Trelstar

TRELSTAR 3.75 mg was studied in a randomized, active control trial of 277 men with advanced prostate cancer.  The clinical trial population consisted of 59.9% Caucasian, 39.3% Black, and 0.8% Other.  There was no difference observed with triptorelin response between racial groups.  Men were between 47 and 89 years of age (mean = 71 years).  Patients received either TRELSTAR 3.75 mg (N = 140) or an approved GnRH agonist monthly for 9 months.  The primary efficacy endpoints were both achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 253.

Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) in patients treated with TRELSTAR 3.75 mg were achieved at Day 29 in 125 of 137 (91.2%) patients and at Day 57 in 97.7% of patients. Maintenance of castration levels of serum testosterone from Day 57 through Day 253 was found in 96.2% of patients treated with TRELSTAR 3.75 mg.

The presence of an acute-on-chronic flare phenomenon was also studied as a secondary efficacy endpoint.  Serum LH levels were measured at 2 hours after repeat TRELSTAR 3.75 mg administration on Days 85 and 169.  One hundred twenty-four of the 126 evaluable patients (98.4%) on Day 85 had a serum LH level of ≤ 1.0 IU/L at 2 hours after dosing, indicating desensitization of the pituitary gonadotroph receptors.

TRELSTAR 11.25 mg was studied in a randomized, active control trial of 346 men with advanced prostate cancer.  The clinical trial population consisted of 48% Caucasian, 38% Black, and 15% Other.  There was no difference observed with triptorelin response between racial groups.  Men were between 45 and 96 years of age (mean = 71 years).  Patients received either TRELSTAR 11.25 mg (N = 174) every 12 weeks for a total of up to 3 doses (maximum treatment period of 253 days) or TRELSTAR 3.75 mg (N = 172) every 28 days for a total of up to 9 doses.  The primary efficacy endpoints were both achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 253.

Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) were achieved at Day 29 in 167 of 171 (97.7%) patients treated with TRELSTAR 11.25 mg, and maintenance of castration levels of serum testosterone from Day 57 through Day 253 was found in 94.4% of patients treated with TRELSTAR 11.25 mg.

TRELSTAR 22.5 mg was studied in a non-comparative trial of 120 men with advanced prostate cancer.  The clinical trial population consisted of 64% Caucasian, 23% Black, and 13% Other, with a mean age of 71.1 years (range 51-93).   Patients received TRELSTAR 22.5 mg (N = 120) every 24 weeks for a total of 2 doses (maximum treatment period of 337 days).  The primary efficacy endpoints included achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 337.

Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) were achieved at Day 29 in 97.5% (117 of 120) of patients treated with TRELSTAR 22.5 mg. Castration was maintained in 93.3% of patients in the period from Day 57 to Day 337.

A summary of the clinical studies for TRELSTAR is provided in Table 7.

^*Maintenance of castration was calculated using a frequency distribution.

^†Cumulative maintenance of castration was calculated using a survival analysis (Kaplan-Meier) technique.

^‡Calculation includes 5 patients who discontinued the study but who had castrate levels of testosterone prior to discontinuation.

TRELSTAR must be administered under the supervision of a physician.

TRELSTAR is administered by a single intramuscular injection in either buttock.  Dosing schedule depends on the product strength selected (Table 1).  The lyophilized microgranules are to be reconstituted in

Due to different release characteristics, the dosage strengths are not additive and must be selected based upon the desired dosing schedule.

The suspension should be administered within 2 minutes after reconstitution.

As with other drugs administered by intramuscular injection, the injection site should be alternated periodically.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

*The strength indicated on the vial in the figure above is for representative purposes only. All three strengths of the Trelstar vial have their individual strengths indicated on the label. Users will see either 3.75 mg, 11.25 mg or 22.5 mg, with the corresponding duration of treatment (4, 12 or 24 weeks respectively).

Check that you are using the prescribed strength/dose (3.75 mg, 11.25 mg, or 22.5 mg) and that the expiry date has not passed, before preparation and activation.

Wash your hands with soap and hot water and put on gloves immediately prior to preparing the injection.  Place the sealed tray on a clean, flat surface that is covered with a sterile pad or cloth.  Peel the cover away from the tray and remove the injection kit components and TRELSTAR vial.

