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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

Kaplan-Meier curves for the time to bowel movement after first dose of the study drug in the MNTX and placebo groups in the RCT. MNTX, methylnaltrexone; RCT, randomized, placebo-controlled trial; RFBM, rescue-free bowel movement.
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f3: Kaplan-Meier curves for the time to bowel movement after first dose of the study drug in the MNTX and placebo groups in the RCT. MNTX, methylnaltrexone; RCT, randomized, placebo-controlled trial; RFBM, rescue-free bowel movement.

Mentions: Significant differences favoring MNTX were observed for all secondary efficacy endpoints measured in the RCT (see Table 2). The time to RFBM after the first dose in the RCT was rapid in the MNTX group, with a median time of 0.8 hour versus 23.6 hours for the placebo group (p<0.0001; see Fig. 3). The median time to first RFBM after the first dose was similar in both weight groups (0.8 hour versus 24.5 hours for MNTX versus placebo in the <62 kg group compared with 0.8 hour versus 22.2 hours for MNTX versus placebo in the ≥62 kg group; p<0.0001). In addition, median times to first RFBM within 24 hours after each dose were significantly shorter in patients in the MNTX group compared with patients in the placebo group (p<0.005 after the first, third, fourth, fifth, sixth, and seventh dose). Efficacy during the 10-week OLE study (see Table 3) was generally consistent with results from the two-week RCT.


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)

Kaplan-Meier curves for the time to bowel movement after first dose of the study drug in the MNTX and placebo groups 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

f3: Kaplan-Meier curves for the time to bowel movement after first dose of the study drug in the MNTX and placebo groups in the RCT. MNTX, methylnaltrexone; RCT, randomized, placebo-controlled trial; RFBM, rescue-free bowel movement.
Mentions: Significant differences favoring MNTX were observed for all secondary efficacy endpoints measured in the RCT (see Table 2). The time to RFBM after the first dose in the RCT was rapid in the MNTX group, with a median time of 0.8 hour versus 23.6 hours for the placebo group (p<0.0001; see Fig. 3). The median time to first RFBM after the first dose was similar in both weight groups (0.8 hour versus 24.5 hours for MNTX versus placebo in the <62 kg group compared with 0.8 hour versus 22.2 hours for MNTX versus placebo in the ≥62 kg group; p<0.0001). In addition, median times to first RFBM within 24 hours after each dose were significantly shorter in patients in the MNTX group compared with patients in the placebo group (p<0.005 after the first, third, fourth, fifth, sixth, and seventh dose). Efficacy during the 10-week OLE study (see Table 3) was generally consistent with results from the two-week RCT.

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