Peptide education
Plecanatide
Trulance · SP-304
Plecanatide is an oral prescription peptide that acts in the intestine. Its US product, Trulance, is approved for chronic idiopathic constipation and irritable bowel syndrome with constipation in adults.
Placebo-controlled trials support the two adult indications, but not every participant responded. Diarrhea can be severe, and the label has a boxed warning about serious dehydration in pediatric patients.
Overview
Quick answer
Trulance is an adult medication. Its label contraindicates use in children under 6 and says to avoid use from age 6 to under 18. Pediatric safety and effectiveness have not been established.
What is plecanatide approved for?
Trulance is approved in the United States for adults with chronic idiopathic constipation or IBS-C. Its safety and effectiveness have not been established in people under 18.
How does it work?
Plecanatide resembles the body's uroguanylin peptide and activates guanylate cyclase-C at the intestinal surface. This increases intestinal fluid secretion and helps move stool.
What dose appears on the US label?
The label specifies a 3 mg tablet by mouth once daily for either adult indication, with or without food. Some trials also studied 6 mg, which is not the labeled Trulance dose. This is label context, not individual treatment advice.
What is the most important safety warning?
Trulance is contraindicated under age 6 and should be avoided from age 6 to under 18. It is also contraindicated with known or suspected mechanical gastrointestinal obstruction. Severe diarrhea can require interruption of treatment and rehydration.
Evidence
Evidence snapshot
Over 12 weeks, 21.0% taking 3 mg and 10.2% taking placebo met a durable complete spontaneous bowel-movement response definition.
Combined pain and bowel-movement response was higher with 3 mg than placebo in both 12-week trials, although response rates differed between studies.
The label contraindicates treatment below age 6 and advises avoiding it from age 6 to under 18. Its boxed warning addresses serious dehydration.
Diarrhea was the most common adverse event in the cited constipation and IBS-C trials and can sometimes be severe.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Plecanatide helps adults with chronic idiopathic constipation. | A 12-week randomized trial found a higher durable bowel-movement responder rate with the 3 mg dose than with placebo. | Supported for the studied adult population and outcome. A response on this strict measure was not achieved by most participants. |
| Plecanatide improves both pain and bowel symptoms in IBS-C. | In two randomized adult trials, more participants receiving 3 mg met a combined abdominal-pain and bowel-movement endpoint than those on placebo. | Supported at the group level in the studied adults, with response varying across trials and individuals. |
| Minimal absorption means it is safe for children. | Pediatric safety and effectiveness have not been established. The boxed warning describes deaths from dehydration in young juvenile mice and sets age-specific restrictions. | Incorrect. Low blood levels do not prevent serious intestinal fluid loss. |
| A higher trial dose is necessarily the labeled dose. | The adult trials tested both 3 mg and 6 mg, while the US label specifies 3 mg once daily. | Trial doses and approved dosing are different kinds of evidence and should not be substituted for clinical direction. |
Bottom line
Main takeaway
Trulance is an adult prescription tablet for specific constipation disorders. The main side effect is diarrhea, which can become severe.
Check the diagnosis, patient age, food instructions, and contraindications for each product. A shared receptor does not make labels interchangeable.
The chronic constipation trial measured durable bowel-movement response. The IBS-C trials required pain and bowel-movement improvement together. These are different endpoints, not directly comparable success rates.
Identity
What it is
Plecanatide is a 16-amino-acid structural analog of uroguanylin, an intestinal signaling peptide. Trulance is supplied as a 3 mg oral tablet.
The approved uses are chronic idiopathic constipation and IBS-C in adults. The former is constipation without an identified cause; IBS-C also involves abdominal symptoms.
Use context
Routes, doses, and cycle patterns
Trulance is taken once daily with or without food. Clinical trials also studied a higher dose than the US label specifies.
Human studies and product labels
Adult Trulance label
- Context
- Chronic idiopathic constipation or IBS-C
- Route
- Oral tablet
- Amount
- 3 mg
- Frequency
- Once daily
The label provides alternative administration instructions for patients who cannot swallow the tablet whole or who have a feeding tube.
