FREEDOM OF INFORMATION SUMMARY Flipbook PDF

FREEDOM OF INFORMATION SUMMARY . ANIPRYL (selegiline hydrochloride) Tablets . ... Dr. Steve Dullard : Mendota . IL : Dr.

---

198 Views
109 Downloads
FLIP PDF 579.89KB

DOWNLOAD FLIP

REPORT DMCA

Approval Date: December 10, 1998

FREEDOM OF INFORMATION SUMMARY

ANIPRYL (selegiline hydrochloride) Tablets for use in dogs NADA 141-080

Pfizer, Inc. Groton, CT 06340

Freedom of Information Summary Page 2 Freedom of Information Summary ANIPRYL TABLETS Table of Contents Section

Page

1. General Information

1

2. Indications for Use

1

3. Dosage Form, Route of Administration and Recommended Dosage

1

4. Effectiveness

1

5. Safety

12

6. Human Safety

14

7. Agency Conclusions

14

8. Labeling

14

1. General Information: NADA Number:

141-080

Sponsor:

Pfizer, Inc. 812 Springdale Dr. Exton, PA 19341

Generic Name:

selegiline hydrochloride, the levorotatory form of deprenyl HCl

Trade Name:

Anipryl

Marketing Status:

Rx: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Effect of Supplement:

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.

2. Indications for Use: Anipryl tablets are indicated for the control of clinical signs associated with canine Cognitive Dysfunction Syndrome (CDS). 3. Dosage Form, Route of Administration, and Recommended Dosage(s): The recommended dosage for oral administration for the control of clinical signs associated with cognitive dysfunction is 0.5 -1.0 mg/kg once daily, preferably administered in the morning. Initially, dogs should be dosed to the nearest whole tablet. Adjustments should then be made based on response and tolerance to the drug. 4. Effectiveness: CD/HT- Study of Anipryl Effects on Cognitive Dysfunction in Aged Dogs Type of study:

Investigators:

Phase 1 - Placebo controlled, multi-site, dose range clinical field trial Phase 2 - Open label, dose confirmation study

Freedom of Information Summary Page 2 Investigator Name Dr. Kimberly Anderson Dr. Tim Anderson Dr. Joan Antle Dr. Gari-Anne Austin Dr. Richard Austin Dr. Susan Baker Dr. Megan Bamford Dr. Glen Baron Dr. Mildred Bass Dr. Pete Beeman Dr. Lark Behrens Dr. James Bianco Dr. Gwen Bilyk Dr. James Blackert Dr. Julie Bobb Dr. Diana Bochenski Dr. Leanne Brandt Dr. Rosemary Branson Dr. J.M. Brechin Dr. Brian Brock Dr. Barbara Bucki-Ohm Dr. Colin Bullmore Dr. Colleen Calderwood Dr. Karen Campbell Dr. Catherine Cannella Dr. Richard Caputo Dr. Anthony Castrignano Dr. Charles Chase Dr. Ruth Chodrow Dr. Philip Coccari Dr. Lori Coles Dr. Kimberly Collett Dr. Bruce Coston Dr. Colleen Coyne Dr. Brad Craig, Jr. Dr. Gerald Crawley Dr. Julia Cummings Dr. James Cupp Dr. Leighann Daristotle Dr. Paul Davis Dr. Nancy Delaney Investigator Name Dr. Don Dinges Dr. Eva Divita Dr. David Dorn

City Redford Bakersfield Lyndhurst Lawrenceville Kissimmee West Palm Beach Covina Matthews Farragut San Francisco Tucson Ardmore Saint Louis Sugarland Lexington Buellton Salt Lake City Blythewood Destin Marianna West Coxsackie Hamlin Rockville Bellevue Fairfield Dearborn Heights Springfield Cherry Hill Staunton Oakdale Salisbury Alliance Woodstock Des Moines Winston Salem Mukwonago Walnut Creek Kansas City Lewisburg Hanover Fishkill City Leawood Port Richey Pittsburgh

State MI CA OH GA FL FL CA NC TN CA AZ PA MO TX KY CA UT SC FL FL NY PA VA NE CT MI VT NJ VA NY NC NE VA WA NC WI CA MO OH MA NY State KS FL PA

