Safety and Tolerability of Concomitant Administration of Multiple-Dose AM833 With Semaglutide 2.4 MG for Weight Management
Bibliographic record
Abstract
Abstract Background: Combining weight management medications with different modes of action may provide more effective treatment options for people with obesity. Subcutaneous (sc) AM833, a long-acting amylin analog, and sc semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, are both under clinical development for weight management. Methods: This was a randomized, double-blind, placebo-controlled, phase 1 trial to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of concomitant administration of six ascending doses of weekly AM833 (0.16, 0.3, 0.6, 1.2, 2.4, or 4.5 mg) + semaglutide vs placebo + semaglutide in subjects with overweight or obesity. The 20-week trial included a 16-week escalation period followed by a 4-week treatment period at target dose and a 5-week follow-up. Eligible subjects were male or female of non-childbearing potential, aged 18–55 years, with BMI 27−39.9 kg/m2. The primary endpoint was number of adverse events (AE) from baseline to follow-up. Secondary endpoints included PK parameters (area under the curve [AUC] 0–168 h [AUC0-168], maximum concentration [Cmax], half-life [t1/2] and time to Cmax [tmax]). Changes in body weight (exploratory endpoint) were analyzed separately for AM833 0.16−2.4 mg + semaglutide (vs pooled placebo) and AM833 4.5 mg + semaglutide (vs matched placebo) due to a different semaglutide dose escalation regimen used in this treatment arm. Results: Of 96 subjects randomized, 95 were exposed to treatment (59% male; mean age 40.6 years, body weight 95.7 kg, BMI 32.1 kg/m2) and 80 (83%) completed the trial. The number of AEs ranged from 37–89 with AM833 (0.16–4.5 mg) + semaglutide and 132 with pooled placebo + semaglutide. Most AEs were mild or moderate and the proportion of subjects with ≥1 AE was similar across treatment arms. About one-third of all AEs were gastrointestinal (GI) disorders (n=207 of 566), primarily nausea, dyspepsia, and vomiting. A greater proportion of subjects reported GI AEs with AM833 1.2–4.5 mg + semaglutide vs placebo + semaglutide. The second most common AEs were injection site reactions (n=72), all mild and not dependent on AM833 dose. Exposure to AM833 was proportional to dose for both AUC0-168 and Cmax, and did not affect semaglutide exposure and elimination. AM833 0.16−4.5 mg t1/2 ranged from 159–195 h and median tmax ranged from 24–72 h. At week 20, body weight changes from baseline with AM833 1.2 and 2.4 mg + semaglutide were greater vs pooled placebo + semaglutide (−15.7% and −17.1% vs −9.8%, respectively; p<0.001) and with AM833 4.5 mg + semaglutide vs matched placebo + semaglutide (−15.4% vs −8.0%; p<0.01). Conclusion: Treatment with AM833 at all tested doses + semaglutide was generally well tolerated with an acceptable safety profile. PK data support once-weekly dosing. The combination of AM833 1.2, 2.4, or 4.5 mg + semaglutide led to greater weight loss compared with placebo + semaglutide.
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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) | 0.000 | 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".