Track: Clinical Pharmacology - Biomolecular - Clinical Trials - Other
Category: Poster Abstract
Dulaglutide 4.5 mg Administered as a Single Dose Pen Achieved Comparable Relative Bioavailability to Prefilled Syringe Administration in Healthy Subjects
Purpose: Once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA), dulaglutide, is approved for the treatment of type 2 diabetes at 0.75 mg and 1.5 mg doses administered by single dose pen (SDP). Investigational dulaglutide doses of 3.0 and 4.5 mg were studied in Phase 2 in a prefilled syringe (PFS). This study evaluated the relative bioavailability and tolerability of a single dose of dulaglutide 4.5 mg administered subcutaneously (s.c.) to healthy subjects as a single injection by SDP (test) compared to 3 injections by PFS (reference). Methods: This was a Phase 1, single-center, open-label, randomized, 2-period, crossover study in healthy subjects. Subjects were randomized in a 1:1 ratio to receive dulaglutide 4.5 mg as a single injection by SDP or as 3 injections by PFS in Period 1 and then switch to the opposite treatment in Period 2 following a washout period of at least 28 days between doses. In each treatment period, subjects were admitted to the clinical research unit (CRU) on Day -1. On the morning of Day 1, after an overnight fast of approximately 8 hours, subjects received a single s.c. dose of dulaglutide according to their assigned treatment sequence. Blood samples were collected pre-dose and up to 336 hours post-dose to measure plasma dulaglutide concentrations. Adverse events (AEs), injection site reactions (ISRs), clinical laboratory tests, vital signs, electrocardiograms, and clinical laboratory tests were assessed. Results: A total of 27 healthy subjects participated in this study (mean±standard deviation baseline characteristics: age 41.7±10.5 years, body mass index 30.6±3.9 kg/m2, 44.4% female). Exposure to dulaglutide based on area under the curve (AUC) and maximum observed concentration, Cmax was similar for SDP and PFS (Figure). The differences in AUC(0-∞), AUC(0-168 h), or Cmax between the two formulations were not clinically relevant, as determined by the 90% CIs for the ratios of geometric least square (LS) means, which spanned unity for all parameters, including Cmax where the 90% CI did not fall between 0.8 and 1.25 (Table). In addition, the median time of maximum observed concentration (tmax) was similar between the two formulations, with no difference because 90% CI spanned unity. Single 4.5-mg doses of dulaglutide administered via SDP and PFS were well tolerated. The most common AEs were gastrointestinal events (nausea and vomiting). Six (23.1%) subjects reported ISRs overall. Mild pain was the most frequently reported ISR. No erythema or edema was reported for any subject. Conclusion: Overall, there was no notable difference in relative bioavailability of a 4.5 mg dose of dulaglutide administered as SDP (test) compared to PFS (reference) and no clinically significant adverse events were observed over the duration of the study. Results from this study supported the use of the SDP and its formulation in Phase 3 clinical development.