Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adults with Congenital Adrenal Hyperplasia (CAH)
The safety of CRENESSITY in adults was assessed in Study 1, a randomized, double-blind, placebo-controlled study of 182 adults aged 18 to 58 years with classic CAH due to 21-hydroxylase deficiency. A total of 122 subjects received CRENESSITY 100 mg twice daily and 59 subjects received placebo twice daily for up to 24 weeks [see Clinical Studies (14.1)].
Adverse Reactions Leading to Discontinuation of Treatment
A total of 3% of CRENESSITY-treated subjects and no placebo-treated subjects discontinued treatment because of adverse reactions of restlessness, apathy, dyspepsia, nausea, and vomiting.
Commonly Observed Adverse Reactions
Adverse reactions that occurred in ≥4% of CRENESSITY-treated subjects and more frequently than in placebo-treated subjects are presented in Table 4.
Study 1 excluded subjects with active suicidal ideation with intent or plan within the six months prior to screening and those with a history of suicidal behavior within the past year, based on the Columbia-Suicide Severity Rating Scale (C-SSRS) administered at screening. The C-SSRS was administered to subjects at regular intervals during the study. Three of 122 (2.5%) CRENESSITY-treated subjects reported suicidal ideation without method, intent or plan on the C-SSRS during the 24-week double-blind treatment period compared to 1 of 59 (1.7%) placebo-treated subjects. One of the three subjects receiving CRENESSITY and the placebo-treated subject reported a lifetime history of suicidal ideation.
One CRENESSITY-treated subject without a history of suicidal ideation or behavior attempted suicide during the open-label period after 320 days of treatment.
Laboratory Findings
Neutrophil count less than 2 x 103 cells/mcL occurred in 14% (17 of 120) of CRENESSITY-treated subjects, compared to 5% (3 of 58) of subjects in the placebo group. Neutrophil count less than 1 x 103 cells/mcL occurred in 0.8% (1 of 120) of CRENESSITY-treated subjects, compared to 1.7% subjects (1 of 58) in the placebo group.
Pediatric Patients with Congenital Adrenal Hyperplasia
The safety of CRENESSITY in pediatric patients was evaluated in Study 2, a randomized, double-blind placebo-controlled study of 103 pediatric subjects aged 4 to 17 years with classic CAH due to 21-hydroxylase deficiency. Pediatric subjects were randomized to receive CRENESSITY twice daily (N=69) or placebo (N=34) for 28 weeks, using weight-based dosing (50 mg twice daily via oral solution for subjects 20 to <55 kg, or 100 mg twice daily via oral capsules for subjects ≥55 kg) [see Clinical Studies (14.2)].
Adverse Reactions Leading to Discontinuation of Treatment
A total of 3% of CRENESSITY-treated subjects and no placebo-treated subjects discontinued treatment because of adverse reactions of abdominal pain, myalgia, and dizziness.
Commonly Observed Adverse Reactions
Adverse reactions that occurred at an incidence of ≥4% in CRENESSITY-treated pediatric subjects (50 mg twice daily or 100 mg twice daily) and greater than placebo are presented in Table 5.
Table 5: Adverse Reactions (≥ 4%) in Pediatric Subjects with Congenital Adrenal Hyperplasia Treated with CRENESSITY and Occurring More Frequently Than in Placebo-Treated Subjects
1Abdominal pain includes: abdominal pain, abdominal pain upper and abdominal pain lower
Suicidal Ideation and Behavior
Study 2 excluded subjects with active suicidal ideation with intent or plan within six months prior to screening or those with a lifetime history of suicidal behavior based on the C-SSRS administered at screening. Four of 67 (6%) CRENESSITY-treated subjects and 0 of the 31 (0%) placebo-treated subjects reported suicidal ideation without method, intent or plan on the C-SSRS during the 28-week double-blind treatment period. Two of the four CRENESSITY-treated subjects reported a lifetime history of suicidal ideation. There were no completed suicides or suicide attempts.
Laboratory Findings
Neutrophil count less than 2 x 103 cells/mcL occurred in 37% (25 of 68) of CRENESSITY-treated subjects, compared to 16% (5 of 32) of subjects in the placebo group. Neutrophil count less than 1 x 103 cells/mcL occurred in 4% (3 of 68) of CRENESSITY-treated subjects, compared to no subjects (0 of 32) in the placebo group.