Author name, year | Drug | Study population and design | Endpoint | Results |
---|---|---|---|---|
Eguchi, 2020 | Lubiprostone | • Population: ≥65 years (80%) • Population type: CC • Sample size: 1,338 • Design: Retrospective single-arm study • Region: Japan | • SBM frequency (no./wk) | Week 2 SBM frequency: mean (SD) • Before: 2.7 (2.7) • After: 5.3 (6.9); p < 0.01 Note: There were 34 (2.5%) patients who did not respond to the 2 weeks treatment with Lubi. |
Fukudo, 2015 | Lubiprostone | • Population: Adults • Population type: CIC • Sample size: 124 • Design: RCT, phase III • Region: Japan | • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • SBM ≤ 48 h • Responder rate (> 4 SBMs/wk) | SBM frequency, mean (SD) at baseline, • Lubi 48 mcg: 1.65 (0.78) • PBO: 1.68 (0.77), p = 0.873 Change from baseline in SBM frequency, mean (SE) • Week 1: Lubi 48 mcg: 3.7 (2.8); PBO: 1.3 (1.8), (p < 0.001) • Week 2: Lubi 48 mcg: 2.74; PBO: 1.33, (p < 0.001) • Week 3: Lubi 48 mcg: 2.75; PBO: 1.51, (p < 0.005) • Week 4: Lubi 48 mcg: 2.56; PBO: 1.62, (p = 0.042) SBM ≤ 24 h (%): • Lubi 48 mg: 58.1%; PBO: 30.6%, (p = 0.004) SBM ≤ 48 h (%): • Lubi 48 mcg: 80.6%; PBO: 64.5%, (p = 0.069) Responder rate (%) • Week 1: Lubi 48 mcg: 75.4%; PBO: 29.0% (p = 0.001) • Week 2: Lubi 48 mcg: 53.4%; PBO: 40.0% (p = 0.196) • Week 3: Lubi 48 mcg: 54.4%; PBO: 37.7% (p = 0.096) • Week 4: Lubi 48 mcg: 54.2%; PBO: 36.7% (p = 0.066) |
Fukudo, 2011 | Lubiprostone | • Population: Adults • Population type: CIC plus IBS-C • Sample size: 170 • Design: RCT phase II (dose-finding study) • Region: Japan | • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • SBM ≤ 48 h | Week 1 Change from baseline in SBM frequency, mean (SE) • Lubi 48 mcg: 6.8 (1.1), (p < 0.0001, vs. PBO) • PBO: 1.5 (0.4) SBM ≤ 24 h (n%) • Lubi 48 mcg: 75%, (p < 0.0001, vs. PBO) • PBO: 26.2% SBM ≤ 48 h (n%): • Lubi 48 mcg: 97.7%, (p < 0.0001, vs. PBO) • PBO: 57.1% |
Johanson, 2008 | Lubiprostone | • Population: Adults • Population type: CC • Sample size: 242 • Design: RCT; phase III • Region: USA | • SBM frequency (no./wk) • SBM ≤ 24 h • SBM ≤ 48 h • Responder rate (≥ 3 SBMs/wk) | SBM frequency, mean (SD) • Baseline: Lubi: 1.37 (0.87); PBO: 1.47 (1.33) • Week 1: Lubi: 5.69; PBO: 3.46 (p = 0.0001) • Week 2: Lubi: 5.06; PBO: 3.18 (p ≤ 0.002) • Week 3: Lubi: 5.25; PBO: 2.84 (p ≤ 0.002) • Week 4: Lubi: 5.30; PBO: 2.91 (p ≤ 0.002) SBM ≤ 24 h (%) • Lubi: 56.7%; PBO: 36.9%; (p = ≤ 0.0024, vs. PBO) SBM ≤ 48 h (%) • Lubi: 80%; PBO: 60.7%; (p = 0.0013, vs. PBO) Responder rate (%) • Week 1: Lubi: 64.7%; PBO: 43.4% (p < 0.004) • Week 2: Lubi: 57.8%; PBO: 36.1% (p < 0.004) • Week 3: Lubi: 56.0%; PBO: 28.7% (p < 0.004) • Week 4: Lubi: 57.8%; PBO: 27.9% (p < 0.004) |
