Background: Two phase 3 trials (301 and 302) showed subcutaneous (SC) methylnaltrexone was well tolerated and induced laxation in patients with advanced illness who had opioid-induced constipation (OIC) while maintaining central analgesia. 

Objective: Evaluate improvement in constipation in cancer patients treated with methylnaltrexone in these two trials.

Methods: In Study 301, 124 cancer patients received a single dose of methylnaltrexone (SC 0.15mg/kg, 0.30mg/kg) or placebo. In Study 302, 78 cancer patients received 0.15mg/kg SC QOD methylnaltrexone or placebo for 2 weeks. Patients had advanced illness and life expectancy of ≥1-6 months.  Patients had OIC with no laxation within 48 hours and/or <3 laxations during the preceding week and were maintained on stable opioids and baseline laxatives.  Primary efficacy endpoints: rescue-free laxation within 4 hours after a single or first dose of study drug; rescue-free laxation within 4 hours for ≥2 of the first 4 doses (Study 302). 

Results: Over half of methylnaltrexone-treated cancer patients had laxation within the first 4 hours of study drug administration (Table).  No clinically significant changes in pain scores or evidence of central opioid withdrawal were observed.

Time to values	Placebo	Methylnaltrexone 0.15 mg/kg	p-Value	Methylnaltrexone 0.30 mg/kg	p-Value
Study 301 – Patients, n	42	37		45
Rescue-free laxation within 4 hours, n (%)	7 (16.7)	22 (59.5)	0.0001**	25 (55.6)	0.0003**
Rescue-free laxation within 24 hours, n (%)	12 (28.6)	25 (67.6)	0.0007*	28 (62.2)	0.0025*
Study 302- Patients, n	41	37		NA
Rescue-free Laxation within 4 hours, n (%)	6 (14.6)	19 (51.4)	0.0007*
Rescue-free laxation within 4 hours after ≥2 of the first 4 doses, n (%)	3 (7.3)	22 (59.5)	<0.0001*
* Fishers exact test, ** Cochran-Mantel-Haenszel

Conclusions:  Methylnaltrexone significantly induced laxations without affecting analgesia or opioid withdrawal in these cancer patients with advanced illness and OIC.