0. ALDOXORUBICIN-P3-STS-01 Aldoxorubicin Clinical Reconstitution Procedure

1. Introduction
The following procedure is for the reconstitution of aldoxorubicin drug product for use in the ALDOXORUBICIN-P3-STS-01 study.
The reconstitution should be performed at room temperature.
The total time allotted for reconstitution and patient infusion is not to exceed 120 minutes.
This procedure requires that an initial volume is removed from the IV infusion bag prior to the injection of the reconstituted drug product.
Required Materials:
1x 60 mL syringe (to remove Lactated Ringers solution)
2x 20 mL syringe (to transfer diluent and drug product)
1x timer (to record total time from reconstitution to infusion completion)

2. Steps 1-2
Step 1. Calculate patient Body Surface Area (BSA). Step 2. See Table 1 to determine the number of drug product vials and diluent vials required for reconstitution in order to deliver the targeted dose based on the patient’s BSA. Each lyophilized drug product vial requires one vial of diluent. Remove vials from -20˚C freezer and allow to equilibrate to room temperature for 20 minutes prior to reconstitution. Example: A 350 mg/m2 dose for a patient with a BSA of 1.5 requires 3 vials per cycle. This will require 3 vials of lyophilized drug product and 3 vials of diluent.

3. Step 3
Step 3: From the 250 mL Lactated Ringer’s IV infusion bag remove the volume of solution indicated in Table 1 for the respective dose and discard. Set the IV bag aside once the appropriate volume has been removed. Example: A 350 mg/m2 dose for a patient with a BSA of 1.5 requires 53 mL of reconstituted aldoxorubicin be injected into a 250 mL Lactated Ringer’s IV bag. According to Table 1; 53 mL must first be removed from the IV bag prior to injecting the reconstituted aldoxorubicin for a final infusion volume of 250 mL, yielding a final concentration of 2.1 mg/mL.
Prepare the IV Bag

4. Reconstituting the Drug Product
Step 4
Reconstituting the Drug Product
Step 4: Remove 20 mL of aldoxorubicin diluent from the diluent vial using a syringe. Transfer the diluent into the vial of dried aldoxorubicin drug product. Each lyophilized vial of aldoxorubicin (200 mg) requires 20 mL of diluent for reconstitution for a final concentration of 10.0 mg/mL.

5. Step 5
Step 5: Gently swirl the vial of drug product and diluent to obtain a homogeneous mixture. Inspect the reconstituted solution of drug product to assure the drug is completely dissolved and there is no foreign matter present. Record time at start of reconstitution. Total time from the start of reconstitution to the end of infusion must be less than 120 minutes.

6. Steps 6-7
Step 6: Withdraw the required volume of reconstituted solution (according to Table 1) from the vials and transfer the solution into the IV infusion bag using a suitably sized syringe. Step 7: Gently mix the contents of the IV infusion solution completely to obtain a homogeneous mixture.

7. Steps 8-10
Step 8: Store the IV infusion solution at room temperature. Step 9: Begin patient infusion. Infusion must be completed no more than 120 minutes from the start of reconstitution procedure. Step 10: Retain all vials until the next monitoring visit.

8. Table 1. ALDOXORUBICIN-P3-STS-01 RECONSTITUTION GUIDE
Total Dose (mg)
# of Aldoxorubicin Vials Per Cycle/# of Diluent Vials Per Cycle
Volume of Aldoxorubicin for IV Bag Injection (mL)
 Lactated Ringer's
IV Bag (mL)
 Volume to Remove from IV Bag (mL)
Final Infusion
Volume (mL)
200
2/2 20
250
220 22
240 24
260 26
280 28
300 30
320 32
340 34
360 36
380 38
400
3/3 40
420 42
440 44
460 46
480 48
500 50
520 52
540 54
560 56
580 58
600
4/4 60
620 62

9. Table 1. ALDOXORUBICIN-P3-STS-01 RECONSTITUTION GUIDE
Total Dose (mg)
# of Aldoxorubicin Vials Per Cycle/# of Diluent Vials Per Cycle
Volume of Aldoxorubicin for IV Bag Injection (mL)
 Lactated Ringer's
IV Bag (mL)
 Volume to Remove from IV Bag (mL)
Final Infusion
Volume (mL)
640
4/4 64
250
660 66
680 68
700 70
720 72
740 74
760 76
780 78
800
5/5 80
820 82
840 84
860 86
880 88
900 90
920 92
940 94
960 96
980 98
1000
6/6
100
1020
102
1040
104