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

ALDOXORUBICIN-P3-STS-01Aldoxorubicin Clinical Reconstitution Procedure

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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)

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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.

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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

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Step 4

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.

Reconstituting the Drug Product

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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.

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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.

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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.

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Table 1. ALDOXORUBICIN-P3-STS-01RECONSTITUTION 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 InfusionVolume (mL)

200 2/2 20 250 20 250220 2/2 22 250 22 250240 2/2 24 250 24 250260 2/2 26 250 26 250280 2/2 28 250 28 250300 2/2 30 250 30 250320 2/2 32 250 32 250

340 2/2 34 250 34 250

360 2/2 36 250 36 250

380 2/2 38 250 38 250

400 3/3 40 250 40 250

420 3/3 42 250 42 250

440 3/3 44 250 44 250

460 3/3 46 250 46 250

480 3/3 48 250 48 250

500 3/3 50 250 50 250

520 3/3 52 250 52 250540 3/3 54 250 54 250560 3/3 56 250 56 250580 3/3 58 250 58 250600 4/4 60 250 60 250620 4/4 62 250 62 250

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Table 1. ALDOXORUBICIN-P3-STS-01RECONSTITUTION 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 InfusionVolume (mL)

640 4/4 64 250 64 250

660 4/4 66 250 66 250

680 4/4 68 250 68 250

700 4/4 70 250 70 250

720 4/4 72 250 72 250

740 4/4 74 250 74 250

760 4/4 76 250 76 250

780 4/4 78 250 78 250

800 5/5 80 250 80 250

820 5/5 82 250 82 250

840 5/5 84 250 84 250

860 5/5 86 250 86 250

880 5/5 88 250 88 250

900 5/5 90 250 90 250

920 5/5 92 250 92 250

940 5/5 94 250 94 250

960 5/5 96 250 96 250

980 5/5 98 250 98 250

1000 6/6 100 250 100 250

1020 6/6 102 250 102 250

1040 6/6 104 250 104 250