A Phase 1C, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DM199 Administered Intravenously with a Polyvinyl Chloride Bag in Adult Healthy Subjects and Adults Recently Taking Angiotensin‐Converting Enzyme Inhibitors
Bibliographic record
Abstract
This small phase 1C, open-label, single ascending dose study evaluated the safety, tolerability, and pharmacokinetics (PKs) of DM199, a recombinant form of human tissue kallikrein-1 (KLK1). A small sample size of both healthy subjects and hypertensive adults recently taking angiotensin-converting enzyme inhibitors was studied. KLK1 has a known role in vasodilation and blood flow regulation, with potential implications for treatment of acute ischemic stroke (AIS) by focally enhancing cerebral perfusion. A total of 12 subjects were enrolled; 9 healthy subjects received escalating doses of DM199 (0.1-0.5 µg/kg), while 3 hypertensive subjects received the maximum tolerated dose of 0.5 µg/kg. Safety assessments indicated that DM199 was well tolerated, with mild adverse events reported, such as headache and flushing. No infusion-related hypotensive events occurred, and all subjects completed the study without significant clinical issues. The study was performed following prior PK analyses revealing that DM199 exposure was greater when administered with polyvinyl chloride infusion materials compared with polyolefin infusion materials. This study supports a revised dosing strategy for DM199 in the ongoing ReMEDy2 trial for AIS and highlights the need for careful consideration of the risk-benefit profile in the clinical context of AIS treatment.
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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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".