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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

Patient disposition. MNTX, methylnaltrexone; OLE, open-label extension; RCT, randomized, placebo-controlled trial. *Other category includes discontinuation because of investigator and patient request. †Seven patients were enrolled in the OLE study but did not receive any medication.
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Related In: Results  -  Collection


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f1: Patient disposition. MNTX, methylnaltrexone; OLE, open-label extension; RCT, randomized, placebo-controlled trial. *Other category includes discontinuation because of investigator and patient request. †Seven patients were enrolled in the OLE study but did not receive any medication.

Mentions: In the RCT, of the 237 patients randomized, 230 patients received ≥1 dose of the study drug (116 and 114 patients in the MNTX and placebo groups, respectively; see Fig. 1). Of the 156 patients entering the OLE study from the RCT, 149 received ≥1 dose of MNTX. Demographic and baseline characteristics were generally similar between treatment groups in the RCT (see Table 1). In the MNTX group, approximately two-thirds of the patients had a body weight of ≥62 kg and were treated with MNTX 12 mg/day. Five patients in each treatment group weighed >114 kg. The overall patient population (n=230) in the RCT was well balanced between males and females, and the patients were predominantly white (93.9%) with a mean age of 65.5 years. In addition, the most common underlying advanced illness was cancer (66.1%), the median daily morphine equivalent dose was 176.8 mg/d, and the mean duration of OIC was 76.6 weeks. There were no notable differences in demographic and baseline characteristics between the MNTX and placebo groups.


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)

Patient disposition. MNTX, methylnaltrexone; OLE, open-label extension; RCT, randomized, placebo-controlled trial. *Other category includes discontinuation because of investigator and patient request. †Seven patients were enrolled in the OLE study but did not receive any medication.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Patient disposition. MNTX, methylnaltrexone; OLE, open-label extension; RCT, randomized, placebo-controlled trial. *Other category includes discontinuation because of investigator and patient request. †Seven patients were enrolled in the OLE study but did not receive any medication.
Mentions: In the RCT, of the 237 patients randomized, 230 patients received ≥1 dose of the study drug (116 and 114 patients in the MNTX and placebo groups, respectively; see Fig. 1). Of the 156 patients entering the OLE study from the RCT, 149 received ≥1 dose of MNTX. Demographic and baseline characteristics were generally similar between treatment groups in the RCT (see Table 1). In the MNTX group, approximately two-thirds of the patients had a body weight of ≥62 kg and were treated with MNTX 12 mg/day. Five patients in each treatment group weighed >114 kg. The overall patient population (n=230) in the RCT was well balanced between males and females, and the patients were predominantly white (93.9%) with a mean age of 65.5 years. In addition, the most common underlying advanced illness was cancer (66.1%), the median daily morphine equivalent dose was 176.8 mg/d, and the mean duration of OIC was 76.6 weeks. There were no notable differences in demographic and baseline characteristics between the MNTX and placebo groups.

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