Freedom of Information Summary Page 3 Dr. Coleen Dossey Dr. Paul Drewry Dr. Dennis Dugger Dr. Steve Dullard Dr. Jon Duncan Dr. Carol Eklund Dr. A. Susan Elkins Dr. Peter Farrell Dr. Thomas Favale, Jr. Dr. Susan Ferraro Dr. Jo Fisher Dr. Arnold Fleisher Dr. Molly Foley Dr. Leeann Foster Dr. Joni Freshman Dr. Luke Fry Dr. Patricia Funnell Dr. Orlando Garza, Jr Dr. Alan Gassel Dr. Elizabeth Gatti Dr. Thomas Geiselhardt Dr. Deborah Germeroth Dr. Brian Ghere Dr. Ann Goldhammer Dr. Norman Goldstein Dr. Patricia Grant Dr. Jonathan Grant Dr. Marthina Greer Dr. Rick Grgurich Dr. Thomas Haig Dr. Marc Hardin Dr. Mike Harter Dr. Cathy Hartney Dr. Lisa Hatfield Dr. Kathi Heiber Dr. Nan Henderson Dr. Deirdre Hensen Dr. Chad Higgins Dr. Kathy Hinkle Dr. Leslie Hirsch Investigator Name Dr. Robert Hirt Dr. Christopher Holenstein Dr. Keith House Dr. Kaaren Howe Dr. Eric Hudson

Pleasanton Ludington Oklahoma City Mendota Eugene Boise Hanover Alexandria St. Charles Chicago Bradley Hempstead West Chester Los Alamos Colorado Springs Lenexa Ft. Wayne El Paso Farragut Hadley Englewood Colorado Springs New Orleans Glendale Manlius Marina Shokan Lomira Emmaus Minden Overland Park Rockford Bayfield Phoenix Mahopac Durham Patchogue Cridersville Rohnert Park West Roxbury City East Aurora Gresham Paris Wayzata Brick

CA MI OK IL OR ID PA VA IL IL IL NY PA NM CO KS IN TX TN MA CO CO LA AZ NY CA NY WI PA NV KS IL CO AZ NY NC NY OH CA MA State NY OR TX MN NJ

Freedom of Information Summary Page 4 Dr. Susanne Hughes Dr. Laura Hulsey Dr. Keith Huston Dr. Curtis Ish Dr. C. Gordon Jewett Dr. Robert Johnson Dr. Marcy Keefe Dr. Nancy Kelso Dr. Jay King Dr. Nicki Kominek Dr. Harold Krug Dr. David Kuykendall Dr. David Langford Dr. Melanie Lavergne Dr. Christina Leone Dr. James Lindley Dr. Jean Lindley Dr. Jim Lofgren Dr. Reid Loken Dr. Patricia Luttgen Dr. Candace Major Dr. Chris Mangini Dr. Ken May Dr. K. Sue Mc Dougal Dr. Nancy Mc Gregor Dr. Michael McCreight Dr. Robert McDonald Dr. Lynn McEwan Dr. Chaim Mei-Tal Dr. Dawn Metzger Dr. Kim Michels Dr. Don Miller Dr. John Moffa Dr. Susan Moon Dr. David Moreman Dr. Jack Musgrave Dr. Christine Myers Dr. Vincent Obsitnik Investigator Name Dr. Caroline O'Dair Dr. Pamela Ogden Dr. Garret Okumura Dr. Dale Olm Dr. Jacqueline Ordronneau Dr. Vern Otte, Dr. Cheryl Jones Dr. Dennis Ovitsky

Durham Jackson Mentor Hamburg Spokane Berryton Brookfield Charlottesville O'Fallon Dixon Dallas Birmingham Hollywood La Place Oakwood Tempe Miles City Greensboro Acton Lakewood Dallas Woodstock Melrose Park Pensacola Grove Seminole Starkville Palmdale Northridge Denver Kenner San Antonio Aberdeen Memphis Front Royal New Port Richey Middletown Peachtree City City Rancho Palos Verdes Eau Claire Campbell Benicia Seattle Leawood Pittsfield

NC WY OH NJ WA KS WI VA MO CA TX AL MD LA GA AZ MT NC CA CO TX VT IL FL OK OK MS CA CA CO LA TX MD TN VA FL OH GA State CA WI CA CA WA KS MA

