Oral methylnaltrexone does not negatively impact analgesia in patients with opioid-induced constipation and chronic noncancer pain

Figures & data

Table 1 Patient demographic and baseline characteristics

Characteristic	Oral methylnaltrexone			Placebo (n=201)
	150 mg (n=201)	300 mg (n=201)	450 mg (n=200)
Mean age, years (SD)	50.9 (10.3)	51.5 (10.5)	51.4 (10.5)	52.6 (10.3)
Sex, n (%)
Female	133 (66.2)	114 (56.7)	128 (64.0)	130 (64.7)
Male	68 (33.8)	87 (43.3)	72 (36.0)	71 (35.3)
Race, n (%)
White	164 (81.6)	158 (78.6)	172 (86.0)	166 (82.6)
Black/African American	30 (14.9)	38 (18.9)	25 (12.5)	27 (13.4)
Other	7 (3.5)	5 (2.5)	3 (1.5)	8 (4.0)
Primary pain condition, n (%)
Back pain	132 (65.7)	136 (67.7)	135 (67.5)	145 (72.1)
Arthritis	20 (10.0)	15 (7.5)	19 (9.5)	12 (6.0)
Neurologic/neuropathic pain	16 (8.0)	13 (6.5)	16 (8.0)	11 (5.5)
Joint/extremity pain	13 (6.5)	16 (8.0)	11 (5.5)	10 (5.0)
Fibromyalgia	15 (7.5)	8 (4.0)	11 (5.5)	12 (6.0)
Other	5 (2.5)	13 (6.5)	8 (4.0)	11 (5.5)
Baseline MED, mg/daya	141.1	177.5	155.6	132.0
Median (range)	(30.0–1280.0)	(47.4–2289.3)	(27.0–1272.0)	(42.6–1077.3)
Mean (SD)	200.0 (205.2)	252.6 (298.1)	218.0 (189.1)	209.7 (199.1)
Mean pain intensity score (SD)	6.4 (1.8)	6.4 (1.9)	6.4 (1.9)	6.2 (2.1)

Notes:

a Baseline opioid dose defined as average of daily oral MED during screening (within 30 days of first dose of study drug): calculated as (sum of total oral morphine equivalents during screening)/(number of days during screening).

Abbreviation: MED, morphine equivalent dose.

Table 2 Changes in pain intensity during treatment with oral methylnaltrexone

Characteristics	Oral methylnaltrexone			Placebo (n=201)
	150 mg (n=201)	300 mg (n=201)	450 mg (n=200)
Day 14
Mean score (SD)	6.3 (1.9)	6.2 (2.1)	6.4 (1.9)	6.1 (2.0)
Mean change from baseline	−0.1	−0.1	0.0	−0.1
Change vs placeboa (95% CI)	0.0 (−0.3, 0.3)	0.0 (−0.3, 0.4)	0.2 (−0.2, 0.5)
P-value	0.9	0.8	0.3
Day 28
Mean score (SD)	6.4 (1.8)	6.5 (2.0)	6.3 (1.9)	6.1 (2.0)
Mean change from baseline	0.1	0.1	0	–0.1
Change vs placeboa (95% CI)	0.2 (−0.1, 0.5)	0.3 (−0.1, 0.6)	0.1 (−0.2, 0.4)
P-value	0.2	0.1	0.5
Day 42
Mean score (SD)	6.4 (1.9)	6.3 (2.0)	6.4 (1.9)	6.2 (2.0)
Mean change from baseline	0	−0.1	−0.1	−0.1
Change vs placeboa (95% CI)	0.1 (−0.3, 0.5)	0 (–0.3, 0.4)	0 (−0.3, 0.4)
P-value	0.6	>0.9	0.9
Day 56
Mean score (SD)	6.4 (1.9)	6.5 (1.9)	6.4 (2.0)	6.3 (1.9)
Mean change from baseline	0	0.1	0	0
Change vs placeboa (95% CI)	0 (−0.3, 0.4)	0.2 (−0.2, 0.5)	0 (−0.4, 0.4)
P-value	0.8	0.4	>0.9
Day 84
Mean score (SD)	6.3 (1.9)	6.5 (1.9)	6.3 (2.0)	6.2 (2.0)
Mean change from baseline	0	0.1	0	−0.1
Change vs placeboa (95% CI)	0.1 (−0.3, 0.5)	0.2 (−0.1, 0.6)	0.1 (−0.3, 0.4)
P-value	0.6	0.2	0.7

Notes:

a Value reflects least-squares mean difference vs placebo.

Figure 1 Median daily morphine equivalent dose over time.

Abbreviation: MED, morphine equivalent dose.

Figure 2 Mean Objective Opioid Withdrawal Scale score^a over time.

Notes: ^aScoring excluded items related to abdominal cramping. ^#P<0.05 vs placebo for change from baseline.
Abbreviation: OOWS, objective opioid withdrawal scale.