A total of 26 subjects were randomized in the trial to account for potentially withdrawn subjects. All statistical analyses were performed using SAS versions 9. The analysis of the primary end point was controlled for type 1 error.
Other analyses were not controlled for multiplicity. The planned analysis of the primary end point, anatomical location of the tablet at CTE, could not be performed because CTE occurred in the stomach for all evaluated subjects with both water volumes. Thus, the primary end point was only summarized by descriptive statistics. Safety end points were summarized by descriptive statistics using the safety analysis set comprising all subjects receiving at least 1 dose of trial product.
Subject disposition is provided in Supplemental Figure S1. A total of subjects were screened, 29 were enrolled, 27 were randomized, 26 were exposed to trial product, and 24 completed the trial. All 26 exposed subjects were included in the safety analysis set and in the full analysis set.
For 1 subject, scintigraphic results except esophageal transit time after dosing with mL water were excluded because the scintigraphic imaging was terminated because of an AE of vomiting. Representative scintigraphic images of tablet erosion are shown in Figure 2. CTE occurred in the stomach for all evaluated subjects irrespective of water volume administered with the tablet. The white line shows the stomach outline. The estimated mean time to initial tablet erosion was 2.
The geometric mean esophageal transit time was 1. Individual esophageal transit time ranged from 0. Median t max,semaglutide was 1. Values below LLOQ were set to zero. End points were analyzed on a logarithmic scale but are presented on the linear scale. C max , maximum concentration. Lines represent the simple regression lines for dose administration with 50 and mL of water, respectively.
Note that both horizontal and vertical axes are presented using logarithmic scale. C max , maximum concentration; t max , time to maximum concentration. Median t max,SNAC was 0. A total of 7 events of headache occurred on the day of dosing, whereas 3 events of headache occurred 8, 20, and 22 days after dosing, respectively.
All subjects recovered from the events of headache within 1—2 days. The last event of nausea occurred 2 days after dosing, and the subject recovered within 6 days. No severe or serious AEs were reported during the trial. The majority of AEs were mild 47 events , whereas 7 AEs were moderate these all occurred on the day of dosing and subjects recovered within 1 day, except for an event of hand fracture [broken finger] that occurred 5 days after dosing, and the subject recovered within 16 days.
No severe or confirmed hypoglycemic episodes were reported during the trial, and there were no clinically relevant observations related to vital signs, physical examination, or electrocardiogram. There were no clinically relevant observations in laboratory safety parameters, except temporary asymptomatic increased amylase and lipase levels in 1 subject on the day after first dosing, which had returned to normal levels 5 days later.
The key results were that CTE of oral semaglutide occurred in the stomach irrespective of water volume administered with dosing and that higher systemic semaglutide exposure and longer time to maximum semaglutide plasma concentration both correlated with longer time to CTE.
With an oral semaglutide tablet size of 7. However, this was not observed. The tablet did not pass to the duodenum in intact form in any of the subjects. Nonetheless, the observed correlations between longer time to complete gastric emptying and greater semaglutide exposure may lead to the interpretation that the longer the tablet remains in the stomach, the higher the systemic exposure of semaglutide.
This is in line with conclusions drawn based on recent animal data, including the finding that prevention of intestinal absorption by pyloric ligation in dogs did not result in decreased semaglutide plasma exposure compared with that seen in nonligated dogs after administration of oral semaglutide. Still, it may be speculated if slower tablet erosion could lead to a more optimal rate of release of semaglutide and SNAC molecules from the tablet to facilitate semaglutide absorption. This hypothesis is also supported by the current finding of a correlation between slower tablet erosion and longer time to maximum semaglutide plasma concentration.
Another study showed that the presence of food in the stomach substantially limited the absorption of oral semaglutide. This apparent discrepancy may be explained by the findings of the present study. The lower SNAC absorption when oral semaglutide was administered with 50 mL water raises the possibility that at least to a certain extent, higher availability of SNAC remaining in the stomach for a longer period may facilitate semaglutide absorption.
The current study showed a similar esophageal transit time of 1. Thus, even when the oral semaglutide tablet was administered with as little as 50 mL water, the tablet passed freely and rapidly through the esophagus. Still, to improve patient convenience, it would be desirable to allow for more than 50 mL water to be taken with the oral semaglutide tablet. It is therefore reassuring that a recent study assessing semaglutide exposure after different dosing conditions demonstrated no difference in semaglutide exposure between water volumes of 50 and mL administered with the tablet.
The relatively high frequency of headache can most likely be ascribed to the prolonged fasting and the many experimental procedures performed. The frequency of reported gastrointestinal AEs should be viewed in light of the single dose of 10 mg oral semaglutide administered.
However, it is important to bear in mind that given the peptide character of semaglutide, any molecules released from the tablet are exposed to rapid enzymatic degradation if not readily absorbed. A strength of the present study was the use of scintigraphic imaging to follow the movement of the oral semaglutide tablet through the gastrointestinal tract in a fully noninvasive manner.
Scintigraphy is considered the gold standard to investigate the disintegration and dissolution process of a solid oral dosage form in humans. Scintigraphy allows subjects to be in a standing or sitting position during measurements, which is in contrast with, for example, magnetic marker monitoring, in which the stationary sensoring systems necessitate a restrictive setup with subjects in a supine position.
If you are interested in the SNAC 2 trial ask your breast surgeon if it is suitable for you. We support, inform and represent those with breast cancer so they can make informed choices about their treatment and care. Formed in , BCAC is a registered charity run by breast cancer survivors. If you would like to join us to help improve breast cancer treatment and care in Aotearoa, New Zealand please email us to find out more.
You are here Home » Sentinel node biopsy versus axillary clearance biopsy clinical trial. Sentinel node biopsy versus axillary clearance biopsy clinical trial SNAC-2 is a trial comparing two operations for detecting cancer cells in the lymph nodes of women with early breast cancer.
The two operations are: axillary clearance sentinel node biopsy. Intervention assignment. Parallel Query! Other design features. Phase 3 Query! Type of endpoint s. Recruitment status. Active, not recruiting Query! Date of first participant enrolment. Date of last participant enrolment. Date of last data collection. Sample size. Recruitment in Australia. Recruitment state s. Recruitment outside Australia.
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Brief summary. The Sentinel Node versus Axillary Clearance SNAC trial was the first, large, Australasian prospective assessment of the risk of lymphoedema after surgery for early breast cancer. The trial compared sentinel node biopsy of selected lymph nodes with clearance of axillary nodes in women with tumours smaller than 3 cm.
Short-term results showed that arm swelling was less in the group having only sentinel node biopsy. Both treatment groups had moderate limitations in arm movement over the first 6 months, which then recovered to near normal levels. The results showed that for women with small tumours, sentinel node biopsy was a viable alternative to axillary clearance.
The patients are being followed up so that long-term effects can be measured.
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