Johanson, 2007 | Lubiprostone | • Population: Adults • Population type: CC • Sample size: 127 • Design: RCT; phase II (dose-ranging study) • Region: USA | • SBM frequency (no./wk) • SBM ≤ 24 h | SBM frequency Week 1 • Lubi 48 mcg: (p = 0.002, vs. PBO) Week 2 • Lubi 48 mcg: (p ≤ 0.020, vs. PBO) SBM ≤ 24 h (%) • Lubi 48 mcg (24 mcg b.d.): 59.4%; (p = 0.009) |
Barish, 2010 | Lubiprostone | •Population: Adults •Population type: CC •Sample size: 237 •Design: RCT; phase 3; global | • Frequency of SBMs (no./wk) • SBM ≤ 24 h (%) • Responder rate (%): • Full responders: (SBM frequency ≥ 4 per week) | Frequency of SBMs •Baseline: Lubi 48 mcg:1.28, PBO: 1.5 (p = 0.0126) •Week 1: Lubi 48 mcg: 5.89, PBO: 3.99 (p < 0.0001) •Week 2: Lubi 48 mcg: 4.96, PBO: 3.55 (p < 0.0487) •Week 3: Lubi 48 mcg: 5.56, PBO: 3.36 (p < 0.0004) •Week 4: Lubi 48 mcg: 5.37; PBO: 3.46 (p < 0.0068) SBM ≤ 24 h (%): •Week 1: Lubi 48 mcg: 61.3% •PBO: 31.4% (p < 0.0001) Responder rate, full responder (n%) •Week 1: Lubi 48 mcg: 72%, PBO: 49%; (p < 0.0001) •Week 2: Lubi 48 mcg: 58%, PBO: 43%; (p = 0.0171) •Week 3: Lubi 48 mcg: 61%, PBO: 36%; (p = 0.0002) •Week 4: Lubi 48 mcg: 60%, PBO: 39%; (p = 0.0002) |
Fukudo, 2019 | Linaclotide | • Population: Adults • Population type: CC • Sample size: 181 • Design: RCT, phase III • Region: Japan | • SBM frequency (no./wk) • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • Responder rate (> 3 SBMs/wk) | Week 1 SBM frequency: mean (95% CI) • Lina 500 mcg: 5.72 (5.10, 6.35) • PBO: 3.19 (2.55, 3.82); p < 0.001 Change from baseline in SBM frequency, mean (95% CI) • Lina 500 mcg: 4.02 (3.39, 4.64) • PBO: 1.48 (0.85, 2.12); p < 0.001 SBM ≤ 24 h (%, 95% CI) • Lina 500 mcg:72.8 (62.6, 81.6); p < 0.001 • PBO: 48.3 (37.6, 59.2) Responder rate: Mean (95% CI). 1st week: • Lina 500 mcg: 83.5 (74.3, 90.5) • PBO: 56.8 (45.8, 67.3); p < 0.001 2nd of 4 weeks: • Lina 500 mcg: 83.5 (74.3, 90.5) • PBO: 64.8 (53.9, 74.7); p = 0.006 3rd of 4 weeks: • Lina 500 mcg: 71.4 (61.0, 80.4) • PBO: 42.0 (31.6, 53.0); p < 0.001 |
Fukudo, 2018 | Linaclotide | • Population: Adults • Population type: CC • Design: RCT; phase II (dose-finding study) • Sample size: 382 • Region: Japan | • SBM frequency (no./wk) • Change from baseline in SBM frequency (no./wk) • Responder rate (%) (> 3 SBMs/wk) | SBM frequency: mean. Week 1 • Lina 500 mcg: 5.58; p < 0.001 • PBO: 3.64 Week 2 • Lina 500 mcg: 5.70; p < 0.001 • PBO: 3.27 Change from baseline in SBM frequency, Mean. Week 1 • Lina 500 mcg: 3.85; p < 0.001 • PBO: 1.91 Week 2 • Lina 500 mcg: 3.96; p < 0.001 • PBO: 1.53 Responder Rate (%): Week 1 • Lina 500 mcg: 77.6%; p = 0.037 • PBO: 61.3% Week 2 • Lina 500 mcg: 82.7%; p = 0.002 • PBO: 60% |
