A Pooled Analysis of the Safety and Efficacy Results of the Multicenter, Double-Blind, Randomized, Placebo-Controlled Phase 3 REFINE-1 and REFINE-2 Trials of ATX-101, a Submental Contouring Injectable Drug for the Reduction of Submental Fat
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: ATX-101, a proprietary, synthetic version of naturally-occurring deoxycholic acid, is an investigational injectable drug under development for the reduction of excess submental fat (SMF). ATX-101 causes focal adipocytolysis when injected into subcutaneous fat. STUDY DESIGN AND PURPOSE: Two independent, identical, multicenter (US/Canada), randomized, double-blind, placebo-controlled phase 3 studies (REFINE-1 and REFINE-2) were conducted to evaluate the safety and efficacy of ATX-101. The pooled analysis from these two studies is presented here. METHODS: Patients (N=1022; 1019 treated with ATX-101 or placebo) with moderate-to-severe SMF, as rated by clinicians and patients, were randomized (1:1) to receive subcutaneous injections of ATX-101 (2 mg/cm2) or placebo into the SMF for up to 6 treatment sessions, approximately 28 days apart. Primary endpoints were changed from pre-treatment to 12 weeks post-treatment in (1) percentage of patients with a ≥1-grade change in the Clinician-Reported (CR) and Patient-Reported (PR) Submental Fat Rating Scales (SMFRS) composite and (2) percentage of patients with a ≥2-grade change in the CR-SMFRS/PR-SMFRS composite. Secondary endpoints were (1) mean change from baseline in the PR Submental Fat Impact Scale (PR-SMFIS) and (2) reduction in SMF volume by magnetic resonance imaging (MRI) in a subset of 449 patients. Adverse events (AEs) were monitored throughout. RESULTS: ATX-101 resulted in statistically significant reductions in SMF. The percentage of patients with a ≥1-grade change in the CR-SMFRS/PR-SMFRS composite was 68.2% for ATX-101 vs. 20.5% for placebo (p<.001). The percentage of patients with a ≥2-grade change in the CR-SMFRS/PR-SMFRS composite was 16.0% for ATX-101 vs. 1.5% for placebo (p<.001). ATX-101 treatment decreased the PR-SMFIS total score from baseline (7.3) compared with placebo (7.3; 3.7 vs. 1.3; p<.001) and increased the percentage of patients attaining a pre-specified reduction in SM volume by MRI (ATX-101 vs. placebo: 43.3% vs. 5.3%; p<.001). Most AEs were transient, mild or moderate in severity, and associated with the treatment area. The most common AEs were pain, swelling/edema, hematoma (bruising), anesthesia (numbness), all of which were expected as a result of the pharmacologic action of the drug. Only 1.4% of patients discontinued the studies due to AEs. CONCLUSION: The pooled analysis of the REFINE-1 and REFINE-2 phase 3 trials supports the efficacy and acceptable safety profile of ATX-101, a potential first-in-class injectable drug for contouring the submental region (Table 1).Table 1: Pooled analysis from REFINE-1 and REFINE-2 pivotal phase 3 trials of ATX-101 vs. placebo.CR-SMFRS, Clinician-Reported Submental Fat Rating Scale; PR-SMFS, Patient Reported Submental Fat Rating Scales; PR-SMFIS, Patient-Reported Submental Fat Impact Scale; SMF, submental fat; MRI, magnetic resonance imaging
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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 | 0.009 | 0.016 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it