Scintigraphic evaluation of buspirone hydrochloride time released tablets
Research type
Research Study
Full title
An exploratory, single-centre, open-label, crossover study in healthy volunteers using scintigraphy to evaluate the absorption of buspirone\nhydrochloride from timed-release tablets.
IRAS ID
1004837
Contact name
Holly Mitzel
Contact email
Sponsor organisation
Cingulate Therapeutics
Eudract number
2021-006396-42
Research summary
Research Summary\n\nThis study is to investigate the absorption of buspirone after different lag periods to understand how absorption of the molecule differs at different locations within the GI tract and to use this information to inform the appropriate doses for a triple pulse buspirone formulation.\n\nThe following treatments will be dosed as part of this study\nTreatment A: One timed-release tablet releasing 10 mg buspirone HCl after a 4 hour delay\nTreatment B: One timed-release tablet releasing 10 mg buspirone HCl after an 8 hour delay\nTreatment C: One triple-pulse tablet releasing 10 mg of buspirone HCl at 0, 4, and 8 hours (30mg total)\nTreatment D: One reference tablet containing 10mg buspirone HCl (at Hour 0) (Reference Product)\n\nThe primary purpose of this study is to evaluate the absorption of Buspirone and the presence of the metabolite 1-PP in blood plasma from time-delayed formulations and correlate with scintigraphic time and site of release.\n\nThis study will be conducted in healthy male volunteers aged between 18 - 60 years old. There are not benefits to the subject for participating in the study.\n\nIn this study we will use scintigraphic imaging to confirm the site of release of the tablets in the gastrointestinal tract. To look at this parameter, we will add a small amount of radioactive materials to each tablet. Blood samples will also be taken at specific timepoints throughout each visit to asses the absorption of buspirone in the blood.\n\nSubjects will attend the unit fasted and standardised meals will be provided at set times during the assessment visits. Subjects will be required to attend the study unit on up to six occasions.\n\nSummary of Results\nThis study was an exploratory single centre, open label, crossover study in healthy volunteers using scintigraphy to evaluate the absorption of buspirone hydrochloride from timed-release tablets.\nTwelve healthy male volunteers aged 18-60 years, inclusive, with a Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive, and free from any significant diseases including cardiac, renal and gastrointestinal disease were entered into the study. The first participant was enrolled on 10May2022 and the last participant completed on 17Jun2022. Of the twelve participant enrolled 10 participants completed the study.\nThe primary objective of this study was to evaluate the absorption of buspirone and the presence of the metabolite 1- pyrimidinylpiperazine (1-PP) in blood plasma from time-delayed formulations and correlate with scintigraphic time and site of release.\nNo SAEs were reported in this study. Of the 12 subjects treated, six subjects experienced at least one AE. In total, 10 TEAEs were reported, nine of mild intensity and one of moderate intensity. Three were considered possibly related to the study drug.\nThe TEAEs reported are not unexpected for a group of healthy volunteers. No CS changes in vital signs (blood pressure and heart rate), ECG or physical examination were observed at any of the AV timepoints following treatment. The buspirone HCl timed-release tablets were well tolerated by healthy volunteers, with few TEAEs reported overall and no SAEs.\nThe pharmacoscintigraphic parameters of the time delayed buspirone treatments administered in this study were successfully evaluated and correlated in healthy volunteers, in comparison with the commercially available comparator, with the time delayed Treatments achieving delayed release of the buspirone core(s).\nDelayed release treatments resulted in greatly increased plasma bioavailability of buspirone when compared to the commercial immediate release tablet, however in contrast, plasma levels of the metabolite 1-PP were observed to be highest for immediate release treatment.\nIn the majority of subjects, triple pulse tablets successfully produced three distinct peaks in the buspirone plasma profile, demonstrating as a proof of concept the feasibility for this approach in generating a profile suitable for once-a-day administration.
REC name
London - Westminster Research Ethics Committee
REC reference
22/LO/0136
Date of REC Opinion
18 Mar 2022
REC opinion
Further Information Favourable Opinion