Somnolence and Sedation Were Transient Adverse Events for Most Patients Receiving Clobazam Therapy: Post Hoc Analysis of Trial OV-1012 Data
Bibliographic record
Abstract
Background: Somnolence-related adverse events (AEs) are common with benzodiazepine treatment. Clobazam is a uniquely structured 1,5-benzodiazepine indicated in the US for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥ 2 years old. This post hoc analysis of the phase III OV-1012 trial evaluated the incidence, as well as time to onset and resolution, of somnolence and/or sedation AEs following treatment with clobazam for patients with LGS. Methods: OV-1012 was a double-blind, placebo-controlled study that compared three oral dosages of clobazam with placebo as adjunctive therapy in patients 2 - 60 years of age with LGS. Following a 4-week baseline phase, patients who had ≥ 2 drop seizures per week were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day (low-dosage, medium-dosage, and high-dosage, respectively). Treatment included a 3-week titration phase, followed by a 12-week maintenance phase. Incidence, time to onset, duration, and time to resolution of somnolence/sedation AEs were analyzed for patients treated with placebo, or low-, medium-, or high-dosage clobazam. Results: The incidence of somnolence and/or sedation was greater for patients treated with any dosage of clobazam (26%) than placebo (15%), and the incidence increased with greater dosages of clobazam (low-dosage, 17%; medium-dosage, 27%; and high-dosage, 32%). For most patients, onset of these events was within the first 3 weeks of treatment, corresponding to the titration phase. The majority of these events resolved (placebo, 73%; low-dosage, 82%; medium-dosage, 63%; and high-dosage, 83%). The median duration of these somnolence/sedation AEs was 1 month for all clobazam treatment groups. Conclusions: Somnolence and sedation were relatively common AEs observed during clobazam treatment for LGS in OV-1012 and were dosage-related. Most of these events were transient and resolved within a few weeks. J Neurol Res. 2015;5(4-5):252-256 doi: http://dx.doi.org/10.14740/jnr334w
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.014 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.007 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".