A 6-Month Trial of the Efficacy and Safety of Triptorelin Pamoate (11.25 mg) Every 3 Months in Children with Precocious Puberty: A Retrospective Comparison with Triptorelin Acetate

Abstract

Background/Aims: To evaluate the efficacy and safety of a triptorelin pamoate (11.25 mg) 3-month formulation in the management of central precocious puberty (CPP) (TP Study) and to retrospectively compare it with a triptorelin acetate (11.25 mg) 3-month formulation (TA Study). Methods: We conducted two phase III, multicentre, single-stage, non-comparative, open-label studies. In the TP Study, patients with CPP received an intramuscular injection of triptorelin pamoate 11.25 mg at baseline and 3 months after baseline. Hormonal changes as well as safety and efficacy endpoints were measured at baseline, 3 months, and 6 months. Results: The baseline characteristics of the 37 patients in the TP Study were similar to those of the TA Study population. A suppressed luteinising hormone (LH) response (LH peak ≤3 IU/l) to the gonadotrophin-releasing hormone test at 3 months (primary endpoint) occurred in 83.8 and 82.8% of the cases in the TP and the TA Study, respectively. At 6 months, a suppressed LH response occurred in 86.5 and 96.8% of the cases in the TP and the TA Study, respectively. Pubertal development was slowed in both studies. Adverse events were mild to moderate and resolved without sequelae in the TP Study. Conclusion: Triptorelin pamoate 11.25 mg administered at 3-month intervals is an effective and well-tolerated treatment in patients with CPP. The efficacy and safety profiles appear similar to those reported in the literature for triptorelin acetate 11.25 mg.

Meta-Analysis of Paediatric Patients with Central Precocious Puberty Treated with Intramuscular Triptorelin 11.25 mg 3-Month Prolonged-Release Formulation

“…Although no direct comparison between these 2 formulations was made in this study, both formulations appear efficacious for the treatment of CPP, which is in line with findings of the 1 previous study that compared triptorelin acetate with triptorelin pamoate [11]. …”

“…The proportion of children ( n = 101) with a suppressed response (GnRH-stimulated LH peak ≤3 IU/L) to the GnRH test at 12 months (no results for Bertelloni et al [8] or Zenaty et al [11]) was 89.1% (95% CI: 81.3–94.4, p < 0.0001, for a proportion >70%; Fig. 2b).…”

“…Triptorelin 11.25 mg 3-month formulation was well tolerated with most AEs being mild to moderate [4, 8, 10, 11]. The most frequent AEs were headache, rhinitis, and abdominal pain.…”

“…A comprehensive PubMed search was carried out, which identified 5 studies that were eligible for inclusion in a subsequent meta-analysis: 3 phase III Ipsen-sponsored studies and 2 independent publications [4, 8-11] (Table 1) by measuring the percentage of responder patients (GnRH-stimulated luteinising hormone [LH] peak <3 IU/L) 3 months after a single injection of triptorelin 11.25 mg. These studies were the only studies identified for the 3-month prolonged-release formulation of triptorelin on October 15, 2014, and all had similar objectives and efficacy endpoints.…”

“…Children recruited to the studies analysed in the meta-analysis met the following criteria: proven CPP defined as onset of sex characteristics development before the age of 8 years in girls and 9 years in boys based on the Tanner criteria consensus statement definition [1-3], with a pubertal response of LH to LH-releasing hormone in both sexes (stimulated LH >5 IU/L in Martinez-Aguayo et al [10] and Zenaty et al [11]; >6 IU/L in Bertelloni et al [8] or >7 IU/L in Carel et al [4] and Chiocca et al [9]), and a bone age >1 year ahead of the chronological age. As this was a retrospective study, no further ethical approval was sought beyond that obtained for all patients in the original studies.…”