Clinical Outcomes, Safety, and Pharmacokinetics of OPT-80 in a Phase 2 Trial with Patients with<i>Clostridium difficile</i>Infection
Bibliographic record
Abstract
OPT-80, a novel, minimally absorbed macrocycle, is a candidate treatment option for Clostridium difficile infection (CDI) based on cure without recurrence of CDI in the hamster challenge model, good in vitro activity against C. difficile, and relative sparing of commensal gram-negative anaerobes. In this open-label, dose-ranging clinical trial, 48 evaluable subjects were randomized to receive either 50, 100, or 200 mg of OPT-80 orally every 12 h for 10 days as treatment for mild to moderately severe CDI. OPT-80 was well tolerated by all subjects. Plasma concentrations were below the lower limit of quantitation in almost one-half of patients and typically <or=20 ng/ml across the dose range; the mean fecal concentrations exceeded the MIC at which 90% of the isolates tested are inhibited by 2,000- to 10,000-fold with increasing dosages. Resolution of diarrhea within 10 days was achieved in 10/14 patients (71%), 12/15 patients (80%), and 15/16 patients (94%), and the median time to resolution of diarrhea was reduced from 5.5 to 3.0 days with increasing dosages. Across all groups, the clinical cure rate, which was defined as resolution of diarrheal disease without the need for further treatment, was 41/45 patients (91%). Recurrence of CDI at approximately 1 month after treatment was observed in two (5%) patients, one each in the 100-mg and 400-mg groups. The apparent high clinical response, good tolerance, low recurrence rate, and more-complete and rapid symptom control with the highest dosage support the selection of the 200-mg twice-daily dose for further clinical development of OPT-80 for treatment of CDI.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| 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".