SAFETY PROFILE

Safety data from 510 patients with CF in 2 double‑blind, controlled, Phase 3 trials of 24 weeks (Trial 1) and 4 weeks (Trial 2) treatment duration1 

  • A total of 257 patients with CF aged 12 years and older received at least one dose of TRIKAFTA
  • Except where otherwise noted, the safety data provided below are from Trial 1, the placebo-controlled 24-week trial with patients heterozygous for F508del and another specific mutation. The safety profile in patients with CF enrolled in Trial 2 was similar to that observed in Trial 1 
  • With the exception of sex differences in rash, the safety profile of TRIKAFTA was generally similar across all subgroups of patients regardless of age, sex, baseline ppFEV₁, and geographic region 

Adverse event-related discontinuations1,2 

1% OF PATIENTS
TREATED WITH TRIKAFTA (n=2)

0% OF PATIENTS
TREATED WITH PLACEBO (n=0)

Serious adverse reactions1,3 

  • In Trials 1 and 2, serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0). There were no deaths in Trials 1 and 2

Most common adverse reactions in Trial 11 
 

Incidence of adverse drug reactions in5% of patients treated with TRIKAFTA™ (elexacaftor/tezacaftor/ivacaftor and ivacaftor) and higher than placebo by 1%
TRIKAFTA n (%) (N=202)
Placebo n (%) (N=201)
Headache
35 (17)
30 (15)
Upper respiratory tract infectiona
32 (16)
25 (12)
Abdominal painb
29 (14)
18 (9)
Diarrhea
26 (13)
14 (7)
Rashc
21 (10)
10 (5)
ALT increased
20 (10)
7 (3)
Nasal congestion
19 (9)
15 (7)
Blood CPK increased
19 (9)
9 (4)
AST increased
19 (9)
4 (2)
Rhinorrhea
17 (8)
6 (3)
Rhinities
15 (7)
11 (5)
Influenza
14 (7)
3 (1)
Sinusitis
11 (5)
8 (4)
Blood bilirubin increased
10 (5)
2 (1)

aIncludes upper respiratory tract infection and viral upper respiratory tract infection.
bIncludes abdominal pain, abdominal pain upper, and abdominal pain lower.
cIncludes rash, rash generalized, rash erythematous, rash macular, and rash pruritic.

  • Additional adverse reactions that occurred in TRIKAFTA-treated patients at a frequency of 2 to <5% and higher than placebo ≥1% include the following: Flatulence, abdominal distension, conjunctivitis, pharyngitis, respiratory tract infection, c-reactive protein increased, hypoglycemia, dizziness, dysmenorrhea, acne, eczema, and pruritus

Rash events1

  • The overall incidence of rash events was 10% in patients treated with TRIKAFTA and 5% in placebo-treated patients
  • The incidence of rash events was higher in female patients treated with TRIKAFTA (16%) than in male patients treated with TRIKAFTA (5%)
  • Hormonal contraceptives may play a role in the occurrence of rash. For patients taking hormonal contraceptives who develop rash, consider interrupting TRIKAFTA and hormonal contraceptives. Following the resolution of rash, consider resuming TRIKAFTA without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered

Additional information on rash4

  • The median time to onset of first rash event was 12 days (range 5-157 days) in patients treated with TRIKAFTA and 23 days (range 1-157 days) in placebo-treated patients. The median duration of rash events was 8 days (range 1-92 days) in patients treated with TRIKAFTA and 9 days (range 3-61 days) in placebo-treated patients
  • The rash events were exanthematous—consistent with a typical drug eruption

Laboratory and vital sign abnormalities

Liver function test elevations1,5

Incidence of maximum transaminases and maximum total bilirubin elevations in Trials 1
TRIKAFTA (N=202)
Elevated ALT or AST, n (%) >3x ULN 16 (8)
>5x ULN 5 (2)
>8x ULN 3 (1)
Total bilirubin elevation >2x ULN, % 4
Placebo (N=201)
Elevated ALT or AST, n (%) >3x ULN 11 (5)
>5x ULN 3 (1)
>8x ULN 2 (1)
Total bilirubin elevation >2x ULN, % <1

 

  • The incidence of adverse reactions of transaminase elevations (AST and/or ALT) was 11% in patients treated with TRIKAFTA and 4% in placebo-treated patients1
  • No patients treated with TRIKAFTA discontinued due to transaminase elevations2
  • Maximum indirect bilirubin elevations >1.5x ULN occurred in 11% of patients treated with TRIKAFTA. Maximum direct bilirubin elevations >1.5x ULN occurred in 3% of patients treated with TRIKAFTA1
  • No patients treated with TRIKAFTA developed maximum direct bilirubin elevation >2x ULN1

Increased CPK1

  • The incidence of maximum CPK >5x ULN was 10% in patients treated with TRIKAFTA and 5% in placebo-treated patients
  • Among the patients treated with TRIKAFTA with CPK elevation >5x ULN, 14% (3/21) required treatment interruption and none discontinued treatment

Increased blood pressure1

Maximum increase from baseline in mean blood pressure
Mean systolic blood pressure (mmHg)

TRIKAFTA
(N=202)

Baseline

113

Maximum increase from baseline

3.5

Placebo
(N=201)

Baseline

114

Maximum increase from baseline

0.9

Mean diastolic blood pressure (mmHg)

TRIKAFTA
(N=202)

Baseline

69

Maximum increase from baseline

1.9

Placebo
(N=201)

Baseline

70

Maximum increase from baseline

0.5

  • The proportion of patients who had an increase in systolic blood pressure of >140 mmHg and 10 mmHg increase from baseline on at least two occasions:
    • 4% of patients treated with TRIKAFTA and 1% of placebo-treated patients
  • The proportion of patients who had an increase in diastolic blood pressure of >90 mmHg and 5 mmHg increase from baseline on at least two occasions:
    • 1% of patients treated with TRIKAFTA and 2% of placebo-treated patients
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ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase; ULN, upper limit of normal.