Characteristics of Studies Comparing Novel Medications With Placebo
| Study, country | Comparison | Design | Eligible population | Constipation criteria | Intervention and duration | Number of patients and mean age | Primary outcome | Results |
|---|---|---|---|---|---|---|---|---|
| Camilleri et al36 (2009), USA and Belgium | Prucalopride vs Placebo | Randomized, double-blind, Phase II, placebo-controlled, dose escalation study | Elderly (> 65 yr) patients with constipation residing in a nursing facility | Patients who had a history of constipation, having received treatment for constipation at any time during the 4 wk preceding entry into the study |
A: Placebo B: Prucalopride 0.5 mg qd C: Prucalopride 1 mg qd D: Prucalopride 2 mg qd 4 wk |
A: 18 (F 13) B: 21 (F 18) C: 24 (F 17) D: 26 (F 17) Mean age (range) A: 85.4 (71-98) yr B: 84.4 (75-98) yr C: 82.6 (69-96) yr D: 81.7 (65-94) yr |
Serious AEs Discontinuation d/t AEs QTc prolongation 24 hr Holter monitoring |
See Table 4 |
| Müller-Lissner et al37 (2010), Germany and Belgium | Prucalopride vs Placebo | Multicenter, parallel-group, placebo-controlled Phase III trial | Chronic constipation patients aged > 65 yr | Two or fewer SCBMs per wk in the past 6 mo and one or more of the following for at least a quarter of the symptoms |
A: Placebo B: Prucalopride 1 mg qd C: Prucalopride 2 mg qd D: Prucalopride 4 mg qd 4 wk |
A: 72 (F 42) B: 76 (F 58) C: 75 (F 51) D: 80 (F 60) Mean age (range) A: 76.0 (65-94) yr B: 76.7 (65-92) yr C: 75.6 (64-91) yr D: 77.1 (65-95) yr |
Percentage of patients with ≥ 3 SCBM per wk SBMs/wk |
A 26.1% B 42.1% C 43.8% D 48.7% A 4.2 → 5.1B 4.5 → 6.9a C 4.1 → 6.0 D 4.3 → 6.2 |
| Ueno et al38 (2006), USA | Lubiprostone vs Placebo | Pooled analysis of elderly subjects in 3 RCTs | Chronic constipation patients aged ≥ 65 yr | Rome II criteria for functional constipation |
A: Lubiprostone 24 mg bid B: Placebo 4 wk |
A: 26 B: 31 Mean age not specified |
Additional SBMs/wk compared with baseline Stool consistency and straining AEs |
A: 4.6-5.4B:1.3-2.3 Consistency and straining improved in lubiprostone group See Table 4 |
| Nakajima et al39 (2019), Japan | Elobixibat vs Placebo | Post hoc analysis of randomized, placebo-controlled, phase 3 trials | Patients with severe constipation | ≤ 2 SBMs per wk and ≤ 3 Bristol Stool Form Scale score |
A: elobixibat 10 mg qd B: Placebo 2 wk |
A: 69 (elderly 6) B: 63 (elderly 5) |
Additional SBMs/wk compared with placebo |
Patients < 65: 4.5 (3.3-5.8) Patients ≥ 65: 6.0 (1.8-10.2) |
| Menees et al40 (2020), USA | Plecanatide vs Placebo | Pooled analysis of 4 RCTs | Chronic constipation and IBS-C | Rome III criteria |
A: Placebo B: Plecanatide 3 mg qd C: Plecanatide 6 mg qd 12 wk |
A: 162 B: 150 C: 138 Mean age of all patients 70.0 (4.3) yr |
AEs SCBMs/wk SBMs/wk |
See Table 4 A 1.56 (0.26) B 2.63 (0.27)b C 2.07 (0.29) A 1.90 (0.32) B 3.27 (0.33)b C 2.61 (0.36) |
a
F, female; qd, once a day; bid, 2 times a day; AEs, adverse effects; QTc, corrected QT interval; SCBMs, spontaneous complete bowel movements; SBMs, spontaneous bowel movements; RCTs, randomized controlled trials; IBS-C, irritable bowel syndrome constipation type.