Freedom of Information Summary Page 5 Dr. Gerianne Pandolfi Dr. L. Scott Papas Dr. David Payne Dr. Roger Peduzzi Dr. Doug Peterson Dr. Nancy Peterson Dr. Sarah Pratt Dr. Bridget Quatmann Dr. Richard Reierson Dr. Pamela Richard Dr. Eileen Rowan Dr. Gretchen Rowe Dr. Tracy Royer Dr. Frederick Ruhl Dr. Holly Samko Dr. Robert Schladetzky Dr. Ralph Schoemann Dr. Alice Schottenstein Dr. Alan Schreier Dr. Kate Schulze-Kellman Dr. Bruce Silverman Dr. Jim Smith Dr. Richard Smits Dr. Jeff Solomon Dr. Katy Sommers Dr. Ted Staph Dr. William Stehnach Dr. Bruce Steinfeldt Dr. Suzie Steinhauser Dr. Linda Stevelt Dr. Ira Stone Dr. Kevin Stoothoff Dr. Terri Summers Dr. Richard Thoma Dr. Karen Thomas Dr. Mark Thompson Investigator Name Dr. Teresa Tomchick Dr. David Visser Dr. Dan Walker Dr. Susan Weinstein Dr. Mary Welle Dr. Dennis White Dr. Mary Wictor Dr. Katharine Wilderoter Dr. Jeffrey Williams

Wilmington Canton Santa Paula Hudson Bowling Green Des Moines Sedgwick Roanoke Champlin Prospect Bayville Inver Grove Heights Farmington Oak Creek Greenwood Port Hadlock Guilford Chagrin Falls Pleasantville Tucson West Hollywood Gallway Fort Wayne Terre Haute Ukiah Plano Saint Louis La Belle Gualala North Wood Watertown Ocala Woodbridge Cheektowaga Riverdale Columbia City Issaquah South Bend Dallas Little Rock Urbana Tecumseh Duluth Sarver Jamestown

NC OH CA MA KY IA KS VA MN CT NY MN MO WI IN WA CT OH NY AZ CA NY IN IN CA TX MO FL CA OH CT FL VA NY GA MO State WA IN TX AR IL MI MN PA PA

Freedom of Information Summary Page 6 Dr. Michael Williams Dr. Gail Wolfe Dr. Craig Zabel Dr. Patricia Ziegler

Scottsdale Okemos Sugar Grove Springfield

AZ MI IL MO

Veterinary Behavioral Consultant Investigators: Benjamin L Hart, DVM, ACVB (chief behavioral investigator) Professor of Physiology and Behavior School of Veterinary Medicine University of California at Davis Davis, CA 95616 Kelly D. Cliff, DVM Staff Research Associate School of Veterinary Medicine University of California at Davis Davis, CA 95616 Ilana Reisner, DVM, ACVB Veterinary Behavioral Consultations PO Box 105 Brooktondale, NY 14817 Lisa Darling, DVM Private Consultant Kearney, MO 64060 Heidi Ball, DVM Private Consultant Davis California, 95616 Purpose: 1) To assess the efficacy of Anipryl administered orally once daily for control of clinical signs associated with CDS and 2) To evaluate the clinical safety of Anipryl in dogs. Animals: 199 client-owned dogs (82 males and 117 females) of various breeds with acquired cognitive dysfunction were enrolled. The dogs ranged in age from 7 to 20 years (mean = 13.9 years) and weighed between 4.5 and 152 pounds (mean = 36.7 pounds). Control: During the first 4 week phase, one group received placebo tablets comprised of the formulation excipients without active ingredient The placebo tablets were indistinguishable from Anipryl tablets. Enrollment: Each dog enrolled met the following criteria:

