Mechanism of Action

Triptorelin is a potent repressor of gonadotropin secretion when given continuously and in therapeutic doses. Following the first administration, there is a transient surge in circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and estradiol. After chronic and continuous administration, usually two to four weeks after initiation of therapy, a sustained decrease in LH and FSH secretion and marked reduction of testicular and ovarian steroidogenesis is observed. In men, a reduction of serum testosterone concentration to a level typically seen in surgically castrated men is obtained. Consequently, the result is that tissues and function that depend on these hormones for maintenance become quiescent. These effects are usually reversible after cessation of therapy.

Side Effects

Trelstar may cause the following side effects:

Fatigue

Nausea

Vomiting

Decreased blood cell counts

Hair loss

Mouth sores

Hot flushes

Loss of sexual drive

Breast tenderness

Nausea

Diarrhea

Dosing/Administration

Trelstar is supplied as a suspension to be administered as a single intramuscular injection in either buttock. Due to different release characteristics, the dosage strengths are not additive and must be selected based upon the desired dosing schedule. • 3.75 mg every four weeks. • 11.25 mg every 12 weeks. • 22.5 mg every 24 weeks.

Clinical Trial Results

TRELSTAR 3.75 mg 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 percent Caucasian, 39.3 percent Black, and 0.8 percent 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 nine 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 percent) patients and at day 57 in 97.7 percent of patients. Maintenance of castration levels of serum testosterone from day 57 through day 253 was found in 96.2 percent 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 twohours after repeat TRELSTAR 3.75 mg administration on days 85 and 169. One hundred twenty-four of the 126 evaluable patients (98.4 percent) 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 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 percent Caucasian, 38 percent Black, and 15 percent 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 three doses (maximum treatment period of 253 days) or TRELSTAR 3.75 mg (N = 172) every 28 days for a total of up to nine 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 percent of patients treated with TRELSTAR 11.25 mg. TRELSTAR 22.5 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 percent Caucasian, 23 percent Black, and 13 percent 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 two 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 percent (117 of 120) of patients treated with TRELSTAR 22.5 mg. Castration was maintained in 93.3percent of patients in the period from day 57 to day 337.