Schoenfeld, 2018 | Linaclotide | • Population: Adults • Population type: CIC • Design: RCT; phase III, (NCT02291679) • Sample size: 1223 • Region: USA | • SBM frequency (no./wk) • Change from baseline in SBM frequency (no./wk) | Week 12 SBM frequency: mean. • Lina 145 mcg: 4.1 • PBO: 2.7 Change from baseline in SBM frequency, mean. • Lina 145 mcg: 2.6; p < 0.0001 • PBO: 1.3 |
Lacy, 2015 | Linaclotide | • Population: Adults • Population type: CIC • Design: RCT; phase IIIb, (NCT01642914) • Sample size: 483 • Region: USA/Canada | • SBM frequency (no./wk) • Change from baseline in SBMs/wk • Change from baseline in days/wk with an SBM • SBM ≤ 24 h | Week 12 SBM frequency: mean • Lina 145 mcg: 5.2* • PBO: 3.3* *Note: Over the 12-week treatment period. Change from baseline in SBM frequency, LS mean • Lina 145 mcg: 3.6; (p < 0.0001, vs. PBO) • PBO: 1.6 Change from baseline in days/week with an SBM: mean • Lina 145 mcg: 2.3; (p < 0.0001, vs. PBO) • PBO: 1.2 SBM ≤ 24 h (%): • Lina 145 mcg: 61.4%; (p < 0.0006, vs. PBO) |
Lembo, 2011a Lembo, 2011b | Linaclotide | • Population: Adults • Population type: CC • Design: RCT (Trial 303); phase III; (NCT00730015) • Sample Size: 642 • Region: USA/Canada | • SBM frequency (no./wk) • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • Increase of ≥ 2 SBMs for 9 of 12 wk | Week 12 SBM frequency: mean • Lina 145 mcg: 5.2 • PBO: 3.2 Change from baseline in SBM frequency, mean • Lina 145 mcg: 3.0; p < 0.001 • PBO: 1.1 SBM ≤ 24 h (%): • Lina 145 mcg: 70% p < 0.001 • PBO: 39.7% Increase of ≥ 2 SBMs for 9 of 12 wk (%) • Lina 145 mcg: 41% p < 0.001 • PBO: 12.9% |
Linaclotide | • Population: Adults • Population type: CC • Design: RCT (Trial 01); phase III; (NCT00765882) • Sample size: 630 • Region: USA/Canada | • SBM frequency (no./wk) • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • Increase of ≥ 2 SBMs for 9 of 12 wk | Week 12 SBM frequency: mean • Lina 145 mcg: 5.3 • PBO: 3.0 Change from baseline in SBM frequency, mean • Lina 145 mcg: 3.4; p < 0.001 • PBO: 1.1 SBM ≤ 24 h (%): • Lina 145 mcg: 64.3%; p < 0.001 • PBO: 39.1 Increase of ≥ 2 SBMs for 9 of 12 wk (%): • Lina 145 mcg: 39% P < 0.001 • PBO: 16.3 | |
Tomie, 2020 | Elobixibat | • Population: Elderly • Population type: CC • Design: RCS • Sample size: 104 • Region: Japan | • SBM frequency (no./wk) • SBM ≤ 24 h • Time to first SBM • Responder rate | Week 2 SBM frequency, mean (SD) • Baseline: 2.86 (1.77) • Elob: 6.08 (4.65); p < 0.001 Subgroup Age: ≤74 years: • Baseline: 2.82 (1.85) • Elob: 6.31 (4.77); p < 0.001 Age: ≥75 years: • Baseline: 2.90 (1.68) • Elob: 5.82 (4.54); p < 0.001 SBM ≤ 24 h (%): • Overall: 78.7% • Aged ≤ 74 years: 78.3%; p = 0.92 • Aged ≥ 75 years: 79.3%; p = 0.92 Time to first SBM, mean (SD) • Week 2: 14.8 (12.6) hrs Responder rate, (n%): • Week 2: 74% |
