RANDOMIZED ACTIVE AND PLACEBO-CONTROLLED ENDOSCOPY STUDY EVALUATING A NOVEL PROTECTED FORMULATION OF ORAL ALENDRONATE
Bibliographic record
Abstract
Purpose: Despite good tolerability in clinical efficacy trials, post-marketing surveillance has associated oral aminobisphosphonates with esophageal injury leading to ulceration, stricture or perforation attributed to prolonged pill contact. We undertook a randomized, active and placebo controlled endoscopy study to assess upper gastrointestinal injury with a novel formulation of alendronate (“protected alendronate”), designed to reduce direct contact between the active drug and the upper gastrointestinal mucosa. Methods: Eighty healthy subjects with normal baseline endoscopy were randomly assigned to receive: protected alendronate 70 mg (N = 30); Fos-amax™ 70 mg (N = 30); or (3) a lactose placebo indistinguishable from protected alendronate (N = 20) once daily for 14 days. Endoscopy was repeated on Day 8 and Day 15. Gastric and duodenal injury was rated using Lanza scores and esophageal injury was scored using the Hetzel-Dent scale. Differences in injury scores among treatment groups were assessed by analysis of variance (ANOVA) with post hoc Bonferroni tests. Differences in ulcer rates between groups were assessed using chi square test with post hoc Z tests for pair-wise comparison. Results: Two subjects randomized to Fosamax™ were withdrawn due to protocol violation. The remaining 78 subjects (mean age 48.3 yrs +/- 5.9; 81% female) completed the protocol. Both Fosamax™ and protected alendronate were associated with significantly higher mean gastric Lanza scores than placebo. Mean gastric Lanza scores did not differ significantly between the Fosamax™ and protected alendronate arms. However, severe gastric injury (Lanza score 3 or 4) was more common on Fosamax™ vs. protected alendronate (67.9% vs. 33.3%; p <0.01), and subjects on Fosamax™ were more likely than those on protected alendronate to develop gastric ulcers (21.4% vs. 3.3%; p = 0.03). No ulcers developed among subjects randomized to placebo. No significant differences in duodenal and esophageal injury were observed. Conclusions: Overall gastric Lanza scores did not differ significantly between Fosamax™ and protected alendronate. However, protected alendronate was associated with fewer cases of severe erosive gastritis and fewer gastric ulcers than Fosamax™ when given at an equivalent oral dose. These results suggest that a protected formulation of alendronate reduces its potential for significant upper gastrointestinal mucosal injury.
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 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".