S1370 Single Ascending Dose Results From a Phase 1 Clinical Trial of BT-600, a Combination Product of the NaviCap Targeted Oral Delivery Platform and Tofacitinib
Bibliographic record
Abstract
Introduction: The NaviCap platform uses an oral drug delivery capsule that autonomously identifies locations in the gastrointestinal (GI) tract for anatomically targeted delivery (Figure 1). The device is designed to deliver a liquid drug formulation directly to the colon mucosa, bypassing the upper GI tract. In patients with ulcerative colitis, delivery to the colon could improve efficacy and reduce toxicity with lower systemic drug exposure. Results of device function studies without drug have previously been reported. Here we report interim results of the Phase 1 clinical trial of BT-600, a drug-device combination of NaviCap with a liquid formulation of tofacitinib. Methods: This Phase 1 randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD/MAD) clinical trial evaluated the safety and pharmacokinetics (PK) of BT-600 in healthy adult participants. In Part 1, participants (n=24) received a single dose of BT-600 with tofacitinib 5 mg (n=9), 10 mg (n=9), or placebo (n=6). Part 2 (n=24) will assess safety, plasma, and colonic tissue exposure of BT-600 or placebo daily for 7 days. A pre-specified interim analysis included results on safety, plasma PK, and evidence of drug in feces in Part 1. Results: Adverse events were mild, transient, and consistent with those expected in a healthy population. All 24 participants demonstrated systemic absorption following a single dose, with PK parameters consistent with colonic delivery, in distinction to delivery in the upper GI tract. Tofacitinib was first detected in plasma at ∼6 hours following administration of BT-600. The median time to reach maximum plasma concentration (Tmax) was 8–10 hours vs 0.5–1.0 hours for conventional oral tofacitinib. Colonic delivery of BT-600 was associated with 3–4x lower systemic absorption of tofacitinib vs conventional oral tofacitinib, with plasma tofacitinib Cmax arithmetic mean (SD) values of 26 (14.8) ng/mL for BT-600 at the 10 mg dose (Table 1). Drug was present in fecal samples of all participants. Overall AUCs and peak (Cmax) exposures to plasma tofacitinib increased in a dose proportional manner from BT-600 5 mg to 10 mg. Conclusion: Interim results of the Phase 1 clinical trial in healthy adult participants showed that BT-600 was well tolerated and achieved colonic drug delivery with lower systemic exposure than seen with conventional oral tofacitinib.Figure 1.: The NaviCap device. Table 1. - Plasma tofacitinib pharmacokinetic parameters following administration of a single oral dose of 5 mg or 10 mg BT-600 in healthy participants (PK Population) BT-600 5 mg (n=9) BT-600 10 mg (n=9) Xeljanz 10mg† AUC0-last (ng.hr/mL) 123 (37) 257 (133) 283 (80) AUC0-inf (ng.hr/mL) 128 (35) 266 (132) 289 (81) Cmax (ng/mL) 14 (4.2) 26 (14.8) 88 (10.2) Tmax (hours) 8 (6–16) 10 (6–16) 0.5 (0.25–1.0) t½ (hours) 4.9 (1.59) 7.8 (3.24) 2.61 (0.633) Mean (SD) shown for all parameters, except Tmax, where median and range are shown.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".