Lumacaftor

Pharmaceuticals -> Respiratory system -> Other respiratory system products

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals -> Listed in ZINC15

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

This chemical does not meet GHS hazard criteria for 50% (2 of 4) of reports.

Danger

H301 (25%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P260, P261, P264, P264+P265, P270, P271, P280, P301+P316, P301+P317, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 4 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Changes in sweat chloride in response to relevant doses of lumacaftor alone or in combination with ivacaftor were evaluated in a double-blind, placebo-controlled, Phase 2 clinical trial in patients with CF 18 years of age and older either homozygous or heterozygous for the F508del mutation. In that trial, 10 patients (homozygous for F508del) completed dosing with lumacaftor alone 400 mg q12h for 28 days followed by the addition of ivacaftor 250 mg q12h for an additional 28 days and 25 patients (homozygous or heterozygous for F508del) completed dosing with placebo. The treatment difference between lumacaftor 400 mg q12h alone and placebo evaluated as mean change in sweat chloride from baseline to Day 28 compared to placebo was -8.2 mmol/L (95% CI: -14, -2). The treatment difference between the combination of lumacaftor 400 mg/ivacaftor 250 mg q12h and placebo evaluated as mean change in sweat chloride from baseline to Day 56 compared to placebo was -11 mmol/L (95% CI: -18, -4). Changes in sweat chloride in response to lumacaftor/ivacaftor were also evaluated in a 24-week, open-label, clinical trial (Trial 3) in 58 patients with CF, aged 6 through 11 years (homozygous for F508del) who received lumacaftor 200 mg/ivacaftor 250 mg q12h for 24 weeks. Patients treated with lumacaftor/ivacaftor had a reduction in sweat chloride on Day 15 that was sustained through Week 24. The within-group LS mean absolute change from baseline in sweat chloride was -20.4 mmol/L on Day 15 and -24.8 mmol/L on Week 24. In addition, sweat chloride was also assessed after a 2-week washout period to evaluate the off-drug response. The within-group LS mean absolute change in sweat chloride from Week 24 to Week 26 following the 2-week washout period was 21.3 mmol/L. Changes in sweat chloride in response to lumacaftor/ivacaftor were also evaluated in a 24-week, open-label, clinical trial (Trial 6) in 60 patients with CF, aged 2 through 5 years (homozygous for F508del) who received either lumacaftor 100 mg/ivacaftor 125 mg every 12 hours or lumacaftor 150 mg/ivacaftor 188 mg every 12 hours for 24 weeks. Treatment with lumacaftor/ivacaftor demonstrated a reduction in sweat chloride at Week 4 that was sustained through Week 24. The mean absolute change from baseline in sweat chloride was –31.7 mmol/L (95% CI: -35.7, -27.6) at Week 24. In addition, sweat chloride was also assessed after a 2-week washout period to evaluate the off-drug response. The mean absolute change in sweat chloride from Week 24 to Week 26 following the 2-week washout period was an increase of 33.0 mmol/L (95% CI: 28.9, 37.1; P<0.0001). Changes in sweat chloride in response to lumacaftor/ivacaftor were evaluated in a 24-week, open-label, clinical trial (Trial 7) in 46 patients with CF, aged 1 through 2 years (homozygous for F508del) who received lumacaftor 75 mg/ivacaftor 94 mg (patient weighing 7 kg to <9 kg at screening), lumacaftor 100 mg/ivacaftor 125 mg (patient weighing 9 kg to <14 kg at screening), lumacaftor 150 mg/ivacaftor 188 mg (patient weighing ≥14 kg at screening), every 12 hours for 24 weeks. Treatment with lumacaftor/ivacaftor demonstrated a reduction in sweat chloride at Week 4 which was sustained through Week 24. The mean absolute change from baseline in sweat chloride at Week 24 was -29.1 mmol/L (95% CI: -34.8, -23.4). In addition, sweat chloride was also assessed after a 2-week washout period to evaluate the off-drug response. The mean absolute change in sweat chloride from Week 24 at Week 26 following the 2-week washout period was 27.3 mmol/L (95% CI: 22.3, 32.3). There was no direct correlation between the decrease in sweat chloride levels and an improvement in lung function (ppFEV1). The effect of multiple doses of lumacaftor 600 mg once daily/ivacaftor 250 mg q12h and lumacaftor 1000 mg once daily/ivacaftor 450 mg q12h on QTc interval was evaluated in a randomized, placebo- and active-controlled (400 mg moxifloxacin), parallel, thorough QT study in 168 healthy subjects. No meaningful changes in QTc interval were observed with either lumacaftor 600 mg once daily/ivacaftor 250 mg q12h and lumacaftor 1000 mg once daily/ivacaftor 450 mg q12h dose groups. A maximum decrease in mean heart rate of up to 8 beats per minute (bpm) from baseline was observed with lumacaftor/ivacaftor treatment. In Trials 1 and 2, a similar decrease in heart rate was observed in patients during the initiation of ORKAMBI (lumacaftor 400 mg/ivacaftor 250 mg q12h). Results from two randomized, double-blind, placebo-controlled, 24-week clinical trials of Orkambi (lumacaftor/ [DB08820]) indicates that a lung function improvement, as demonstrated by a mean absolute change in ppFEV1 from baseline at Week 24 of 2.6 percentage points [95% CI (1.2, 4.0)] in Trial 1 (P=0.0003) and 3.0 percentage points [95% CI (1.6, 4.4)] in Trial 2.