This site is intended for
US Healthcare Professionals only.

Clinical Trials for Age 12 Years and Older

Safety and Efficacy Established in Two Phase 3 Studies in Patients Age 12 Years and Older1,2 

 

STUDY DESIGN

Trials 1 and 2 | Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Studies

Trials 1 and 2 were 24-week, Phase 3, randomized, double-blind, placebo-controlled studies of patients age 12 years and older with CF who were homozygous for the F508del-CFTR mutation, were clinically stable, and had a percent predicted FEV1 (ppFEV1) of 40-90 at screening. Patients received either ORKAMBI tablets (lumacaftor 400 mg/ivacaftor 250 mg q12h) or placebo with fat-containing food and continued to take their prescribed CF therapies. The primary endpoint in both trials was an absolute change in ppFEV1 from baseline at Week 24 assessed as the average of the treatment effects at Week 16 and at Week 24.1,2

 

Download the Short- and Long-term Clinical Data Brochure for ages 12 years and older.

 

SUMMARY OF RESULTS


ORKAMBI Improved and Sustained Lung Function and Other Key Clinical Outcomes1,2

  • In each trial, a hierarchical testing procedure was performed within each active treatment arm for primary and secondary endpoints vs placebo. For an endpoint to be significant, both it and all previous tests had to achieve P≤0.02502

    • Statistically significant endpoints are indicated by the shaded boxes in the table below
  • The safety of ORKAMBI was evaluated based on a pre-specified pooled analysis
  • A separate pooled analysis for efficacy was not pre-specified and did not correct for multiple comparisons.1,2 Secondary analyses of Trials 1 and 2 were conducted to evaluate efficacy

Please click below to download an overview of ORKAMBI clinical data

This includes Trials 1 and 2, as well as results from the long-term extension study and Rate of Change analyses.

THE OVERALL SAFETY PROFILE OF ORKAMBI IS BASED ON
POOLED DATA FROM TRIALS 1 AND 21


Discontinuation Due to Adverse Events1

ORKAMBI 5%; placebo 2% 

Serious Adverse Reactions1

  • Whether considered by investigators to be drug-related or not, serious adverse reactions that occurred more frequently in patients treated with ORKAMBI included the following (these occurred in ≤1% of patients):

    • Pneumonia
    • Hemoptysis
    • Increased blood creatine phosphokinase
    • Cough
    • Transaminase elevations
  • In Trials 1 and 2, the incidence of maximum transaminase (ALT or AST) levels >8, >5, and  >3 x ULN was similar between patients who received ORKAMBI vs placebo
  • 3 patients who received ORKAMBI had liver-related serious adverse reactions, including 2 reported as transaminase elevations and 1 as hepatic encephalopathy vs none in the placebo group

    • 1 of the 3 had elevated transaminases (>3 x ULN) associated with bilirubin elevation  (>2 x ULN). Following discontinuation or interruption of ORKAMBI, transaminases decreased to <3 x ULN
  • 1 of the 6 patients with pre-existing cirrhosis and/or portal hypertension who received ORKAMBI experienced worsening liver function with increased ALT, AST, bilirubin, and hepatic encephalopathy

    • The event occurred within 5 days of the start of dosing and resolved following discontinuation of ORKAMBI
  • In Trials 1 and 2, the incidence of respiratory symptom-related adverse reactions (eg, chest discomfort, dyspnea, and respiration abnormal) was more common in patients treated with ORKAMBI (22%) compared to patients who received placebo (14%)1

    • Respiration abnormal (chest tightness): ORKAMBI (9%) vs placebo (6%)
    • Dyspnea: ORKAMBI (13%) vs placebo (8%)
    • The incidence of these adverse reactions was more common in patients treated with ORKAMBI with lower pretreatment FEV1
  • Most respiratory symptom-related adverse events occurred within the first week of treatment and resolved within 2 weeks2
  • During a 24-week, open-label, Phase 3b clinical trial in 46 patients age 12 years and older (Trial 5) with advanced lung disease (ppFEV1 <40) [mean ppFEV1 29.1 at baseline (range: 18.3 to 42.0)], the incidence of respiratory symptom-related adverse reactions was 65%1

Menstrual Abnormalities1

  • In Trials 1 and 2, the incidence of combined menstrual abnormality adverse reactions (eg, amenorrhea, dysmenorrhea, menorrhagia, menstrual irregular) was more common in female patients treated with ORKAMBI (10%) compared to placebo (2%)
  • These events occurred more frequently in the subset of female patients treated with ORKAMBI who were using hormonal contraceptives (27%) compared to those not using hormonal contraceptives (3%)

Increased Blood Pressure1

  • In Trials 1 and 2, adverse reactions related to increases in blood pressure (eg, hypertension, blood pressure increased) were reported in 1.1% (4/369) of patients treated with ORKAMBI and in no patients who received placebo
  • The proportion of patients who experienced a systolic blood pressure value >140 mm Hg or a diastolic blood pressure >90 mm Hg on at least two occasions was 3.6% and 2.2%, respectively, in patients treated with ORKAMBI compared with 1.6% and 0.5% in patients who received placebo

   

TRIALS 1 AND 2 IN PATIENTS AGE 12 YEARS AND OLDER:
COMMON ADVERSE REACTIONS


Adverse Reactions in ≥5% of Patients Treated With ORKAMBI and at a Higher Rate Than Placebo1

Adverse Reactions
(Preferred Term)

ORKAMBI
n=369 (%)

Placebo
n=370 (%)

Dyspnea

48 (13)

29 (8)

Nasopharyngitis

48 (13)

40 (11)

Nausea

46 (13)

28 (8)

Diarrhea

45 (12)

31 (8)

Upper respiratory tract infection

37 (10)

20 (5)

Fatigue

34 (9)

29 (8)

Respiration abnormalc

32 (9)

22 (6)

Blood creatine
phosphokinase increased

27 (7)

20 (5)

Rash

25 (7)

7 (2)

Flatulence

24 (7)

11 (3)

Rhinorrhea

21 (6)

15 (4)

Influenza

19 (5)

8 (2)

cReported as chest tightness.2

Please click below to download an overview of ORKAMBI clinical data

This includes Trials 1 and 2, as well as results from the long-term extension study and Rate of Change analyses.

 

ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; BMI, body mass index; CFQ-R, cystic fibrosis questionnaire-revised; CI, confidence interval; IV, intravenous; LS, least squares; q12h, every 12 hours; ppFEV1, percent predicted forced expiratory volume in 1 second; ULN, upper limit of normal.