Progenics MNTX
Methylnaltrexone
A Phase II, double- blind, randomized, dose-cohort escalation study of oral, enteric-coated Methylnaltrexone (MNTX) and placebo in patients with chronic, non-malignant pain and opioid-induced constipation

Sponsor: Progenics Pharmaceuticals, Inc.
Study Drug: Methylnaltrexone (MNTX) @ 75, 150, 300, and 450 mgm vs Placebo in a ratio of: 20:20:20:20:5
Protocol: MNTX 2201
Phase 2
CRO:
Erica Kinsey
Site #:
Investigator #:
CRA:
Central Lab:
IRB:
Subjects 100 / 10 Sites: 10 Subjects per Site
RM = Rescue Medication:
Length of Study: One Year
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
Observational run-in phase: subjects assessed for BM frequency on a strictly controlled laxative regimen for 7-14 days.
Double-Blind treatment phase: 14 Days; R into one of four dose-cohorts in strict sequence from lowest dose of MNTX (75mgm) to highest dose (450mgm). (At least 15 of the planned 25 subjects in a cohort must complete treatment without dose-limiting adverse events before enrollment into the run-in period of the next cohort is permitted. Within each cohort, subjects will be R to receive either MNTX or Placebo in a 4:1 ratio and will receive MNTX or Placebo for 14 days. Sparse PK sampling will be performed in each cohort.)

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Progenics 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 OxyContin equal/greater than 20 mgm but equal/less than 80 mgm per day at a stable dose for at least 2 wks prior to enrollment
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

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Progenics 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