Freedom of Information Summary Page 7 1) Presence of acquired cognitive dysfunction, as documented by the presence of at least 3 of the following cognitive problems: disorientation; decreased activity; increased sleep or changes in sleep/wake cycle; loss of housetraining or reduced signaling behavior (i.e, signals less to go outside); decreased enthusiasm of greeting behavior; decreased responsiveness to attention. 2) Age 10 years or older; giant breed dogs, age 7 years or older. 3) No known concurrent debilitating disease that would preclude monitoring response to therapy. 4) No concurrent treatment or recent treatment with corticosteroids or other medication that could cause polyuria/polydipsia or substantially affect behavior. 5) No concurrent treatment with medications known to interact with Anipryl. Dogs were excluded if they had evidence of concurrent disease or concurrent drug therapy that could preclude monitoring of response to therapy, or if they had other behavioral problems such as aggression. Dosage form: Anipryl formulated into 2 mg, 5 mg, and 15 mg tablets Route of administration: Oral Dosage: 0 mg/kg administered to one group of 67 dogs, 0.2 mg/kg administered to one group of 65 dogs, and 1.0 mg/kg administered to one group of 67 dogs once daily in the morning. Study Duration: Three months, divided into two phases. Phase 1: Three dose groups (placebo, 0.2 mg/kg, or 1.0 mg/kg) were studied for 4 weeks. Phase 2: All dogs were administered 1.0 mg/kg of Anipryl in open label fashion for 8 additional weeks. Variables evaluated: Entrance and post-treatment evaluation criteria consisted of evaluation of the following behaviors: orientation, activity, sleep pattern, housetraining, responsiveness, and greeting behavior. The owner stated if each behavior had worsened, stayed the same, or improved. The owners’ assessments of changes in behavior were obtained by telephone interview with the veterinary behavioral consultants at enrollment, week 4 and week 12. Results: Phase 1-(4-week, placebo controlled dose range study): Results of the 4-week study are based on 181 evaluable dogs. Table 1 shows proportions of dogs that improved following 4 weeks of treatment with Anipryl or placebo. Improvement of individual parameters was evaluated in those dogs with the behavioral abnormality in question at the initiation of the study. Significant improvements were observed in sleep pattern, housetraining and activity. Table 1. Proportion of Improved Dogs at Week 4 by Dose Group

Freedom of Information Summary Page 8 Behavior (Number affected at enrollment) Orientation (179)

Control

0.2 mg/kg

1.0 mg/kg

Overall p-value*

22/62 (35.5%)

24/59 (40.7%)

32/58 (55.2%)

0.098

Activity (166)

16/56 (28.6%)

22/57 (38.6%)

29/53 (54.7%)

0.012

Sleep (164)

9/54 (16.7%)

17/55 (30.9%)

29/55 (52.7%)

0.001

Responsiveness (158)

23/55 (41.8%)

26/55 (47.3%)

25/48 (52.1%)

0.499

Housetraining (157)

15/57 (26.3%)

21/54 (38.9%)

16/46 (34.8%)

0.030

Greeting (145)

12/48 (25.0%)

20/51 (39.2%)

15/46 (32.6%)

0.584

*For the Cochran-Mantel-Haenszel test for nonzero correlation, indicating increased improvement with increasing dose.

Phase 2- (Open label dose confirmation study, continued to week 12): Results of the 8-week open label phase of the study are based on 157 evaluable dogs. Analyses of week 12 evaluations compared the percent improvement at 12 weeks to that observed at 4 weeks of treatment. Table 2 results indicate some dogs that did not improve by week 4 showed improvement by week 12. This tendency to improve was observed in all 3 treatment groups by 12 weeks of treatment regardless of the initial treatment received during the first 4 week period (i.e. placebo, 0.2, or 1.0 mg/kg of Anipryl), indicating that some increased improvement may be seen with extended use, even among high dose (1.0 mg/kg) group animals. Significant improvement occurred in activity, sleep pattern, and housetraining. Table 2. Proportion of Improved Dogs at Week 12 Among Those Not Improved at Week 4 The headings for the proportions below refer to the dosage groups the dogs were in during the first phase of the trial. In phase 2, all dogs received 1.0 mg/kg.

Freedom of Information Summary Page 9 Behavior (n) Orientation (86)

Control 17/35 (48.6%)

0.2 mg/kg 18/29 (62.1%)

1.0 mg/kg 11/22 (50.0%)

Activity (83)

15/35 (42.9%)

15/31 (48.4%)

6/17 (35.3%)

Sleep (96)

12/41 (29.3%)

12/35 (34.3%)

6/20 (30.0%)

Responsiveness (68)

14/27 (51.8%)

12/24 (50.0%)

8/17 (47.1%)

Housetraining (90)

12/36 (33.3%)

18/29 (62.1%)

13/25 (37.1%)

Greeting (82)

7/32 (21.9%)

10/27 (37.0%)

8/23 (34.8%)

To assess the duration of effect, the change between week 4 and week 12 among those dogs who were evaluated as improved at week 4 was evaluated. The proportion of dogs that regressed at week 12 among those improved at week 4 was fairly consistent across the groups. The duration of effect may be as short as 8 weeks in about 50% of the cases. Conclusions: In this clinical trial, Anipryl administered at 1.0 mg/kg once daily was shown to provide safe and effective control of clinical signs associated with CDS in pet dogs. The onset, duration and magnitude of response varied with individual dogs. Based on the results in Table 1, trends indicate that the higher dose of 1.0 mg/kg is more effective than the lower dose of 0.2 mg/kg. Adverse Reactions: Refer to the Safety section (page 12) for adverse events observed in clinical trials. CD3, Multi-Site Clinical Trial of Anipryl for Canine Cognitive Dysfunction Type of study:

