Renzapride is a
prokinetic agent
A prokinetic agent (also gastroprokinetic agent, gastrokinetic agent or propulsive) is a type of drug which enhances gastrointestinal motility by increasing the frequency or strength of contractions, but without disrupting their rhythm. They are ...
and
antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They m ...
which acts as a full
5-HT4 agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
and partial
5-HT3 antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...
.
It also functions as a
5-HT2B antagonist and has some affinity for the
5-HT2A and
5-HT2C receptors.
Renzapride was being developed by Alizyme plc of the United Kingdom. In May 2016, EndoLogic LLC, a US-based pharmaceutical and medical device company, acquired the US and worldwide patent rights to Renzapride.
Endologic confirmed the cardiac safety of renzapride through a “Thorough QTc” study and sold the rights to Atlantic Healthcare plc in 2019, a specialist pharmaceutical company.
Atlantic Healthcare is focusing on the development of renzapride for the management of gastrointestinal (GI) motility in a number of rare diseases, including systemic scleroderma and cystic fibrosis, both of which are associated with chronic GI motility problems and for which there are no approved therapies.
Clinical trials
In nine diabetic patients with autonomic neuropathy, renzapride reduced the mean lag phase of gastric emptying by 20–26 min at all doses (''P'' < 0.01)
In Phase 2a studies on subjects with constipation Renzapride was shown to accelerate colonic transit (p=0.016 vs placebo P=0.009) (Ref: ATL 1251/001/CL) as well as increase daily stool frequency (p<0.005) (Ref: ATL 1251/025/CL)
Renzapride has been assessed in Phase II clinical trials with a total of 578 patients with constipation-predominant
irritable bowel syndrome
Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
(IBS-C). As compared with placebo, the treatment groups reported better relief of their overall symptoms namely, abdominal pain and discomfort, increase in the number of pain free days, improved stool frequency, consistency and ease of passage of bowel movements. There were no significant differences in the reported Serious Adverse Events between treatment and placebo groups.
In the largest of these Phase II trials, 510 subjects with IBS-C received either 1, 2 or 4 mg QD renzapride, or placebo QD for 12 weeks. The Weekly responder rate based on subject's assessment of whether they had relief from abdominal pain and/or discomfort associated with IBS during weeks 5-12 was 56% (renzapride 4 mg) vs 49% (placebo). For females the treatment effect was larger, 61% (renzapride 4 mg) vs 49% (placebo). Statistically significant effects in favour of renzapride were observed for improvements in stool consistency and increased bowel movements.
In the Phase III clinical trial in IBS-C, 1798 female patients received either 2 or 4 mg Renzapride, or placebo once daily, for 12 weeks. The mean number of months with relief of overall symptoms was 0.6, 0.55 and 0.44 for renzapride 2 mg twice a day, renzapride 4 mg once a day and placebo, respectively, with both renzapride doses being statistically superior to placebo (p=0.004 and p=0.027, respectively). On responder analysis, the proportion of responders was 33.2%, 29.8%, and 24.3% for renzapride 2 mg twice a day, renzapride 4 mg once a day and placebo, respectively.
The 8.9% delta between renzapride 2 mg twice daily and placebo compares favourably with other FDA approved therapies (Ford
).
References
{{Serotonergics
5-HT3 antagonists
Abandoned drugs
Anilines
Benzamides
Chloroarenes
Nitrogen heterocycles
Phenol ethers
Heterocyclic compounds with 2 rings