Efficacy and safety of lubiprostone in patients with opioid-induced constipation: Phase 3 study results and pooled analysis of the effect of concomitant methadone use on clinical outcomes

Egilius L.H. Spierings, Douglas A. Drossman, Byron Cryer, M. Mazen Jamal, Taryn Losch-Beridon, Shadreck M. Mareya, Martin Wang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective. The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo- controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response. Methods. In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24mcg or placebo twice daily for 12weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks. Results. In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P50.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P50.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P50.692). The safety profile of lubiprostone was unaffected by methadone use. Conclusions. The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.

Original languageEnglish (US)
Pages (from-to)1184-1194
Number of pages11
JournalPain Medicine (United States)
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2018

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Methadone
Constipation
Opioid Analgesics
Safety
Placebos
Lubiprostone
Therapeutics
Chronic Pain

Keywords

  • Bowel dysfunction
  • Constipation
  • Methadone
  • Opioid
  • Pain

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Efficacy and safety of lubiprostone in patients with opioid-induced constipation : Phase 3 study results and pooled analysis of the effect of concomitant methadone use on clinical outcomes. / Spierings, Egilius L.H.; Drossman, Douglas A.; Cryer, Byron; Jamal, M. Mazen; Losch-Beridon, Taryn; Mareya, Shadreck M.; Wang, Martin.

In: Pain Medicine (United States), Vol. 19, No. 6, 01.06.2018, p. 1184-1194.

Research output: Contribution to journalArticle

Spierings, Egilius L.H. ; Drossman, Douglas A. ; Cryer, Byron ; Jamal, M. Mazen ; Losch-Beridon, Taryn ; Mareya, Shadreck M. ; Wang, Martin. / Efficacy and safety of lubiprostone in patients with opioid-induced constipation : Phase 3 study results and pooled analysis of the effect of concomitant methadone use on clinical outcomes. In: Pain Medicine (United States). 2018 ; Vol. 19, No. 6. pp. 1184-1194.
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abstract = "Objective. The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo- controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response. Methods. In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24mcg or placebo twice daily for 12weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks. Results. In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P50.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P50.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P50.692). The safety profile of lubiprostone was unaffected by methadone use. Conclusions. The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.",
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T2 - Phase 3 study results and pooled analysis of the effect of concomitant methadone use on clinical outcomes

AU - Spierings, Egilius L.H.

AU - Drossman, Douglas A.

AU - Cryer, Byron

AU - Jamal, M. Mazen

AU - Losch-Beridon, Taryn

AU - Mareya, Shadreck M.

AU - Wang, Martin

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N2 - Objective. The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo- controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response. Methods. In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24mcg or placebo twice daily for 12weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks. Results. In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P50.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P50.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P50.692). The safety profile of lubiprostone was unaffected by methadone use. Conclusions. The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.

AB - Objective. The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo- controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response. Methods. In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24mcg or placebo twice daily for 12weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks. Results. In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P50.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P50.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P50.692). The safety profile of lubiprostone was unaffected by methadone use. Conclusions. The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.

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KW - Constipation

KW - Methadone

KW - Opioid

KW - Pain

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