To Evaluate the Effects of Multiple Doses of Nilotinib on the Pharmacokinetics and Metabolism of Midazolam in CML Patients With Additional Extension Phase to Evaluate the Safety of Nilotinib

Study Overview
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Brief Summary
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This study will evaluate the effects of multiple doses of nilotinib on the pharmacokinetics and metabolism of midazolam (as a sensitive CYP3A probe) in CML patients. The following extension study does evaluate the safety of nilotinib.

Official Title
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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

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Drug: Tasigna


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a cytopathologically confirmed diagnosis of Ph+ CML or Philadelphia chromosome- negative (Ph-) CML patients in accelerated or chronic phase who are resistant and/or intolerant against at least one prior therapy with a BCR-ABL tyrosine kinase inhibitor Female or male ≥ 18 years of age Patients who are nilotinib naïve at study entry, e.g. did not receive any nilotinib treatment prior to study WHO Performance Status of ≤ 2 Exclusion Criteria: Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required). Impaired cardiac function History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis. Patients actively receiving therapy with the prohibited co-medications (CYP3A4 inhibitors or inducers, or CYP2C inducers) Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval Treatment with immunotherapy or chemotherapy within 3 days (6 weeks for nitrosurea or mitomycin-C) prior to Day 1 or who have not recovered from side effects of such therapy. Treatment with imatinib within 1 week prior to Day 1 or who have not recovered from side effects of such therapy. Patients who have hypersensitivity to midazolam or related compounds Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nilotinib<br> | Drug: Tasigna<br> <br> * Other names: AMN107;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate the effects of multiple doses of nilotinib on the pharmacokinetics and metabolism of midazolam in CML patients. |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate the safety and tolerability of multiple doses of nilotinib when midazolam is co-administered orally in CML patients. |  | 2 weeks | 
| Monitoring of safety of nilotinib during the extension study phase. |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CML,, nilotinib,, midazolam