Wyeth MNTX
Methylnaltrexone
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of MOA-728 in the Treatment of Opioid Induced Constipation in Patients with Non-Malignant Pain

Sponsor: Wyeth
Study Drug: Methylnaltrexone (MNTX) MOA-728 @ 10, 50, 150, 400, 600 mgm vs Placebo
Protocol: 3200A3-200-WW
Phase 2
CRO:
CRA: Site #:
Investigator #:
CRA: Fiona Markwood 202-237-6664/Fax: 202-237-6664
Central Lab:
IRB:
Subjects 960 / 120 Sites: 8 Subjects per Site
RM = Rescue Medication: Dulcolax (Bisacodyl): Pts who do not have a BM for > 3 consecutive days during either the screening or treatment period may utilize a rescue dose of oral Dulcolax up to 2 times per week.
Length of Study: 7 Weeks
Phase of Study: 2
CSBM: Complete Spontaneous Bowel Movement: A BM that is not stimulated by a rescue medicine and is accompanied by the sensation of complete evacuation

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Wyeth MNTX
Methylnaltrexone

IC
equal/greater than 18
equal/greater than 2 month h/o non-malignant pain due to OA, Back Pain, or Neuropathic Pain with Med. Rec. evidence of the non-malignant condition (non-acute vertebral fractures, OA, etc…) underlying the chronic pain
ECOG Performance Status: 0 or 1
Stable pain and medical status equal/greater than 1 month and expected to remain so for the duration of the study
Already taking MS equal/greater than 20 mgm at a stable dose for at least 2 wks prior to the screening visit
Constipated, as defined by < 3 spontaneous BM’s per wk on average Plus one or more of the following (based on hx of the past month):
a) At least 25% of stools are hard or very hard (Bristol Type 1 or 2)
b) Sensation of incomplete evacuation following a least 25% of BM’s
c) Straining on a least 25% of defecations
Pain is under good control as defined by an NRS (Numerical Rating Scale) of equal/less than 4 on a 0-10 scale
EC
IBD
Fecal Impaction
Adhesions
Megacolon
h/o GI track surgery likely to affect absorption or disposition of an orally administered drug
Guiac Pos stool in the absence of hemorrhoids or fissures
Current Dx of CA
h/o chronic constipation not associated with Opioid therapy
Any h/o ETOH or Drug Abuse
HIV
Hepatitis C
Active Hepatitis B
WC or any Litigation related to an underlying medical condition
Syncope or Orthostatic Hypotension

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Wyeth MNTX
Methylnaltrexone

V1 D -14 Lab, Begin single blind placebo, ICF, EKG +/- 3 Days
V2 D -1 Randomize, EKG x 3 Eight minutes apart
V2a D 1 First dose double-blind study drug
V3 D 7 Lab for PK
V4 D 14 Lab for PK
V5 D 28 Lab for PK, EKG x 3 Eight minutes apart, early term
V6 D 35 Follow-up/End of Study

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Wyeth MNTX
Methylnaltrexone
Equianalgesic Dosing
Opioid Interchange of OxyContin 20 – 80 Equivalent

Morphine Sulfate (Avinza, Kadian) — 40-160
Tramadol (Ultram 50 mgm) — 8 Tabs
Hydrocodone (Lortab, Vicodin) — 20-80
Propoxyphene (Darvocet N100) — II-IV Tabs
Codeine (Tylenol # 3) — 160
Levorphanol (Levodromoran) — 5-20
Hydromorphone (Dilaudid) — 10-40
Oxycodone (OxyIR, Oxycontin, Percocet) — 20-80
Methadone — 5-20
Fentanyl (Duragesic Patch) — 25-100