| Popis: |
A double-blind, randomised, single-dose parallel group study was performed to compare the tolerability, pharmacokinetics and pharmacodynamics of MTD201 30 mg octreotide (test product) and Sandostatin LAR 30 mg (reference product) in healthy subjects. MTD201 uses Q-Sphera™ printing technology to precisely control microparticle size, which facilitates simpler reconstitution and injection using smaller needle size than Sandostatin LAR (SLAR) or Somatuline Autogel. MTD201 is being developed for acromegaly and NETs as an alternative to these existing long-acting treatments. Methods: 24 male and female healthy subjects were randomised to receive a single, 30mg i.m. injection of MTD201 (N=12) using a 21G needle or Sandostatin LAR (N=12) using the pre-packed 19G needle. Plasma samples for determination of octreotide, growth hormone (GH) and IGF-1 concentrations were obtained throughout the 63-day period after injection. The plasma GH response to a GHRH+arginine challenge, an accepted surrogate efficacy endpoint for somatostatin analogues, was performed 7 days before octreotide dosing and repeated 28- and 45-days post-dose. Additional data were collected to check for presence of anti-octreotide antibodies and injection site reactions were scored regularly for 7 days post-injection. Results: Both treatments were well tolerated, with AEs consistent with octreotide treatment. Overall plasma octreotide exposures for the test and reference drugs were comparable whilst subjects receiving MTD201 illustrated lower initial spike in plasma octreotide (burst; 0.12ng/mL and 0.99ng/mL for MTD201 and SLAR, respectively), a more linear, consistent profile, and lower variability across the intended dose interval (28 days). Both treatment groups showed detectable plasma octreotide levels up to the final PK sampling point of 63 days. GH and IGF-1 suppression were highly comparable across treatments, with ≈25% and ≈30% reductions from baseline for both groups, respectively. Injection site reactions were less frequent and of lower severity in subjects who received MTD201. Specifically, pain at the injection site was observed in 8% (MTD201) and 25% (SLAR) of subjects, and injection site tenderness in 8% (MTD201) and 83% (SLAR) of subjects. Conclusions: MTD201 produced a safe and effective sustained-release profile of octreotide, supporting a once-monthly treatment interval, as is indicated for SLAR. Therapeutic octreotide concentrations and GH/IGF-1 suppression comparable with SLAR were achieved. Combined with the other advantages for MTD201 regarding smaller needle size, simpler and more reliable reconstitution and injection, these results warrant further study in a suitably powered clinical trial to formally establish MTD201 as an alternative long-acting somatostatin analogue product. |
