Interaction between nilotinib and midazolam in CML patients

• Research type

  Research Study

• Full title

  An open-label, two-period, fixed-sequence study to evaluate the effects of multiple doses of nilotinib on the pharmacokinetics of midazolam in CML patients who are resistant and/or intolerant against at least one prior therapy with a BCR-ABL tyrosine kinase inhibitor

• IRAS ID

  44541

• Contact name

  Tessa Holyoake

• Sponsor organisation

  Novartis Pharma Services AG

• Eudract number

  2009-009425-28

• Clinicaltrials.gov Identifier

  01223898

• Research summary

  Leukaemia is a cancer of the white blood cells. Normally, white blood cells grow and divide in an orderly and controlled way, but in leukaemia the process gets out of control and the cells divide too quickly, and do not mature properly. Chronic Myeloid Leukaemia (CML) is a rare type of cancer affecting the myeloid cells (one of the main types of white blood cells); approximately 750 new cases are diagnosed in the UK each year, these being mostly adults aged 40-60 years. CML usually develops very slowly displaying few noticeable symptoms. However, if left untreated CML can progress causing large numbers of cancer cells to build up in the bone marrow leading to serious health implications. Nilotinib is an approved treatment for CML in patients who have previously been treated with imatinib and become either resistant or intolerant to the treatment. Nilotinib is degraded in the body by specific enzymes in a process called metabolism. Metabolism is an important chemical mechanism to inactivate and eliminate drugs from the human body. Midazolam is a drug that is metabolised by one of these enzymes (CYP3A). Novartis Pharmaceuticals is sponsoring a study to evaluate the effect of multiple doses of nilotinib on the metabolism of midazolam. Approximately 22 participants from study centres in the UK and Germany will receive: ?½ DAY 1: Midazolam (1 x 2 mg dose)?½ DAY 2-12: Nilotinib: (2x 400 mg dose per day)?½ DAY13: Midazolam (1 x 2 mg dose) Nilotinib: (2x 400 mg dose)Participants will remain in hospital overnight on two occasions for safety monitoring (DAY -1 to 2 and DAY 12 to 14). There is an optional extension phase for participants who continue on Nilotinib, this will involve 2 visits (6 and 12 months).

• REC name

  West of Scotland REC 1

• REC reference

  10/S0703/36

• Date of REC Opinion

  6 Jul 2010

• REC opinion

  Further Information Favourable Opinion