Abstract
Study design:
Single centre, single ascending dose study.
Objectives:
To compare the pharmacokinetics and assess the safety of capromorelin, a compound that has potential to treat constipation following spinal cord injury (SCI), in groups of able-bodied and SCI volunteers.
Setting:
Local population from Victoria, Australia.
Methods:
Following initial screening and baseline blood collections, participants received ascending oral doses (20, 50 and then 100âmg at least 1-week apart) of capromorelin after pre-dose blood collection, followed by blood collections over the following 12âh for pharmacokinetic analysis and 1-week and 4-week follow-up blood collections for safety evaluations. Blood pressure and heart rate were monitored.
Results:
No serious adverse events were recorded following any dose in either the able-bodied group or the SCI group. There were no abnormal blood pressure or heart rate changes. Minor adverse events resolved quickly without the need for treatment. Pharmacokinetic behaviour was broadly similar between groups, with both exhibiting dose-dependent increases in Cmax and AUC0ââ. The SCI participants showed greater variance in pharmacokinetic parameters and had a slightly delayed Tmax and half-life.
Conclusion:
Capromorelin at the doses tested was safe and well tolerated in both SCI and able-bodied participants and also showed similar pharmacokinetics with dose-dependent increases in concentration and drug exposure.
Sponsorship:
Support for the study was provided by the Victorian State Government Transport Accident Commission.
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Acknowledgements
The authors gratefully acknowledge the Victorian State Government Transport Accident Commission, through the Institute for Safety, Compensation and Recovery Research, for funding the study, all participants including relatives and caregivers of SCI participants for their cooperation, SCI research coordinator Janette Alexander for assistance in participant screening, Jonathon Baell from the Walter and Eliza Hall Institute Division of Medicinal Chemistry for synthesis of deuterated capromorelin and staff of the Nucleus Network Clinical Trials Unit, Austin Health. Dr Shinichi Koizumi of Raqualia Pharma Inc. kindly provided in-house data from previous trials of capromorelin in human subjects.
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Ellis, A., Zeglinski, P., Brown, D. et al. Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers. Spinal Cord 53, 103â108 (2015). https://doi.org/10.1038/sc.2014.218
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DOI: https://doi.org/10.1038/sc.2014.218
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