PMID-28169285 – Plecanatide Phase III CIC Trial
Miner PB Jr, Koltun WD, Wiber GJ, et al. "A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation," Am J Gastroenterol, 2017;112(4):613-621.
Quick Reference
| Property | Value |
|---|---|
| PMID | 28169285 |
| DOI | 10.1038/ajg.2016.611 |
| Year | 2017 |
| Journal | American Journal of Gastroenterology |
| Study Type | Randomized Controlled Trial (Phase III) |
| Evidence Level | I |
| Sample | n=1,394 patients with CIC |
| Peptide(s) Studied | Plecanatide |
Key Findings
- Plecanatide 3 mg and 6 mg both significantly increased durable overall CSBM responder rates vs placebo (21.0% and 19.5% vs 10.2%; P<0.001 for both)
- Both doses significantly improved stool frequency, stool consistency, and straining
- Onset of effect observed within the first week of treatment
- Adverse event rates were similar across treatment and placebo groups
- Diarrhea was the most common treatment-related adverse event (5.9% for 3 mg, 1.3% for 6 mg vs 1.3% placebo)
- This pivotal trial supported FDA approval of plecanatide (Trulance) in 2017
Study Design
Multicenter, randomized, double-blind, placebo-controlled Phase III trial. Patients with CIC (modified Rome III criteria) were randomized 1:1:1 to plecanatide 3 mg, plecanatide 6 mg, or placebo taken once daily for 12 weeks. Primary endpoint: durable overall CSBM responder (>=3 CSBMs/week and increase of >=1 CSBM from baseline for >=9 of 12 treatment weeks).
Limitations
- 12-week duration may not capture long-term efficacy/safety
- Relatively modest absolute response rates (21% vs 10%)
- Industry-sponsored trial (Synergy Pharmaceuticals)
- Predominantly female population; generalizability to males uncertain
- No active comparator arm
Clinical Relevance
This pivotal Phase III trial established plecanatide as an effective GC-C agonist for CIC, leading to FDA approval. Unlike linaclotide, plecanatide was designed to mimic endogenous uroguanylin with pH-dependent activation in the proximal small intestine, potentially offering a more physiological approach. The low diarrhea rate at both doses compared favorably with linaclotide, suggesting improved tolerability. This gives clinicians a second GC-C agonist option for patients who may not tolerate linaclotide.
Related
#research #RCT #evidence-level-I #gastrointestinal #plecanatide