Oral methylnaltrexone is efficacious and well tolerated for the treatment of opioid-induced constipation in patients with chronic noncancer pain receiving concomitant methadone

Figures & data

Table 1 Demographic and baseline characteristics

Parameter	Oral methylnaltrexone			Placebo
	150 mg (n=33)	300 mg (n=30)	450 mg (n=31)	(n=26)
Age, mean, years (range)	47.0 (18–68)	48.1 (24–66)	50.8 (25–71)	47.3 (24–61)
Sex, n (%)
Male	12 (36.4)	17 (56.7)	10 (32.3)	13 (50.0)
Female	21 (63.6)	13 (43.3)	21 (67.7)	13 (50.0)
Race, n (%)
White	29 (87.9)	26 (86.7)	28 (90.3)	25 (96.2)
Black	3 (9.1)	2 (6.7)	3 (9.7)	1 (3.8)
Other	1 (3.0)	2 (6.7)	0	0
Primary pain condition
Back pain	24 (72.7)	20 (66.7)	19 (61.3)	18 (69.2)
Joint/extremity pain	1 (3.0)	3 (10.0)	1 (3.2)	1 (3.8)
Arthritis	2 (6.1)	1 (3.3)	3 (9.7)	4 (15.4)
Neurologic/neuropathic pain	2 (6.1)	2 (6.7)	3 (9.7)	0
Fibromyalgia	3 (9.1)	2 (6.7)	3 (9.7)	1 (3.8)
Other	1 (3.0)	2 (6.7)	2 (6.5)	2 (7.7)
Median baseline MED, mg/day (range)	186.8 (60–1,140)	269.8 (72–2,289)	225.0 (90–720)	170.3 (60–600)
RFBMs per week, mean (SD)	1.5 (1.0)	1.3 (1.0)	1.4 (0.8)	1.3 (1.5)

Abbreviations: MED, morphine-equivalent dose; RFBMs, rescue-free bowel movements.

Figure 1 The number of dosing days resulting in RFBMs increased during the QD phase in patients treated with methylnaltrexone, and those increases were maintained into the PRN phase.

Note: ^aP<0.05 vs placebo.
Abbreviations: PRN, treatment as needed; QD, once daily; RFBMs, rescue-free bowel movements.

Figure 2 Time to achieve RFMB in patients with chronic noncancer pain and OIC receiving methadone was reduced by methylnaltrexone treatment.

Notes: Patients were censored at 24 hours or the time of the second dose. P=0.9 methylnaltrexone 150 mg vs placebo. P=0.02 methylnaltrexone 300 mg vs placebo. P=0.07 methylnaltrexone 450 mg vs placebo.
Abbreviations: OIC, opioid-induced constipation; RFBM, rescue-free bowel movement.

Figure 3 The percentage of patients responding to methylnaltrexone treatment in each treatment arm showed a trend for higher methylnaltrexone doses to increase the odds of responding.

Notes: ^aResponder was defined as a patient who had ≥3 RFBMs/week, with an increase of ≥1 RFBM/week from baseline for at least 3 of the first 4 weeks of the treatment period. P≥0.05 vs placebo for all methylnaltrexone doses.
Abbreviation: RFBM, rescue-free bowel movement.

Table 2 AEsa in patients with chronic noncancer pain and OIC receiving methadone

Patients, n (%)	Oral methylnaltrexone			Placebo
	150 mg (n=33)	300 mg (n=30)	450 mg (n=31)	(n=26)
Any AE	21 (63.6)	21 (70.0)	23 (74.2)	12 (46.2)
Abdominal pain	4 (12.1)	4 (13.3)	10 (32.3)	0
Nausea	2 (6.1)	5 (16.7)	5 (16.1)	0
Diarrhea	1 (3.0)	3 (10.0)	4 (12.9)	0
Flatulence	3 (9.1)	2 (6.7)	1 (3.2)	2 (7.7)
Hyperhidrosis	3 (9.1)	3 (10.0)	1 (3.2)	0
URTI	2 (6.1)	1 (3.3)	0	3 (11.5)
Fall	3 (9.1)	1 (3.3)	0	0
Upper abdominal pain	0	3 (10.0)	0	0

Note:

a Reported in ≥8.0% of patients in any treatment group during QD, PRN, and follow-up periods.

Abbreviations: AE, adverse event; OIC, opioid-induced constipation; PRN, treatment as needed; QD, once daily; URTI, upper respiratory tract infection.