Results of a Phase 1 clinical trial showed that the investigational therapy GTP-004 significantly reduced the side effects associated with the myasthenia gravis (MG) medication Mestinon (pyridostigmine).
GT Biopharma, the therapy’s developer, plans to accelerate the development of GTP-004 by initiating a Phase 2 trial in myasthenia gravis patients later this year.
GTP-004 is an investigational combination of Mestinon with ondansetron (brand name Zofran).
Mestinon is used in the treatment of muscle weakness in myasthenia gravis. It is an acetylcholinesterase inhibitor, which prevents the degradation of acetylcholine, increasing its levels and boosting muscle contraction.
However, Mestinon can cause gastrointestinal (GI) side effects, such as diarrhea, nausea, and vomiting. As a result, the dose may have to be lowered, which decreases the therapy’s effectiveness. The use of ondansetron aims to avoid the GI side effects and maintain Mestinon’s efficacy.
The Phase 1 trial, which completed dosing in January, evaluated whether the use of GTP-004 safely reduced GI side effects associated with Mestinon.
Five volunteers took increasing doses of Mestinon, from 30 to 120 mg once a day, in the morning. Once participants reported reaching the first intolerable dose (FID), characterized by dose-limiting GI effects, they stopped taking Mestinon for two to seven days. They then received escalating doses of GTP-004.
FID occurred at 60 mg for two subjects and 90 mg for the third subject. GTP-004 led to a substantial reduction or the complete elimination of GI side events, and all participants tolerated doses as high as 120 mg, the maximum allowed by protocol.
Researchers then assessed whether the improvement in GI side effects with GTP-004 in the three volunteers who reached FID was due to a reduction in blood levels of Mestinon.
Results revealed almost identical blood levels of Mestinon before and after the combination with ondansetron in all three subjects. This led scientists to conclude the reduced side effects were due to a benefit with GTP-004 rather than decreased absorption and blood levels of Mestinon.
“These results provide additional evidence of the ability of GTP-004 to avoid the GI side effects of administering [Mestinon] alone and offer hope to all those suffering from myasthenic syndromes,” Shawn Cross, CEO of GT Biopharma, said in a press release.
“We are working diligently to accelerate this program and be in a position to begin a Phase 2 clinical trial in patients in the third quarter of 2018,” he added.