Adult chronic constipation trial
- Context
- Randomized, placebo-controlled phase 3 trial
- Route
- Oral
- Amount
- 3 mg or 6 mg
- Frequency
- Once daily
- Duration
- 12 weeks
The 6 mg research arm is not the US labeled dose; the study does not set an individual course length.
Adult IBS-C trials
- Context
- Two randomized, placebo-controlled phase 3 trials
- Route
- Oral
- Amount
- 3 mg or 6 mg
- Frequency
- Once daily
- Duration
- 12 weeks
Trial outcomes are for defined adult IBS-C populations and response criteria.
Research
Research evidence
Adult phase 3 trials studied chronic idiopathic constipation and IBS-C separately. In each setting the 3 mg group had a higher responder rate than placebo. The measures and populations differed, so the percentages should not be treated as a head-to-head comparison or a prediction for one person.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Adult chronic idiopathic constipation phase 3 trial | 1,394 adults randomized with chronic idiopathic constipation | Randomized, double-blind, placebo-controlled trial for 12 weeks | Oral plecanatide 3 mg or 6 mg daily | Durable response occurred in 21.0% of the 3 mg group and 10.2% of the placebo group. The response required at least three complete spontaneous bowel movements per week and an increase of at least one from baseline, for at least 9 of 12 weeks including at least 3 of the last 4 weeks. | The trial lasted 12 weeks and assessed a specific durable endpoint. The 6 mg research dose is not the labeled dose. Diarrhea occurred in 5.9% of the 3 mg group and 1.3% of placebo participants. | Strong human evidence for studied adult constipation |
| Two adult IBS-C phase 3 trials | 2,189 adults randomized across both trials | Randomized, double-blind, placebo-controlled trials for 12 weeks | Oral plecanatide 3 mg or 6 mg daily | The combined response at 3 mg was 30.2% versus 17.8% with placebo in one trial and 21.5% versus 14.2% in the other. Response required at least 30% less abdominal pain and at least one additional complete spontaneous bowel movement per week in the same week for at least 6 of 12 weeks. | Most participants did not meet the combined endpoint. Across the trials, diarrhea occurred in 4.3% of the 3 mg group and 1.0% of the placebo group. | Strong human evidence for studied adult IBS-C |
Cautions
Safety and unknowns
- Trulance is contraindicated in children under 6 and should be avoided from age 6 to under 18. The boxed warning refers to deaths from dehydration in young juvenile mice, not deaths observed in a pediatric trial.
- Known or suspected mechanical gastrointestinal obstruction is a contraindication. Severe or unusual abdominal symptoms require clinical assessment rather than an assumption that they are ordinary constipation.
- Diarrhea may be severe. The label advises stopping Trulance and contacting a healthcare provider right away if severe diarrhea occurs; it calls for rehydration and suspension of dosing.
- Available pregnancy data are insufficient to identify a drug-associated risk. Minimal systemic absorption should not be treated as proof of safety for every pregnancy or breastfeeding situation.
Mechanism
How it is proposed to work
Plecanatide activates an intestinal receptor that increases fluid secretion into the bowel, helping stool move through it.
GC-C activation increases cyclic GMP. Intracellular signaling stimulates chloride and bicarbonate secretion largely through CFTR, increasing intestinal fluid and accelerating transit.
The label describes reduced activity of pain-sensing nerves in animal models. Adult IBS-C trials separately measured changes in abdominal pain and bowel movements; the animal mechanism alone does not prove a clinical response.
Details
Technical details
Sources
References
- 1.
FDA. Trulance prescribing information
US indications, dosing, pediatric warning, contraindications, safety, and clinical studies.
- 2.
PubMed. A randomized phase 3 trial of plecanatide in chronic idiopathic constipation
doi:10.1038/ajg.2016.611 PMID:28169285 NCT01982240
Placebo-controlled adult chronic idiopathic constipation trial, including 3 mg and 6 mg groups.
- 3.
PubMed. Plecanatide in irritable bowel syndrome with constipation: two phase 3 randomized trials
doi:10.1038/s41395-018-0026-7 PMID:29545635
Two placebo-controlled adult IBS-C trials with 3 mg and 6 mg treatment groups.