Company: GHRS
Filing Date: 2025-02-27
Form Type: 20-F
Source: 0001140361-25-006175
Chunk: 31

Company: GH Research PLC
Filing Date: 2025-02-27
Form: 20-F
Item: Item 4
Chunk 31
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22 of 42 subjects (52%) who received GH002 and in 5 of 14 subjects (36%) who received placebo in the single-dose part, and in 4 of 8 subjects (50%) who received GH002 in the IDR part. The majority of TEAEs were mild. In the single-dose part, in subjects who received GH002, the most common TEAEs reported were: fatigue (in 6 participants), nausea (in 5 participants), dizziness (in 4 participants), vomiting and abdominal pain (each in 3 participants), emotional distress, head discomfort, headache, pain in extremity, muscles spasms, and grunting (each in 2 participants). In the IDR part, the most common TEAEs reported were: headache (in 2 participants), head discomfort, nausea, and vomiting (each in 1 participant).
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No clinically relevant changes were observed in the safety laboratory analyses and ECG. With the exception of a temporary, non-clinically relevant increase in heart rate and blood pressure shortly after administration of GH002, no noteworthy changes in vital parameters occurred.
 
Potent PD effects as assessed by psychoactive effect (PsE) intensity were observed across single dose levels and the IDR, with an ultra-rapid onset of PsE and a short duration of the psychoactive experience (generally five to 30 minutes). The PK profile of GH002 was generally dose-linear and correlated with the ultra-rapid profile of the PsE. The analyses of the PK/PD relationship and other secondary endpoints are ongoing and awaited to inform the further clinical development strategy for GH002.
 
Conclusions
 
Intravenous administration of GH002 without additional psychological support before or after dosing, was observed to be well tolerated at the investigated single dose levels and in the IDR with intra-subject dose escalation with a scheduled 1-hour dose interval between doses, and potent and ultra-rapid PD effects as assessed by PsE intensity were observed.
Nonclinical Experience
 
Mebufotenin in vitro and in vivo data from published academic literature allowed initiation of our clinical trials GH001-HV-101, GH001-HV-103 and GH001-TRD-102. We have advanced a nonclinical study program with additional in vitro and in vivo toxicology studies as well as safety pharmacology studies, including studies evaluating genotoxicity and cardiotoxicity with our high-purity active pharmaceutical ingredient, or API, and an inhalation toxicology study in rats