CHAMGAP
APPROVEDReviewed and approved by the Chamgap Editorial Team (2026-07-24). The draft was written by AI, the existence of all 2 cited sources was verified at the original page, and the verdict passed blind grading and adversarial audit. Methodology v0.6.
Verdict No. 1845 · Search date 2026-07-24 · Methodology v0.6

Naldemedine,
does it really help with Improvement of opioid-induced constipation in chronic noncancer pain?

30-Second Summary
C
Evidence Grade C · 58 · Safety caution
Naldemedine improves opioid-induced constipation response, but confirmatory evidence is confined to the manufacturer program
Diarrhea is common, and abdominal pain or nausea can occur. Patients with bowel obstruction risk or a vulnerable bowel wall require avoidance or close supervision because of perforation risk, and uncommon opioid withdrawal symptoms should be monitored.
What the
research shows
Naldemedine is rated C. Two large placebo-controlled trials increased spontaneous-bowel-movement responders, but all decisive evidence came from the Shionogi development program. Response was 47.6% versus 34.6% in COMPOSE-1 and 52.5% versus 33.6% in COMPOSE-2.
What the
ads claim
It can be marketed like a general laxative, but opioid-induced constipation is a cause-specific condition. Evidence from functional constipation or IBS-C was not used.
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Useful facts when choosing a product

  • COMPOSE-1 randomized 547 and analyzed 545; COMPOSE-2 randomized 553 and analyzed 550.
  • The responder definition required at least three weekly spontaneous bowel movements and at least one above baseline during nine of 12 weeks and three of the final four.
Gap Measurement · Verdict 1845 · C 58
What advertising claims
What independent, higher-quality research supports
△ GAP
01

What the research actually shows

COMPOSE-1 randomized 547 and analyzed 545 by intention to treat; response was 47.6% versus 34.6%, difference 13.0 percentage points, 95% CI 4.8 to 21.3, P=0.002, so the primary endpoint succeeded. COMPOSE-2 randomized 553 and analyzed 550; response was 52.5% versus 33.6%, difference 18.9 points, 95% CI 10.8 to 27.0, P<0.0001, also successful. A responder had at least three spontaneous bowel movements weekly and at least one more than baseline for at least nine of 12 weeks and three of the final four weeks. Pain intensity and opioid dose did not worsen clinically, supporting preserved analgesia. Both trials were Shionogi-sponsored. verdict 1573, which is B with 69 points, concerns linaclotide for chronic idiopathic constipation, while verdict 1632, which is B with 70 points, concerns tenapanor for IBS-C; those are different constipation types and their evidence was not transferred.

02

Why this is classified as C (58)

P, R1, I0, E+, and B0 derive C with 58 points under the single-manufacturer-program ceiling.

Counterpoint. The evidence applies to constipation during stable opioid treatment, not general chronic constipation.

Rejudgment record. Cross-check applied — Two confirmatory trials reproduced sustained spontaneous-bowel-movement response, but all decisive evidence came from one manufacturer program

Scoring profile behind this grade
EndpointPPatient-reported treatment goal - the symptom is the goal
ReplicationR1Single confirmatory trial
IndependenceI0Evidence comes only from manufacturer studies
Effect sizeE+Meets the clinically important threshold

The scoring table and the verdict agree (C).

Sub-claim grades by effect

This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.

Effect (sub-claim)GradeBasis
Sustained spontaneous-bowel-movement response over 12 weeksCBoth confirmatory trials succeeded, but all came from the manufacturer program.
Increase in weekly spontaneous bowel movementsCMultiple manufacturer trials and a meta-analysis were positive.
Constipation improvement while preserving analgesiaCPain intensity and opioid dose did not worsen clinically.

Cross-check — Codex and Claude

This verdict was drafted by Codex through literature review and source-existence checks, cross-checked through blind grading and adversarial audit, and settled by reapplying the methodology boundary rules. Cases with split grades were resolved through rejudgment.
03

Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Hale M et al. COMPOSE-1, 2017Twelve-week multicenter randomized double-blind placebo-controlled phase 3 trial545Manufacturer sponsorship by Shionogi Inc. with employee coauthorsProportion of sustained spontaneous-bowel-movement responders47.6% versus 34.6%, difference 13.0 points (95% CI 4.8 to 21.3), P=0.002; primary endpoint succeededKey confirmatory trial
Hale M et al. COMPOSE-2, 2017Twelve-week multicenter randomized double-blind placebo-controlled phase 3 trial550Manufacturer sponsorship by Shionogi Inc. with employee coauthorsProportion of sustained spontaneous-bowel-movement responders52.5% versus 33.6%, difference 18.9 points (95% CI 10.8 to 27.0), P<0.0001; primary endpoint succeededReplication within the same program
§

Receipt — 2 References

All 2 cited sources were verified for existence at the original page (as of 2026-07-24).

Hale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol. 2017;2(8):555-564. PMID: 28576452. DOI: 10.1016/S2468-1253(17)30105-X.
checked
Song X, Wang D, Qu X, Dong N, Teng S. A meta-analysis of naldemedine for the treatment of opioid-induced constipation. Expert Rev Clin Pharmacol. 2019;12(2):121-128. PMID: 30652502. DOI: 10.1080/17512433.2019.1570845.
checked
Draft and rewrite: Codex (AI) · Verification: Codex blind grading and adversarial audit · Final adjudication: Claude
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-07-24 · Corrections: none

Cite this verdict

Naldemedine x improvement of opioid-induced constipation Evidence Grade C card
[Chamgap] Naldemedine x improvement of opioid-induced constipation — Evidence Grade C·58. 2 cited sources checked. Source: https://chamgap.com/en/verdicts/gut/naldemedine-opioid-induced-constipation-sbm-response/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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What this document does and does not do

Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.