8 additional weeks; 199 client-owned aged dogs with acquired cognitive dysfunction enrolled. Supported by CD3 open-label 0.5 mg/kg dose-confirmation trial (73 dogs).; n = 181; primary endpoint: Owner-assessed improvement (telephone interview with behavioral consultants) at week 4 in orientation, activity, sleep pattern, housetraining, responsiveness and greeting behavior; result: At week 4, 1.0 mg/kg improved sleep pattern (52.7% vs 16.7% placebo, p=0.001), activity (54.7% vs 28.6%, p=0.012) and housetraining (p=0.030); trends indicate 1.0 mg/kg more effective than 0.2 mg/kg; duration of effect may be as short as 8 weeks in about 50% of cases

Results of the 4-week study are based on 181 evaluable dogs.

Adverse reactions

Extraction notes: Supplemental approval: no new target animal safety study (safety refers to the May 30, 1997 original FOI), so target_animal_safety is null. Table 4 pooled AEs from CD/HT and CD3: placebo n=67 (Phase 1 of CD/HT), Anipryl n=272. The extracted text splits 'Syndrome' as 'Syndrom e' in the indication sentence and renders the ® after 'Anipryl' as a private-use glyph; quotes were chosen to avoid the glyph and copy the split as extracted.

Anipryl® NADA 141-080, Original approval, May 30, 1997; sponsor Zoetis Inc.; species: Dogs; foi_id 2554; FDA PDF

Indication

Control of clinical signs associated with uncomplicated canine pituitary dependent hyperadrenocorticism (PDH)

Dose regimen

1 mg/kg (0.45 mg/lb) initial; may be increased to a maximum of 2 mg/kg, oral, once daily, in the morning, Re-evaluate regularly during the first two months; increase to 2 mg/kg only if no improvement after 2 months of therapy

After confirmation of the diagnosis of PDH, Anipryl is recommended orally once daily at an initial dose of 1 mg/kg (0.45 mg/lb) body weight, administered in the morning. During the first two months of therapy, the patient should be re-evaluated regularly for clinical response by history and physical examination. If no improvement in clinical signs or physical examination findings is evident after 2 months of therapy, the dose can be increased to a maximum of 2 mg/kg once daily.

Target-animal safety

dose multiples 0.5X (1 mg/kg/day), 1X (2 mg/kg/day), 1.5X (3 mg/kg/day), 3X (6 mg/kg/day); duration 183 consecutive days (6 months), oral, placebo-controlled; animals 40.

Purpose: to determine the safety of Anipryl® when administered, per os, at 0.5, 1, 1.5 and 3 times the maximum daily level to adult dogs over a period of 6 months, as compared to a placebo control. Animals : 40 beagle dogs (20 male and 20 female) were assigned to one of five treatment groups with each group containing 4 males and 4 females.

Effectiveness

PDH3: open-label, multi-site clinical field trial, dogs served as their own controls; Anipryl 1 mg/kg orally once daily for 6 months in client-owned dogs with confirmed PDH (pivotal for the 1 mg/kg dose). Supported by PDH2 open-label dose-range trial (0.5/1.0/2.0 mg/kg, 41 dogs) and PDH4 open-label 2 mg/kg trial (39 dogs).; n = 52; primary endpoint: Investigator monthly clinical assessment (slightly improved/improved vs same/worse) and owner-reported quality of life; LDDS test results as endocrine measure; result: 34/52 (65%) slightly improved or improved at month 1 and 88% by month 2; final assessment 43/52 (83%) improved; 21% failure rate; population LDDS results improved significantly but did not correlate with individual clinical response

As summarized in the following table, during the first month of therapy, 34 of 52 dogs (65%) were assessed as either slightly improved or improved and 88% were either slightly improved or improved by month 2.

Adverse reactions

Extraction notes: Adverse-event table pooled from the three open-label field trials (PDH2/PDH3/PDH4, N=132, no placebo control) was flattened by PDF extraction (counts run into terms, e.g. 'vomiting20diarrhea18'); counts were read from that flattened row, quoted as extracted. No pharmacokinetic data in this summary. Effectiveness block is the PDH3 (1 mg/kg) trial; PDH4 (2 mg/kg, 39 dogs) reported 54%/61% response at months 1/2.