Study design
This multicenter, open-label, single-sequence study (NCT02626234) consisted of a molecular pre-screening period, a screening/baseline period, a DDI phase and post-DDI phase or treatment phase (Fig. 1 ).
Baseline evaluations were performed within 28 days prior to the first dose of the probe drugs (digoxin and rosuvastatin). In the DDI phase (Day 1 to Day 32), a single oral dose of two probe drugs was administered as a two-drug cocktail on Day 1. No treatment was administered from Day 2 to Day 10 (washout phase). From Day 11 to Day 21, capmatinib tablets (400 mg twice daily, given 12 hours apart) were administered on a continuous dosing schedule. On Day 22, the two probe drugs and capmatinib were administered together. Administration of capmatinib 400 mg twice daily was continued until the end of the DDI phase (from Day 23 to Day 32). From Day 22 onwards, pharmacokinetic samples were collected relative to the end of the probe drugs ingestion for measurement of digoxin, rosuvastatin and capmatinib plasma concentrations at various time points during the DDI phase. All patients who entered the DDI phase were required to have an end of phase visit after the DDI phase. After completion of the DDI phase, patients were allowed to continue treatment with capmatinib 400 mg twice daily, administered orally on continuous 21-day cycles. All patients who entered the post-DDI phase were required to have an end of treatment visit. When the patient discontinued from the post-DDI phase, the end of treatment visit was performed as soon as possible and within 7 days of the last dose.
Patients were contacted for a safety follow-up 30 days after the last dose of study treatment, regardless of the reason for discontinuation from study treatment. Any adverse events (AEs) or serious adverse events (SAEs) occurred after discontinuation of study treatment and follow-up on resolution of ongoing AEs were recorded. If the study drug was discontinued for reasons other than documented disease progression or withdrawal of consent, patients were followed-up with tumor assessments until progression determined by investigator’s assessments, start of new anticancer therapy or death.