21 April 2006
VERSION: 1 2 3 4 5 6 7 8 9

Hip & Knee Pain
A Multicenter, Double-Blind, Placebo-Controlled, Phase III, Efficacy & Safety Study of PTI-821 in Patients 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: M04-697
Phase 3
CRO: SCIREX Corporation
Site #: 313
CRA: Cynthia L. Wiggins, BS, CCRA Wiggins.CynthiaL@Kendle.com
Central Lab: ICON
IRB: Chesapeake
Subjects 400/ 90 Sites -> 12 Subjects per Site R 1:1 to: Vicodin® CR 15/500 2 Tabs BID: Placebo
Medical Monitor: Lauren Moran, MD LMoran@PainTrials.com
Study Manager: Debra Gilmore, RN DGilmore@PainTrials.com

IC
21-75
OA Hip or Knee
Taken an Analgesic for Arthritis Pain for the majority of days in the previous 3 months and for at least 4 days/wk during the previous 4 wks
Must Meet at Least 1 of the Following:
1. Is unable to consistently control index joint pain with Non-Opioid Analgesics or Ultram (Tramadol)
2. Is unable to treat index joint pain with non-opioid analgesics because treatment is medically contraindicated due to side effects or physician judgment
3. Currently requiring an Opioid (single or combination product) for treatment of index joint pain with the equivalent of equal/less than 60 MS inclusive of breakthrough pain medication
Meets the following Flare Criteria at Baseline Visit:
1. Subjects Assessment of Arthritis Pain Intensity by VAS of equal/greater than 40 mm
2. An increase of equal/greater than 10 mm from the Subject's Assessment of Arthritis Pain Intensity by VAS obtained at the Screening Visit
3. Subject’s Global Assessment of Arthritis Status at Baseline Visit if Fair, Poor or Very Poor

EC
Has incurred an injury to the index joint within 3 months prior to Screening Visit
Major Surgery to the index joint within the last year
Joint replacement/reconstruction to the index joint
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

21 April 2006
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Hip & Knee Pain

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
VERSION: 1 2 3 4 5 6 7 8 9

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