3 October 2006
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Hip & Knee Pain
ALO-KNT-302

A Long-Term, Open-Label, Safety Study in Subjects with Moderate to Severe Nonmalignant Pain

Sponsor: inc Research
Study Drug: Kadian NT
Protocol: ALO-KNT-302
Phase 3
CRO: Alpharma
Site #:
CRA:
Central Lab: ICON
IRB: Copernicus
Subjects 420/ Sites -> Subjects per Site R 1:1 to:

3 October 2006
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Hip & Knee Pain
ALO-KNT-302

IC
Age 18-70
OA Hip or Knee moderate to severe

EC
BMI > 45
Beck Depression Score equal/more than 18
Hepatitis B or C
Injury target joint within 12 weeks
Sciatica
Workman’s Comp or Litigation
Any new adjunctive OA therapy such as PT within 1 month Screening Visit

3 October 2006
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Hip & Knee Pain
ALO-KNT-301

V1 W Scr. Lab, ICF, Screening, EKG, Washout, RM OK, Hold RM 48H prior to V2
V2 W Baseline Lab, Baseline, If meet Flare Criteria, R to: Vicodin CR vs. Placebo. Begin Titration-Up Period:
. take 1 Tab Vicodin® CR 15/500 HS vs. Placebo x 4days, then ? 1 Tab BID x 3 days (Baseline-Titration)
. V3 W 1 BT One Tab BID x 1 week (Baseline-Titration)
V4 W 2 BT AM: One Tab + PM: 2 Tabs(Baseline-Titration)
V5 W 3 BT 2 Tabs BID (Baseline-Titration)
V6 W 1M Lab Maintenance Period
V7 W 2M Maintenance Period
V8 W 4M Lab, Maintenance Period
V9 W 6M Lab, Maintenance Period
V10 W 8M Lab
V11 W 12M Lab, EKG
V12 W 13Taper One Tab BID x 4 D -> One Tab Daily x 3 D
V13 W 14 F/U

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Hip & Knee Pain
ALO-KNT-301
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

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Hip & Knee Pain
ALO-KNT-301
Questions

  1. Will there be a grading system to judge the severity of the OA like we used on the BUP trials? Yes -> Pi to assign grade
  2. Will they need an x-ray to prove the have OA of the HIP or KNEE? Yes
  3. We can all do a study like this, but the drop out rate is bound to be high. I hope Abbott appreciates this and is appropriately factored into the budget as it is obvious that there will be many subjects that will withdraw consent due to their pain not being adequately controlled. That is, by definition a potential subject entering this trial would not be adequately controlled with the RM provided. At the investigator meeting in Chicago 23-25 Sept. we should encourage sites to tell subjects that we understand that a third of them will receive placebo with inadequate RM back up and that we expect them to drop out for uncontrolled pain.
  4. Since we are devising a study where up front we are grossly under treating subjects who are in chronic pain, we are to expect compliant subjects to markedly reduce their activity as the only way to diminish the OA pain. Are we planning on compensating subjects higher than usual for requesting them in the name of science to place themselves in harms way in such a fashion? And, this will be needed to be spelled out in the ICF regarding how the study plans to restrict pain medication to a group of patients that are accustomed to taking them more often and in stronger forms than they will be provided in the study and that we expect them to withdraw consent if the pain becomes too severe or their disability worsens.
  5. Will there be a disability questioner like the BUP to capture how the OA is impacting their QOL and what they can or can not due with their pain? No