Safety, tolerability, relative bioavailability, pharmacokinetics, and pharmacodynamics of single and multiple doses of the novel oral bofanglutide in healthy Chinese participants.
Oral bofanglutide showed low relative bioavailability and was well tolerated in healthy participants, but further studies are needed to assess its clinical utility.
Where it sits
this study against the rest of the bofanglutide corpusSummary and findings
The study evaluated the safety, relative bioavailability, pharmacokinetics, and pharmacodynamics of oral bofanglutide in healthy Chinese participants. Participants received either single doses of oral bofanglutide (30, 60, or 90 mg) or subcutaneous injection (0.6 mg), and a multiple-dose regimen for 14 days. No serious adverse events were reported.
Abstract
<h4>Aims</h4>To evaluate the safety, relative bioavailability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral bofanglutide (co-formulated with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate [SNAC]) in healthy Chinese participants.<h4>Methods</h4>Part A enrolled 44 participants to receive single doses of oral bofanglutide (30, 60, or 90 mg) or subcutaneous bofanglutide injection (0.6 mg). Part B enrolled 48 participants to receive once-daily oral bofanglutide for 14 days (30 mg then 60 mg), with a post-dose fast of 30 or 60 min.<h4>Results</h4>Most treatment-emergent adverse events (AEs) related to oral bofanglutide were grade 1 gastrointestinal AEs; no serious AEs or severe hypoglycemia occurred. In Part A, single-dose relative bioavailability was 0.56% (30/60 mg) and 1.31% (90 mg). The maximum plasma concentration (C<sub>max</sub>) and area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC<sub>0-t</sub>) increased dose‑dependently from 40.95 to 254.47 ng/mL and from 3980.76 to 28180.67 h·ng/mL. In Part B, a 60‑minute post‑dose fast produced approximately twice the exposure of a 30‑minute fast, with apparent relative bioavailability of 9.22% vs. 4.88% (based on repeated-dose exposure with accumulation).<h4>Conclusions</h4>Oral bofanglutide was safe and well tolerated. The PK/PD profiles support further investigation of once-daily oral bofanglutide for type 2 diabetes and overweight/obesity.
Background
This paper addresses the pharmacokinetics and safety of oral bofanglutide, a novel peptide, in a healthy population. Previous studies have primarily focused on injectable formulations, and there is limited data on the oral bioavailability of bofanglutide. Understanding the pharmacokinetics and safety profile in humans is crucial for evaluating its potential use in managing type 2 diabetes and obesity.
Methods
The study consisted of two parts: Part A included 44 participants receiving single doses of oral bofanglutide (30, 60, or 90 mg) or a subcutaneous injection of 0.6 mg. Part B included 48 participants receiving once-daily oral bofanglutide for 14 days, starting with 30 mg and then increasing to 60 mg, with post-dose fasting periods of 30 or 60 minutes.
Results
In Part A, the relative bioavailability for the 30/60 mg dose was 0.56%, and for the 90 mg dose, it was 1.31%. The maximum plasma concentration (Cmax) increased from 40.95 ng/mL for the lowest dose to 254.47 ng/mL for the highest dose. The area under the concentration-time curve (AUC0-t) increased from 3980.76 h·ng/mL to 28180.67 h·ng/mL with increasing doses. In Part B, the 60-minute post-dose fast resulted in a relative bioavailability of 9.22%, compared to 4.88% for the 30-minute fast.
Interpretation
The findings suggest that oral bofanglutide has a low relative bioavailability, which is consistent with many orally administered peptides. While the pharmacokinetic parameters are statistically significant, the clinical relevance of the observed bioavailability remains uncertain. The study's limitations, including a small sample size and the focus on a specific demographic, may restrict the applicability of the results to broader populations.
Key findings
- Relative bioavailability was 0.56% for 30/60 mg and 1.31% for 90 mg.
- Cmax increased from 40.95 ng/mL to 254.47 ng/mL with increasing doses.
- AUC0-t increased from 3980.76 h·ng/mL to 28180.67 h·ng/mL with increasing doses.
- A 60-minute post-dose fast produced relative bioavailability of 9.22% compared to 4.88% for a 30-minute fast.
Limitations
- small sample size (n=44 for Part A, n=48 for Part B)
- single-site study may limit generalizability
- short follow-up duration
- no serious adverse events reported limits understanding of safety profile