16 June 2006
VERSION: 1 2 3 4 5 6 7 8 9

Hip & Knee Pain & LBP
A Long-Term, Open-Label, Safety Study of PTI-821 in Patients with Moderate to Severe Chronic Low Back Pain or with Moderate to Severe chronic Pain Due to Osteoarthritis of the Hip or Knee

Sponsor: Pain Therapeutics, Inc (PTI)
Study Drug: PTI-821 which is a novel controlled-release, abuse-deterrent formulation of Oxycodone.
This novel form of Oxycontin will be used BID & has proprietary technology that will make it more difficult to defeat than classic Oxycontin
Protocol: PTI-821-CM
Phase 3
CRO: SCIREX Corporation
Site #:
CRA:
Central Lab:
IRB:
Subjects 800 / Sites -> Subjects per Site
All subjects to receive PTI-821 (Oxycodone) Bid @ 5, 10, 15, 20, 30, 40, 60, and up to 80 mgm Bid (Total Daily dose 160/Day)
Available pill strengths include: 5, 10, 15, 20, 30, 40 mgm
Medical Monitor: Lauren Moran, MD LMoran@PainTrials.com
Study Manager: Debra Gilmore, RN DGilmore@PainTrials.com

IC
Age equal/greater than 18 and equal/less than 75
OA Hip or Knee x 3 months or LBP x 6 months that is Moderate to Severe in intensity
Taken an Analgesic for Osteoarthritis Pain for the majority of days and for at least 4 days/wk during the previous 4 wks to include:
NSAIDs; Ultram; or Opioid
Must refrain from all other opioids but alright to take other classes of pain meds

EC
On Oxycodone equivalent > 160 mgm per day; Has incurred an injury to the index joint within 6 months prior to Screening Visit
Major Surgery to the index joint within the last year; Joint replacement/reconstruction to the index joint
Weight > 300 or < 100; Gastric Bypass; Arthroscopic or open surgery to the index joint within the last year
Any surgery within 3 months prior to the Screening Visit
h/o Inflammatory Arthritides such as: RA; Seronegative Spondyloarthropathy; Gout, or Pseudogout
Other Chronic Painful Syndromes such as Paget’s disease or FM; Infectious Arthritis involving the index joint
Any steroids x 1 month; Index joint steroids within 2 months
Viscosupplementation therapy (Synvisc or Hylagan) to the index joint within 4 months
More than 4 ETOH Alcoholic Drinks per Day; Cancer within 5 years
Hepatitis A, B or C
AST/ALT equal/greater than 1.5x ULN
Creatinine > 1.5
Major Depression or any Psych disorder x 2 yrs
Unable to discontinue all formulations of prior analgesics (opioid and/or non-opioid) during the Washout Period of the study
Workman’s Comp or Litigation
Any new adjunctive OA therapy such as PT within 1 month Screening Visit

16 June 2006
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Hip & Knee Pain & LBP

V1 W 1 Lab, ICF, Baseline, EKG
(Opioid Withdrawal Monitoring Telephone Visits Days 1-5)
V2 W 2 +/- 2 Days
V3 W 4 +/- 2 Days
V4 W 6 +/- 2 Days
V5 W 8 +/- 2 Days
V6 M 3 Lab, EKG
V7 M 4 Lab, EKG
V8 M 5 Lab, EKG
V9 M 6 Lab, EKG
V10 M 7 Lab, EKG
V11 M 8 Lab, EKG
V12 M 9 Lab, EKG
V13 M 10 Lab, EKG
V14 M 11 Lab, EKG
V15 M 12 Lab, EKG
V16 M 13 Conducted 2-3 weeks after the last dose of study medication

21 April 2006
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Hip & Knee Pain Short
Equianalgesic Dosing
Opioid Interchange of MS 60 mgm Equivalent

Morphine Sulfate (Avinza, Kadian) - 60
Tramadol (Ultram) - 600
Hydrocodone (Lortab, Vicodin - 30
Propoxyphene (Darvocet) - 400
Codeine (Tylenol # 3) - 240
Levorphanol (Levodromoran) - 7.5
Hydromorphone (Dilaudid) - 15
Oxycodone (OxyIR, Oxycontin, Percocet) - 30 Methadone - 7.5
Fentanyl (Duragesic Patch) - 25