Open label, multi-site dose confirmation clinical trial

Investigators: Investigator Name Dr. W.A. Andrews

City Bonner Springs

State KS

Freedom of Information Summary Page 10 Dr. Ward Brown Dr. Don Dinges Dr. Rusty Erickson, Dr. Todd Goodman Dr. Karen Eyer-Stokes Dr. Wayne Hunthausen, Dr. Annette Frerking Dr. Kevin Lesslie Dr. Scott Lichlyter Dr. Keven McShane, Dr. R. Brenton Smith Dr. Vern Otte, Dr. Cheryl Jones, Dr. Keith Longhofer Dr. Dan Reimer, Dr. Mary Haitt Dr. Brian Rind Dr. Jill Sandler Dr. Tom Shackelford Dr. David Theiss Dr. Steve White, Dr. Scott Mickleson Dr. Jarvis Williams, Dr. Sandi Leonard

Kansas City Leawood Mission Overland Park Westwood

MO KS KS KS KS

Shawnee Brentwood Austin

KS CA TX

Leawood

KS

Sepulveda Great Neck Overland Park Carmel Lee’s Summit Fairway Kansas City

CA NY KS IN MO KS MO

Purpose: The objectives of this clinical trial were to assess the efficacy and safety of Anipryl for CDS in the dog. Animals: 73 client-owned dogs (29 males and 44 females) of various breeds with spontaneously occurring CDS were enrolled. The dogs ranged in age from 7 to 19 years (mean = 15 years) and weighed between 8 and 80 pounds (mean = 31 pounds). Controls: Each animal served as its own control. Diagnosis: Diagnosis of CDS was based on the presence of one or more of the following clinical or behavioral signs: decreased appetite, decreased awareness of surroundings, decreased ability to recognize familiar places, people or other animals, decreased hearing, decreased ability to climb up and down stairs, decreased tolerance to being alone, development of compulsive behavior or repetitive behaviors or habits, circling, tremors or shaking, disorientation, decreased activity level, abnormal sleep wake cycles, loss of house training, decreased or altered responsiveness to family members, and decreased or altered greeting behavior. Dogs were excluded if they had evidence of concurrent disease or concurrent drug therapy that could preclude

Freedom of Information Summary Page 11 monitoring of response to therapy, or if they had other behavioral problems such as aggression. Dosage form: Anipryl formulated into 2 mg, 5 mg, and 15 mg tablets Route of administration: Oral Dosage: One dose group was studied: dogs received 0.5 mg/kg orally once daily throughout the trial. Three dogs had an increase in dose to 1.0 mg/kg because of lack of efficacy and two dogs had the dosage halved due to adverse events (hyperactivity). Study Duration: Three months. Variable evaluated: Changes in the behaviors and clinical signs listed below in Table 3. Results: To determine responses to 0.5 mg/kg once daily Anipryl treatment, individual parameters were evaluated in this trial by methods similar to those used in the CD/HT clinical trial. A complete listing of response to individual parameters is displayed in Table 3. The sleep pattern improvement is consistent with the dose response pattern observed for this variable in the CD/HT study. The improvement rates for housetraining, activity, and orientation exceed that observed in 1.0 mg/kg dose group from the CD/HT study.

Table 3. Proportion Improved at 4 Weeks Parameters in bold are the same parameters evaluated in CD/HT clinical trial. Behavior

Proportion* (%)

Housetraining Activity/attention Orientation/awareness Recognition Tolerance to being alone Circling Sleep/wake Whining/whimpering Alertness Response to commands Recognizing people Memory

19/47 (40.4%) 30/51 (58.8%) 28/47 (59.6%) 15/41 (36.6%) 4/31 (12.9%) 8/20 (40.0%) 13/46 (28.3%) 10/29 (34.5%) 31/55 (56.4%) 12/60 (20.0%) 11/46 (23.9%) 11/50 (22.0%)

Freedom of Information Summary Page 12 Learning ability 3/50 (6.0%) Interact with people 12/42 (28.6%) Interact with other dogs 7/47 (14.9%) *The proportions are the number improved over the number with the problem at the beginning of the study. Conclusions: The results of this clinical trial support the inclusion of 0.5 mg/kg as the lower end of a dosage range. 5. Safety: The safety of Anipryl is based on data in the original approval (refer to the Freedom of Information Summary dated May 30, 1997). The information below describes the adverse events reported in the CDS clinical field trials. In the CD/HT clinical trial, 132 dogs were monitored for adverse events while on Anipryl for up to 12 weeks and 67 dogs were monitored on the drug for up to 8 weeks. In the CD3 trial, 73 dogs were monitored while on Anipryl for up to 12 weeks. The following table lists the adverse reactions reported in the 2 clinical trials. The 67 dogs that received placebo during Phase 1 of the CD/HT trial are included.