Kumagai, 2018 | Elobixibat | • Population: Adult • Population type: CC • Design: RCT, phase I (dose-escalating design) • Sample size: 120 • Region: Japan | • SBM ≤ 24 h | Week 2 SBM ≤ 24 h (%) • Elob 10 mg/day: 100% • Elob 15 mg/day: 88.9% • PBO: 40% The time to the first SBM was shorter in the Elob groups than in the PBO |
Nakajima, 2018b | Elobixibat | • Population: Adult • Population type: CC plus IBS-C • Design: RCT, phase IIb (JapicCTI-142,608) • Sample size: 163 • Region: Japan | • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • Time to first SBM | SBM frequency, mean at baseline • 1.6 to 1.8 Week 1 Change from baseline in SBM frequency, mean • Elob 10 mg: 5.7; (p < 0.001, vs. PBO) • Elob 15 mg: 5.6; (p < 0.001, vs. PBO) • PBO: 2.6 SBM ≤ 24 h (%): • Elob 10 mg: 90%; (p < 0.001, vs. PBO) • Elob 15 mg: 93%; (p < 0.001, vs. PBO) • PBO: 48% Time to first SBM, mean • Elob 10 mg: 8.2 h • Elob 15 mg: 8.5 h • PBO: 36.2 h |
Nakajima, 2018a | Elobixibat | • Population: Adult • Population type: CC plus IBS-C • Design: RCT, phase III, (JapicCTI-153,061) • Sample size: 132 • Region: Japan | • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • Responder rate (> 3 SBMs/wk) | Change from baseline in SBM frequency, LS mean (SE), [95% CI] Week 1 • Elob 10 mg: 6·4 (0·6) [5.3–7.6] • PBO: 1.7 (0.2) [1.2–2] • Difference: 4.7(0.6) [3.4–5.9]; p < 0.0001 Week 2 • Elob 10 mg: 5.0 (0.4) [4.2–5.8] • PBO: 1.8 (0.2) [1.3–2.2] • Difference: 3.2(0.5) [2.3–4.1]; p < 0.0001 SBM ≤ 24 h (n %) • Elob 10 mg: 86% • PBO: 41% • Difference: 44%; p < 0.0001 Responder rate (%) Week 1 • Elob 10 mg: 94% • PBO: 60% • Difference: 34% Week 2; p < 0.0001 • Elob 10 mg: 92% • PBO: 63% • Difference: 29%; p < 0.0001 |
Chey, 2011 | Elobixibat | • Population: Adults • Population type: CIC • Design: RCT; phase IIb (NCT01007123) • Sample size: 190 • Region: USA | • Change from baseline in SBM frequency (no./wk) • SBM ≤ 24 h • Time to first SBM | Change from baseline in SBM frequency, LS mean (95% CI) Week 1 • Elob 10 mg: 4.0 (2.9–5.0); p < 0.002 • Elob 15 mg: 5.4 (4.4–6.4); p < 0.001 • PBO: 1.7 (0.7–2.8) SBM ≤ 24 h (%): • Elob 10 mg: 74%, (p = 0.012, vs. PBO) • Elob 15 mg: 75%, (p = 0.012, vs. PBO) • PBO: 45% Time to first SBM, mean • Elob 10 mg: 12 h (p = 0.033, vs. PBO) • Elob 15 mg: 07 h (p = 0.039, vs. PBO) • PBO: 27 h |