TD-1211 demonstrates a durable increase in bowel movement frequency and return toward normal bowel function in a 5-week Ph2b Opioid-Induced Constipation (OIC) study

Systematic review with meta‐analysis: efficacy and safety of treatments for opioid‐induced constipation

“…Increase in spontaneous bowel movements per week (Figure 2) Overall analysis included 22 studies and demonstrated an increase of 1.1 spontaneous bowel movements /week (95% CI 0. 78‐1.41), I 2 99% 45,48‐52,54‐56,59,65,66,69‐71,73‐79 Subgroup analysis demonstrated the greatest improvement in spontaneous bowel movements (≥1 increase in spontaneous bowel movements /week) with naldemedine, naloxone, naloxegol 25 mg, linaclotide, alvimopan and axelopran.…”

“…There were 1656 unique articles found through the literature search. Of these, 266 abstract and full‐text reviews were completed, resulting in a total of 35 eligible randomised controlled trials at low risk of bias enrolling 13 566 patients 45‐79 who were included in the systematic review and meta‐analysis. (Figure 1) The kappa statistic for the final selection of studies was 0.94.…”

“…Axelopran resulted in an increase of 1.7 complete spontaneous bowel movements per week (95% CI 0. 74‐1.97), I 2 NA 79 Bristol stool form scale—based on the 7‐point scale (Figure S3).…”

“…87 [95% CI 1.42‐2. 47], I 2 0%), 65,66 naloxegol 12.5 mg (OR 1.56 [95% CI 1.18‐2.06], I 2 0%) 65,66 and axelopran (OR 3.63 [95% CI 1.63‐8.1], I 2 NA), 79 resulted in the highest odds ratio of meeting the FDA spontaneous bowel movements endpoint. Odds ratios for lubiprostone (1 trial OR 1.65 [95% CI 1.01‐2.51]) 70 was significant, but that for linaclotide (1 trials OR 1.…”

“…Only one trial detailed the serious adverse events, which included pneumonia, bile duct obstruction, cholecystitis, grand mal convulsion and fall complicated by skin laceration 62 Abdominal pain (Figure 4) Overall, PAMORAs, promotility agents and secretory agents had an OR 2.24 (95% CI 1.79‐2.8), I 2 30% of resulting in abdominal pain as compared to placebo 45,50‐53,57,58,60,62,64‐66,68‐70,72,74‐81 Subgroup analysis—Lubiprostone [OR 5.56 (95% CI 2‐15.41), I 2 21%], 69,70,72 methylnaltrexone (OR 2.55 [95% CI 1.27‐5.13], I 2 65%), 52,53,57,58,81 naloxegol 25 mg (OR 3.02 [95% CI 1.87‐4.88], I 2 0%) and naldemedine (OR 3.19 [95% CI 2.07‐4.92], I 2 0%) 45,50,51,80 reported the highest rates of abdominal pain compared to placebo. The lowest rates of abdominal pain were seen with combination oxycodone/naloxone (OR 1.28 [95% CI 0.28‐5.87], I 2 71%) 60,62,64 and prucalopride (OR 1.38 [95% CI 0.45‐4.22], I 2 NA%) 74 …”