• The product is a suspension of microgranules that can settle in the diluent. The final product to be administered is a suspension of microgranules with a milky, homogeneous appearance. If the product settles in the vial, shake it again to resuspend the microgranules.

• If the microgranules settle in the syringe, this will block the needle during administration. It is very important to inject the product within 2 minutes following reconstitution in the vial. If the product settles in the syringe, draw some air back into the syringe, shake it again, and expel the air (without priming the needle) before administering it.

	STEP 1 – PREPARE VIAL Remove the flip-off button cap from the vial, revealing the rubber stopper. Place the vial in a standing upright position on the prepared surface. Disinfect the rubber stopper with the alcohol wipe. Discard the alcohol wipe and allow the stopper to dry.
	STEP 2 – APPLY VIAL ADAPTER Peel the cover away from the blister pack containing the vial adapter. Do not remove the vial adapter from the blister pack . On a level surface, place the blister pack containing the vial adapter firmly on the vial top. Ensure the spike is centered and vertical when piercing the vial . Push down gently until you feel it snap into place. Remove the blister pack from the vial adapter.
	STEP 3 – PREPARE SYRINGE AND CONNECT TO VIAL ADAPTER (a) Grasp the plastic ‘spin lock’ collar on the syringe barrel with index finger and thumb. Unscrew and discard the gray rubber cap from the syringe barrel. (b) Maintaining your grip on the spin lock, attach the syringe to the vial adapter by screwing the spin lock clockwise onto the vial adapter luer lock. Gently twist the spin lock until it stops turning to ensure a tight connection. Note: Overtightening can result in a poor connection and leakage.
	STEP 4 – TRANSFER DILUENT TO VIAL Holding the vial and adapter with one hand, slowly push the plunger rod with the other hand and transfer all of the diluent into the vial.
	STEP 5 – MIX TRELSTAR SUSPENSION Gripping the vial and vial adapter firmly, shake vigorously for 30 seconds to mix the contents thoroughly . This will ensure complete mixing of TRELSTAR and the sterile water diluent. Check the appearance of the suspension through the bottom of the vial. The suspension should appear homogeneous and milky. In order to avoid separation of the suspension, proceed to the next steps without delay. The product must be injected within less than 2 minutes from reconstitution. Note: If there is sedimentation in the vial, shake again.
	STEP 6 – LOAD THE SYRINGE WITH TRELSTAR (a) Immediately invert the system so that the vial is at the top and the syringe is at the bottom. Pull back the plunger rod slowly to draw the reconstituted TRELSTAR into the syringe while maintaining pressure on the plunger rod to ensure it does not pull back too far. (b) Remove air bubbles by expelling air into the vial but do not propel the suspension beyond the luer lock. Note : If the product settles in the syringe, draw some air back into the syringe, shake it again, and expel the air (without priming the needle) before administering it.
	STEP 7 – DISCONNECT VIAL ADAPTER AND CONNECT NEEDLE (a) Hold the barrel and spin lock firmly. Hold the syringe barrel and spin lock with one hand and with the other hand turn the adapter counter-clockwise to disconnect the vial adapter and vial from the syringe. (b) Holding the syringe by the spin lock, attach the injection needle
	STEP 8 – PREPARE FOR INJECTION Make sure that the patient is ready for the administration. Lift up the safety cover and remove the clear plastic needle shield by pulling it from the assembly. The safety cover should be perpendicular to the needle, with the needle facing away from you. Do not prime the needle. The syringe containing the TRELSTAR suspension is now ready for administration. The suspension should be administered immediately (less than 2 minutes) after reconstitution to avoid excessive thickening of the suspension.
	STEP 9 – ADMINISTRATION Administer the injection by inserting the needle at a 90-degree angle into the large gluteal muscle. Ensure that the full amount of the product is injected within 10 seconds without interruption. Injection sites should be alternated.
	STEP 10 – SAFETY LOCK AFTER INJECTION After administering the injection, immediately activate the safety mechanism by centering your thumb or forefinger on the textured finger pad area of the safety cover and pushing it forward over the needle until you hear or feel it lock in place. Use the one-handed technique and activate the mechanism away from yourself and others. Immediately discard the syringe into a sharps container after a single use.