Use of the Nutromics Sensor Device for the determination of Vancomycin concentrations and to evaluate biosensor safety.

The Nutromics Biosensor collects raw electrochemical data through DNA sensor on minimally invasive needles piercing the skin (~1mm) for the continuous monitoring and quantitative estimation of the drug Vancomycin concentrations in ISF. Stage 1 • Review of medical condition and any changes in medications. • Pregnancy test (blood) - for female participants with childbearing potential only. • A sensor will be placed onto the participant’s upper arm. The time of sensor application will be recorded. After the sensor has been applied for 8 h (±15 min), the sensor will be removed. • Blood samples for relevant pathology tests will be collected 10 to 30 minutes before sensor application, at 4 h (±15 min) post-application and 10 to 30 minutes post-removal of the sensor. • Digitally captured images/recordings of the skin surface at the sensor application site; before and after the application and removal of the sensor to assess any skin irritation. Care will be taken to avoid capturing identifiable features of the participant. • Participants will be required to complete a pain scale survey 5-10 minutes post-application and 5-10 minutes after removal of the sensor • Participants will be required to conduct a physical challenge post-application of the sensor. • 5-10 minutes prior to removal of the sensor, a mobility survey will be completed • Participants will be monitored throughout the study duration for any adverse events. Participants will be observed for at least 15 minutes post removal of the sensors. Stage 3a • Participants will be asked to attend the study site and the following procedures will be conducted: • Review of medical condition and any changes in medications. • Pregnancy test (blood) - for female participants with childbearing potential only. • An intravenous cannula will be inserted in both left and right arms. One cannula will be used for administering intravenous vancomycin and the other cannula is for blood sample collection. • A sensor will be placed onto the participant’s upper arm opposite the arm where the vancomycin is being infused. The time of sensor application will be recorded. Sensor application will be 30 minutes (+15 min) prior to administering the vancomycin infusion and the sensor will be removed 10 h (±15 min) post-cessation of the infusion. • Blood samples for relevant pathology tests (FBC, UEC and LFT) will be collected (10 to 30 minutes prior to application of the sensor and 10 to 30 minutes post-removal of the sensor. If the participant consented to providing blood samples for future research, these are to be collected prior to the placement of the sensor, or once the sensor has been removed, at the time most convenient for the Clinical Team. • 30 minutes (+15 min) post-application of the sensor, the participant will receive a single dose of vancomycin as an intravenous infusion (1 gram over 1 hour 40 minutes). The time of administration and completion of infusion will be recorded. • Blood samples for the measurement of vancomycin concentrations will be collected prior to the administration of vancomycin infusion, 30 min (±5 min) and 1 h (±10 min) during the infusion, at the end of the infusion (+15 min) and then at 40 min (±15 min), 1.5 h (±15 min), 2 h (±15 min), 3 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min) and 10 h (±15 min) after the infusion has been completed. • Participants will be required to complete a pain scale survey 5-10 minutes post-application and 5-10 minutes after removal of the sensor • Participants will be required to conduct a physical challenge post-application of the sensor. • 5-10 minutes prior to removal of the sensor, a mobility survey will be completed. • Digitally captured images/recordings of the skin surface at the sensor application site, before and after application and removal of the sensor, will be taken to assess any skin irritation. Care will be taken to avoid capturing identifiable features of the participant. • Participants will be monitored throughout the study duration for any adverse events. Given the duration of this Study Visit, participants will be required to stay overnight. In the absence of any adverse events, participants will be discharged from the following morning after being observed for at least 15 minutes post removal of the sensors. Stage 3b • An intravenous cannula will be inserted in both left and right arms. One cannula will be used for administering intravenous vancomycin (n=3 participants with the cannula in their left arm and n=3 participants with the cannula in their right arm) and the cannula in the opposite arm is for blood sample collection. - The first sensor will be applied onto one of the participant’s upper arms. Sensor will be applied 30 minutes (+15 min) prior to administering the first vancomycin infusion and removed up to 10 h post-cessation of the second vancomycin infusion (all sensors will be removed up to 24 hours after the application of the first pair of sensors) - Blood samples for relevant pathology tests (FBC, UEC and LFT) will be collected 10 to 30 minutes prior to application of each sensor. - If the participant consented to providing blood samples for future research, these are to be collected prior to the placement of the sensor, or once the sensor has been removed - 30 minutes (+15 min) post-application of the sensor, the participant will receive two intravenous vancomycin doses (each dose 1 gram) administered 12 hours apart (start to start). Each intravenous vancomycin dose will be infused over 1 hour 40 minutes. The time of administration and completion of each infusion will be recorded. - Blood samples for the measurement of vancomycin concentrations will be collected before the administration of the first vancomycin infusion, 30 min (±5 min) and 1 h (±10 min) during the infusion, at the end of the infusion (+15 min) and then at 40 min (±15 min), 1.5 h (±15 min), 2 h (±15 min), 3 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min) and, 10 h (±15 min) after the infusion has been completed. - A second sensor will be placed 10 h (±15 min) after the beginning of the first vancomycin infusion The additional sensor will be placed on to the other participants’ upper arm (such that there is one Nutromics Sensor Device on each of the partcipants upper arms). The sensor that was originally placed on the participant’s upper arm will also remain applied - Blood samples for relevant pathology tests (FBC, UEC and LFT) will be collected 10 to 30 minutes post-removal of both the first and second sensors. - Blood samples for the measurement of vancomycin concentrations will be collected 5-10 minutes before commencing the second vancomycin infusion, at 30 min (±5 min) and 1 h (±10 min) during the infusion, as well as at the end of the infusion (+15 min) and then at 40 min (±15 min), 1.5 h (±15 min), 2 h (±15 min), 3 h (±15 min), 4 h (±15 min), 6 h (±15 min) and 8 h (±15 min) after the infusion has been completed. - Participants will be required to complete a pain scale survey 5-10 minutes post-application of each sensor and 5-10 minutes after removal of the sensor - Participants will be required to conduct a physical challenge post-application of each sensor. - 5-10 minutes before the second Nutromics Sensor Device is applied, and 5-10 minutes prior to removal both sensors, a mobility survey will be completed. - Digitally captured images/recordings of the skin surface at the sensor application site after removal of each sensor Stage 3c - An intravenous cannula will be inserted in both left and right arms. One cannula will be used for administering intravenous and the cannula in the opposite arm is for blood sample collection. - Blood samples for relevant pathology tests be collected 10 to 30 minutes prior to application of the sensor will and 10 to 30 minutes post-removal of the sensor - Pregnancy test (blood) – for female participants with child bearing potential only. - Four Nutromics Sensor Devices will be applied; two will be placed on the upper arm of the participant (same arm), one will be placed on the abdomen and the fourth will be applied to either of the participant’s lower leg. A fifth Nutromics Sensor Device will be applied to the opposite forearm 12 hours after the first set of devices were applied. - All sensors will remove up to 24 hours after the application of the first set of sensors - The participant will receive two vancomycin doses (each dose: 700 mg) administered intravenously. Each Vancomycin dose will commence 1 hour and 30 minutes following the application each set of Nutromics Sensor Devices. The vancomycin infusions will be administered 12 hours apart (start-to-start). Each intravenous vancomycin dose will be infused over 1 hour 10 minutes. - Blood samples will be collected prior to the administration of the first vancomycin infusion, 30 min (±5 min) during the infusion, at the end of the infusion (+15 min), and then at 40 min (±15 min), 1.5 h (±15 min), 2 h (±15 min), 3 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min) and 10 h (±15 min) after the infusion has been completed. - Blood samples will be collected at 30 min (±5 min) during the infusion, the end of the second vancomycin infusion (+15 min) and then at 40 min (±15 min), 1.5 h (±15 min), 2 h (±15 min), 3 h (±15 min), 4 h (±15 min), 6 h (±15 min), and 8 h (±15 min) after the infusion has been completed. - Before and after the application and removal of the sensor, photographs/recordings of the skin surface at the sensor application site - Participants will be required to complete a pain scale survey 5-10 minutes post-application of each set of sensors and 5-10 minutes after removal of all the sensors - Participants will be required to conduct a physical challenge post-placement of each set of sensors. - 5-10 minutes prior to removal of the sensors, a mobility survey will be completed