DSI: Joseph Saponaro

ATTACH-BUP3015

A Multicenter, Randomized, Double-Blind, Active Comparator Study to Determine the Efficacy and Safety of Buprenorphine Transdermal System (BTDS) 20 or OxyIR® versus BTDS 5 in Subjects with Moderate to Severe Low Back Pain

Sponsor: Purdue Pharma L.P. (PPLP)
Study Drug: Buprenorphine = Subutex = Temgesic = Buprenex BTDS = Buprenorphine Transdermal System: 5, 10 & 20
marketed as an injectable since 1982, BTDS & SL now available in England, over 3100 subjects enrolled
Medical Monitor: Deborah Steiner, MD 203-588-7413/ cell: 203-273-6386/Fax: 203-588-6205 Deborah.Steiner@Pharma.com
CRA: Patricia.Williams@Pharma.com Cell: 910-367-2198
Mu-opioid agonist-related AEs: nausea, vomiting, dizziness, dry mouth, somnolence and constipation
Rescue Drug: ibuprofen 200 or Tylenol if intolerant to ibuprofen
Central IRB: Coast
Central Lab: LabCorp
Site #: 114A
Investigator #: 2384
First Patient: 64001
Alliance Call Center
Phase 3
723 Subjects/60 Sites = 12 Subjects per Site (241 Subjects R in each of the three groups: BTDS 5, BTDS 20 or OxyIR® 10 q h)

IC
Age: 18 years & older
Clinical Dx LBP x 3 months confirmed by X-Ray
Currently on MS 30-80 mgm per day at least 4 days a week for the last month

EC
Other chronic painful conditions frequently requiring analgesic therapy
Unstable Steroids less than 6 weeks
Intra-articular steroid x 6 wks or Hylagan or Synvisc
Workman's compensation or other litigation

The Extension Phase 24 wk (6 month) open-label extension using BTDS 5, 10 and 20 to evaluate the long-term safety and tolerability of BTDS.
72 h later may increase BTDS 10 Patch
72 h after that increase BTDS 20 Patch
OK to use short acting opioids for breakthrough pain

V 1 W -5 Lab, ICF Pre-Randomization /Screen/Prospective Assessment, EKG x 2 10 min. apart, x-ray within 2 yrs, RTC 7d
V 2 W -4 Reduce pain-meds/opioid taper, RTC 7d or sooner if pain (Not longer than 7 d), SOWS Phone call 3 days later, if pain score ? 5 on two consecutive days, may stop taper
V 3 W -3 Poor pain control x 2 d (pain score ? 5 & SOWS ? 23), begin open-label run-in with BTDS 10, opioid taper completed, - EKG x 2 10 min. apart, RTC 7d, reduced non-opioid analgesic to ½ (Advil no more than QID) Phone call 3 days later and increase to 20 if well tolerated. May wait 7 days to increase or flunk out
V 4 W -2 Flunk out if not tolerating BTDS 20 & complete V5 early term., RTC 7d, must use supplemental analgesic medication Apply new BTDS 20 Patch, tell subjects not to take supplemental pain Meds for 48 H prior to V5
V 4.1 W -1 EKG x 4
V 5 D 0 Lab, R if: achieved stable analgesia ? 4 wearing BTDS 20 x 7 days, early term run-in period
V 6 W 1 Call subject 72h prior & tell don't take supplemental analgesic for 48 hrs prior to V
V 7 W 2 Call subject 72h prior & tell don't take supplemental analgesic for 48 hrs prior to V
V 8 W 4 Call, EKG x 4 ten min. apart from each other, Dispense Only 2 wks
V 8.1 W 6 Dispense 2 weeks (No need to see Doctor)
V 9 W 8 Call subject 72h prior & tell don't take supplemental analgesic for 48 hrs prior to V
V 9.1 W 10 Dispense 2 weeks (No need to see Doctor)
V10 W 12 Lab EKG x 4 ten min. apart., Call, Extension Phase BTDS 5 Patch
V11 W 13 (Ext wk 1) 1st Extension Visit, may titrate BTDS up q 72h
V12 W 16 (Ext wk 4)
V13 W 20 (Ext wk 8)
V14 W 24 (Ext wk 12)
V15 W 28 (Ext wk 16)
V16 W 32 (Ext wk 20)
V17 W 36 (Ext wk 24) Lab
V18 W 40 (Ext wk 28)
V19 W 44 (Ext wk 32)
V20 W 48 (Ext wk 36)
V21 W 52 (Ext wk 40)
V22 W 56 (Ext wk 44)
V23 W 60 (Ext wk 48)
V24 W 64 (Ext wk 52) End Study

Equianalgesic Dosing
Opioid Interchange MS 30 – 80 mgm

Morphine Sulfate (Avinza, Kadian) 30-80
Hydrocodone (Lortab, Vicodin) 15-40
Propoxyphene (Darvocet) 225-600
Levorphanol (Levodromoran) 2-5
Hydromorphone (Dilaudid) 4-10
Codeine (Tylenol # 3) 90-250
Oxycodone (OxyIR, Oxycontin, Percocet)15-40
Merperidine (Demerol) 150-400
Methadone 10-27
Tramadol (Ultram) 300-800
Fentanyl (Duragesic Patch) 25-50
Palladone (Hydromorphone XL) 12mgm =Duragesic 50mcg = Oxycontin 40
(Available as: 12, 16, 24, 32)