Table 4: Adverse events from 2 clinical field trials Adverse Event vomiting diarrhea hyperactive/restless* anorexia neurologic** lethargy urinary tract infection salivation weakness pale gums polyuria/polydipsia pruritis/dermatologic weight loss panting cardiovascular/resp*** diminished hearing

Placebo (n=67) 14 (21%) 7 (10%) 4 (6%) 1 (1%) 1 (1%) 1 (1%) 1 (1%) 3 (4%) 0 (0%) 1 (1%) 1 (1%) 1 (1%) 0 (0%) 1 (1%) 0 (0%) 0 (0%)

Anipryl (n=272) 87 (32%) 55 (20%) 42 (15%) 29 (11%) 26 (10%) 20 (7%) 17 (6%) 15 (6%) 15 (6%) 14 (5%) 13 (5%) 13 (5%) 12 (4%) 10 (4%) 10 (4%) 7 (3%)

Freedom of Information Summary Page 13 *includes hyperactive, irritable, anxious, restless, abnormal repetitive movements **includes ataxia, incoordination, staggering, disorientation, decreased proprioception, seizure ***includes heart murmurs, tachycardia, collapse, dyspnea, pleural effusion, sneezing In the CD/HT trial, 5 dogs had the drug discontinued because of the following adverse events: 1) vomiting and diarrhea, 2) hyperactivity, 3) increase in destructive behavior associated with separation anxiety, 4) anemia, and 5) stiffness and polydipsia. In the CD3 trial, 2 dogs had the dosage halved because they became too active and 5 dogs had the drug discontinued because of the following adverse events: 1) vomiting (in 2 dogs); 2) agitation, 3) stargazing and trembling a few hours after the first tablet was given, and 4) possible drug interaction. After being on the drug for about a week one dog experienced weakness, confusion, incoordination and “seizure-like” activity. The dog was also on metronidazole, prednisone, and trimethoprim sulfa. All drugs were discontinued, and the dog returned to normal. A trend in hematocrit levels was noticed during review of individual case reports. Some dogs experienced a drop in hematocrit during the clinical trials. The decreases seen were usually within the normal range and not accompanied by any clinical signs. One dog had a rapid drop below the normal range accompanied by lethargy and anorexia. The dog recovered after the drug was discontinued. 6. Human Safety: Human Safety Relative to Food Consumption: Data on human safety, pertaining to consumption of drug residues in food, were not required. This drug is to be labeled for use in dogs, which are non-food animals. Human Safety Relative to Possession, Handling and Administration: Labeling contains an adequate caution statement. Labeling states: “Keep out of reach of children.” 7. Agency Conclusions: The data in support of this NADA comply with the requirements of Section 512 of the Act and Section 514.111 of the implementing regulations. The data demonstrate that Anipryl (selegiline hydrochloride, L-deprenyl), when used under labeled conditions of use, is safe and effective. Under section 512(c)(2)(F)(iii) of the FFDCA, this approval for non food producing animals qualifies for THREE years of marketing exclusivity beginning on the date of approval because the application contains substantial evidence of the effectiveness of the drug involved, or studies of animal safety required for the approval of the application conducted or sponsored by the applicant.

Freedom of Information Summary Page 14 The drug is restricted for use by or on the order of a licensed veterinarian because professional expertise is required for the diagnosis of clinical signs associated with cognitive dysfunction syndrome and for the monitoring of adverse events and response to therapy. Patent information: The sponsor holds the following patents: 5,225,446 (expires 8-3110); 5,276,057 (expires 1-4-11); 5,387,615 (expires 2-7-12); 5,565,495 (expires 1015-13); 5,561,163 (expires 10-1-13); 5,151,449 (expires 8-31-10); and 5,192,808 (expires 8-31-10). 8. Labeling (attached): Package Insert Cartons for 2, 5, 10, 15 and 30 mg tablets Blister package foil backing for 2, 5, 10, 15 and 30 mg tablets