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Fixed-Dose Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: Results of a Randomized, Placebo-Controlled Study and Open-Label Extension.

Bull J, Wellman CV, Israel RJ, Barrett AC, Paterson C, Forbes WP - J Palliat Med (2015)

Bottom Line: Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001).Efficacy results during the OLE study were consistent with the RCT.MNTX demonstrated a favorable safety profile in the RCT and OLE study.

View Article: PubMed Central - PubMed

Affiliation: 1 Four Seasons , Flat Rock, North Carolina.

ABSTRACT

Background: Subcutaneous methylnaltrexone (MNTX), dosed based on body weight, is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); however, fixed-dose administration of MNTX may improve ease of administration.

Objective: The study objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4 trials.

Methods: In a double-blind, randomized, placebo-controlled trial (RCT), patients with advanced illness and OIC received MNTX (8 mg or 12 mg by body weight [38 kg to <62 kg or ≥62 kg, respectively]) or placebo every other day (QOD) for two weeks. Patients completing the RCT could enroll in an open-label extension (OLE) study with MNTX administered as needed (PRN). The primary endpoint was percentage of patients with a rescue-free bowel movement (RFBM) within four hours after ≥2 of the first 4 doses in the first week.

Results: In the RCT, 116 and 114 patients received MNTX and placebo, respectively, and 149 patients continued to the OLE study. The percentage of patients achieving primary endpoint was 62.9% and 9.6% for MNTX and placebo groups, respectively (p<0.0001). Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001). Efficacy results during the OLE study were consistent with the RCT. MNTX demonstrated a favorable safety profile in the RCT and OLE study.

Conclusion: Fixed-dose MNTX administered QOD in the RCT and PRN in the OLE study demonstrated robust efficacy and was well tolerated in treating OIC in patients with advanced illness.

No MeSH data available.


Related in: MedlinePlus

RFBM within four hours after ≥2 of the first 4 doses of MNTX or placebo in the first week of treatment in the RCT. MNTX, methylnaltrexone; RCT, randomized, placebo-controlled trial; RFBM, rescue-free bowel movement.
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Related In: Results  -  Collection


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f2: RFBM within four hours after ≥2 of the first 4 doses of MNTX or placebo in the first week of treatment in the RCT. MNTX, methylnaltrexone; RCT, randomized, placebo-controlled trial; RFBM, rescue-free bowel movement.

Mentions: For the primary endpoint of the RCT, the percentage of patients who had an RFBM within four hours after ≥2 of the first 4 doses of study drug in the first week of treatment was 62.9% (95% confidence interval [CI], 53.5% to 71.7%) for the MNTX arm and 9.6% (95% CI, 4.9% to 16.6%) for the placebo arm (p<0.0001; see Fig. 2). Patient baseline weight (<62 kg versus ≥62 kg) did not affect the primary endpoint response of MNTX treatment compared with placebo (62.2% versus 7.3% for MNTX versus placebo in the <62 kg group, compared with 63.4% versus 11.0% for MNTX versus placebo in the ≥62 kg group; p<0.0001). Although there were few patients with a baseline body weight >114 kg, the primary endpoint response for this group (60.0% versus 0% for MNTX [n=5] versus placebo [n=5]; p=0.1667) was similar compared with that for patients with a baseline body weight ≤114 kg (63.1% versus 10.1% for MNTX [n=111] versus placebo [n=109]; p<0.0001).


Fixed-Dose Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: Results of a Randomized, Placebo-Controlled Study and Open-Label Extension.

Bull J, Wellman CV, Israel RJ, Barrett AC, Paterson C, Forbes WP - J Palliat Med (2015)

RFBM within four hours after ≥2 of the first 4 doses of MNTX or placebo in the first week of treatment in the RCT. MNTX, methylnaltrexone; RCT, randomized, placebo-controlled trial; RFBM, rescue-free bowel movement.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4492709&req=5

f2: RFBM within four hours after ≥2 of the first 4 doses of MNTX or placebo in the first week of treatment in the RCT. MNTX, methylnaltrexone; RCT, randomized, placebo-controlled trial; RFBM, rescue-free bowel movement.
Mentions: For the primary endpoint of the RCT, the percentage of patients who had an RFBM within four hours after ≥2 of the first 4 doses of study drug in the first week of treatment was 62.9% (95% confidence interval [CI], 53.5% to 71.7%) for the MNTX arm and 9.6% (95% CI, 4.9% to 16.6%) for the placebo arm (p<0.0001; see Fig. 2). Patient baseline weight (<62 kg versus ≥62 kg) did not affect the primary endpoint response of MNTX treatment compared with placebo (62.2% versus 7.3% for MNTX versus placebo in the <62 kg group, compared with 63.4% versus 11.0% for MNTX versus placebo in the ≥62 kg group; p<0.0001). Although there were few patients with a baseline body weight >114 kg, the primary endpoint response for this group (60.0% versus 0% for MNTX [n=5] versus placebo [n=5]; p=0.1667) was similar compared with that for patients with a baseline body weight ≤114 kg (63.1% versus 10.1% for MNTX [n=111] versus placebo [n=109]; p<0.0001).

Bottom Line: Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001).Efficacy results during the OLE study were consistent with the RCT.MNTX demonstrated a favorable safety profile in the RCT and OLE study.

View Article: PubMed Central - PubMed

Affiliation: 1 Four Seasons , Flat Rock, North Carolina.

ABSTRACT

Background: Subcutaneous methylnaltrexone (MNTX), dosed based on body weight, is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); however, fixed-dose administration of MNTX may improve ease of administration.

Objective: The study objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4 trials.

Methods: In a double-blind, randomized, placebo-controlled trial (RCT), patients with advanced illness and OIC received MNTX (8 mg or 12 mg by body weight [38 kg to <62 kg or ≥62 kg, respectively]) or placebo every other day (QOD) for two weeks. Patients completing the RCT could enroll in an open-label extension (OLE) study with MNTX administered as needed (PRN). The primary endpoint was percentage of patients with a rescue-free bowel movement (RFBM) within four hours after ≥2 of the first 4 doses in the first week.

Results: In the RCT, 116 and 114 patients received MNTX and placebo, respectively, and 149 patients continued to the OLE study. The percentage of patients achieving primary endpoint was 62.9% and 9.6% for MNTX and placebo groups, respectively (p<0.0001). Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001). Efficacy results during the OLE study were consistent with the RCT. MNTX demonstrated a favorable safety profile in the RCT and OLE study.

Conclusion: Fixed-dose MNTX administered QOD in the RCT and PRN in the OLE study demonstrated robust efficacy and was well tolerated in treating OIC in patients with advanced illness.

No MeSH data available.


Related in: MedlinePlus