纳地美定(Naldemedine)的治疗效果如何？

(Naldemedine) is very effective. The drug can significantly increase the number of bowel movements in patients with opioid-induced constipation (OIC). It has the advantages of having no effect on pain and not causing opioid withdrawal symptoms, providing a new treatment method for OIC patients. However, although the drug has been successfully approved for marketing in the United States, its efficacy in patients from different regions and different races still requires further research. The following is a detailed introduction to the therapeutic effect of Naldemedine.

About Naldemedine

On March 23, 2017, the U.S. FDA approved the marketing of Naldemedine for the treatment of constipation caused by opioids in adult patients with chronic non-cancer pain. The drug was jointly developed by Japan's Shionogi Pharmaceuticals and the U.S. Purdue Pharmaceuticals, with the trade name Symproic.

The role of nadimedine

As a μ-opioid receptor antagonist with peripheral nervous system effects, naldimedine acts on gastrointestinal tissues to reduce the constipating effects of opioids. Nadimedine is a derivative of naltrexone. The introduction of side chains increases the molecular weight and polar surface area of ​​naldimedine, reducing its ability to pass through the blood-brain barrier, thereby reducing interference with opioid analgesics acting on the central nervous system.

Nadimedine Phase I Clinical Trial

Two randomized, double-blind, controlled phase I studies examined the safety, tolerability, and pharmacokinetics of naldimedine. Healthy Japanese male subjects aged 20 to 39 years were included in this study. The research results found that the preliminary metabolite of naldemedine is nOr-naldemedine. Both studies showed that drug-related adverse reactions (TEAEs) were not dose-related and were mainly gastrointestinal reactions; at the same time, the study found that the dose range of 0.1 to 100 mg naledimedine showed a certain exposure, but 3 to 30 mg·d-1 naledimedine had better safety and tolerability.

Nadimedine Phase II Clinical Trial

In 2017, Webster et al. conducted a randomized, double-blind, controlled phase II clinical study. 244 patients who had been taking opioids for a long time to treat constipation caused by chronic non-cancer pain were included in the study. The results showed that: compared with the placebo group, the weekly SBM frequency of patients in the 0.2 and 0.4 mg naldimedine groups was significantly increased (P=0.001 4, P=0.000 3), while the patients in the 0.1 mg naldimedine group showed no significant difference (P=0.1461). Adverse reactions are generally mild to moderate and increase with dose.

Nadimedine Phase III Clinical Trial

Two phase III double-blind randomized controlled clinical trials included patients aged 18 to 80 years old with non-cancer pain OIC (the number of participants in the two studies were 1547 and 2553 respectively, and the study period was 12 weeks). The subjects were randomly divided into a 0.2 mg naldimedine combination placebo group, and their efficacy, safety and tolerability were evaluated.

Both studies showed that the response rate of patients in the naldimedine group was significantly higher than that of the placebo group, and the number of weekly SBMs was significantly increased. It was also found that the TEAEs in both studies were similar to those in the placebo group. TEAEs occurred in >5% of subjects, mainly manifesting as abdominal pain and diarrhea, and were well tolerated. No patients in the nadimedine group showed obvious withdrawal symptoms in either study.

Nadimedine adverse reactions

Naldemedine manifests itself as opioid withdrawal symptoms, with common gastrointestinal reactions such as abdominal pain, diarrhea, nausea and vomiting, and non-gastrointestinal symptoms such as chills, sweating, and tachycardia. It is worth noting that taking this drug by pregnant women may cause the fetus to produce opioid receptor withdrawal symptoms.

References

[1] Lanzhihui, Yan Feng$. Pharmacological effects and clinical evaluation of Naldemedine in the treatment of constipation [J]. Journal of Clinical Drug Therapy, 2017, 15(08): 6-9.

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