Study design

Timeline of phase 3 study. 14 day waiting period, Day 1 Triptodur 22.5 mg single IM injection, Day 169 week 24 Triptodur 22.5mg single IM injection. Day 337 week 48. [footnote a and b]

The efficacy and safety
of TRIPTODUR were
demonstrated in a multicenter
phase 3 study1,2

  • The study was an open-label, noncomparative, multicenter phase 3 trial on the efficacy and safety of triptorelin 22.5 mg 6-month formulation in patients with CPP. The study was conducted in 44 patients (n=39 girls; n=5 boys) with CPP aged 2 to 9 years who were naive to previous GnRH-agonist treatment.1,2
  • TRIPTODUR was initiated no more than 18 months after onset of the first signs of puberty.2
  • Eighteen medical centers in the United States, Chile, and Mexico participated in the study.2

Measurements Taken:
aMeasurement of serum LH, FSH, estradiol (girls), and testosterone (boys) levels collected at screening and at Months 1 (Day 29), 2 (Day 57), 3 (Day 85), 6 (Day 169), 9 (Day 253), and 12 (Day 337).1,2 LH and FSH were assessed both before and 30 minutes after stimulation with commercial leuprolide acetate 20 μg/kg subcutaneous injectable solution 1 mg/0.2 mL.1,2
bTransabdominal ultrasound was performed in girls; bone age was assessed by x-ray of the left hand and wrist. Collected during screening period, Month 6, and Month 12.2 Presence of unstable intracranial tumors at screening was excluded by MRI or CT scans of the brain, unless they had been performed within 3 months prior to treatment initiation.

Luteinizing hormone (LH) suppression to prepubertal levels1

Percentage of Patients Achieving Prepubertal LHa
(GnRH-Stimulated LH ≤5 IU/L)1,b

Month 1

Month 1 circular bar chart reaching 95% of the way around the circle. The center of the chart reads n/N=42/44

Month 6
(primary endpoint)

Month 6 circular bar chart reaching 93% of the way around the circle. The center of the chart reads n/N=41/44

Month 12

Month 12 circular bar chart reaching 98% of the way around the circle. The center of the chart reads n/N=43/44

93% of children
achieved LH
suppression with TRIPTODUR at
Month 6 (primary endpoint)1

TRIPTODUR demonstrated
LH suppression to prepubertal
levels as early as Month 11

98% of children
achieved LH suppression with TRIPTODUR at Month 121

Three patients presented with nonsuppressed LH levels at Month 6.2

  • Two of these nonresponders showed prepubertal levels at month 12, one of whom had a borderline LH value of 5.1 IU/L at month 6 but a suppressed testosterone level of 2 ng/dL. The other encountered a technical problem with the first injection, which is likely to have played a significant role regarding this treatment failure.
  • The third nonresponder was a 9-year-old overweight boy with a BMI of 23.1 kg/m2, who may have required a higher drug dose for adequate hormonal suppression, or may represent one of the rare children with CPP who do not achieve suppression with GnRH-agonists.

Note: 95% of children (n/N=42/44) achieved prepubertal LH levelsa at Months 2, 3, and 9.
aSerum LH ≤5 IU/L thirty minutes after GnRH-agonist stimulation.
bResults are from intent-to-treat (ITT) population.

Learn about dosing
and administration

Effective suppression of stimulated LH3

Line graph shows Mean LH, IU/L over time. Mean LH, IU/L drops sharply from above 25 to below 5 between day 14 and 29 and remains below 5 through day 337.

TRIPTODUR demonstrated
effective suppression of
stimulated LH throughout the study3

Mean LH remained
suppressed to prepubertal
levels (≤5 IU/L) at all time
points post-initiation of
TRIPTODUR3

Please go to section labeled "LH suppression to prepubertal levels" for more information about treatment nonresponders.

Effective suppression of sex steroids2

Line graph of LH and FSH, IU/L over time showing results of LH, FSH, Estradiol, 5 IU/L, and 20 ng/L. Date range from -14 to 337 days and line graph of LH and FSH, IU/L over time showing results of LH, FSH, Testosterone, 5 IU/L, and 30 ng/L. Date range from -14 to 337 days.

TRIPTODUR demonstrated
effective suppression
of sex steroids2

Suppression was achieved
from Week 4 through Week 482

Clinical signs of puberty

Infographic showing % of children achieving End Point footnote 1,2, a. 95% n/N=42/44 of children showed no increase in the BA/CA ratio at month 12 indicating a slowing of accelerated bone maturation [footnote b]. The Tanner stage was stable or reduced in 89% n/N=39/44 of patients between baseline and month 12 [footnote c]

TRIPTODUR arrested or reversed
progression of clinical signs of puberty1,2

77% of girls
(n/N=30/39) exhibited regression of uterine
length at Month 121

100% of boys
(n/N=5/5) showed absence of progression
of testicular volume at Month 121

aResults are from ITT population. bMonth 6 data: 64% (n/N=28/44). cMonth 6 data: 91% (n/N=40/44).
*Tanner stage refers to a scale used to measure the onset and progression of pubertal changes as determined by the physical development of secondary sex characteristics.4

Review safety
and tolerability
Learn about dosing
and administration

BA, bone age; BMI, body mass index; CA, chronological age; CPP, central precocious puberty; CT, computerized tomography; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; IM, intramuscular; ITT, intent-to-treat; LH, luteinizing hormone; MRI, magnetic resonance imaging.

IMPORTANT SAFETY INFORMATION FOR TRIPTODUR

INDICATION

TRIPTODUR is indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty (CPP).

IMPORTANT SAFETY INFORMATION

Contraindications

TRIPTODUR is contraindicated in:
  • Individuals with a known hypersensitivity to triptorelin or any other component of the product, or other GnRH agonists or GnRH.
  • Women who are or may become pregnant. Expected hormonal changes that occur with TRIPTODUR treatment increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be advised of the potential risk to the fetus.

Warnings and Precautions

Initial Rise of Gonadotropins and Sex Steroid Levels - During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug. Therefore, a transient increase in clinical signs and symptoms of puberty, including vaginal bleeding, may be observed during the first weeks of therapy or after subsequent doses.

Psychiatric Events - Psychiatric events have been reported in patients taking GnRH agonists. Postmarketing reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms during treatment with TRIPTODUR.

Convulsions - Postmarketing reports of convulsions have been observed in patients receiving GnRH agonists, including triptorelin. These included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above.

Pseudotumor Cerebri (idiopathic intracranial hypertension) - has been reported in pediatric patients receiving GnRH agonists, including triptorelin. Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.

Adverse Reactions

In clinical trials for TRIPTODUR, the most common adverse reactions (≥4.5%) are injection site reactions, menstrual (vaginal) bleeding, hot flush, headache, cough, and infections (bronchitis, gastroenteritis, influenza, nasopharyngitis, otitis externa, pharyngitis, sinusitis, and upper respiratory tract infection).

To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

The Important Safety Information does not include all the information needed to use TRIPTODUR safely and effectively. For additional safety information, please consult the full Prescribing Information for TRIPTODUR.

References

  1. 1. Triptodur [package insert]. Atlanta, GA: Arbor Pharmaceuticals, LLC. 2. Klein K, et al. Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. J Pediatr Endocrinol Metab. 2016;29(11):1241-1248. 3. Data on file. Arbor Pharmaceuticals, LLC. 4. Emmanuel M, Bokor BR. Tanner Stages. [Updated 2019 May 13]. StatPearls. (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470280/