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
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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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 | 0.021 | 0.025 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.015 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".