Pharmacokinetic Comparability and Safety Between Original and Citrate-Free Mirikizumab Formulations for Subcutaneous Injections: Results from Three Clinical Trials
Bibliographic record
Abstract
Mirikizumab, a p19-directed antibody against interleukin-23 (IL-23), is administered by subcutaneous (SC) injection. Injection site pain (ISP) associated with citrate buffers may negatively affect patient adherence to SC-administered treatments. We assessed the bioequivalence and safety of the citrate-free (CF) and original formulations of mirikizumab. The formulations were assessed in three phase 1, two-arm, randomized, single-dose, parallel design studies in healthy participants: study A (NCT04548219), study B (NCT05515601), and study C (NCT05644353). Participants were randomized 1:1 to either formulation, then further randomized to injection site locations of abdomen, arm, or thigh. The relative bioavailability (RBA) study A had a primary objective of assessing the RBA of a single 200 mg dose. Bioequivalence (BE) studies B and C had the primary objective of assessing the BE of a 200 and 300 mg dose, respectively. In all studies, the primary endpoints were C max , AUC(0–∞), and AUC(0– t last ). The secondary objective was to assess safety and tolerability by treatment-emergent adverse events and serious adverse events. In study A, ISP was quantified prospectively using the 100-mm validated visual analogue scale (VAS) assessment form. The primary objective was met in all studies. The RBA study found no significant difference in exposure between the formulations. BE was demonstrated between CF and original mirikizumab in both BE studies, with the 90% confidence intervals of the ratios of geometric least squares means within the pre-specified equivalence limits of 0.80 and 1.25. The frequency of ISP and injection site reactions (ISRs) was lower for CF than original mirikizumab in all studies. Furthermore, a significant difference in mean VAS score was observed in study A. Mirikizumab CF and original formulations were bioequivalent. The CF formulation was associated with less pain and fewer ISRs, with no other notable differences in safety profiles. ClinicalTrials.gov identifier NCT04548219, NCT05515601, NCT05644353.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".