Clinical trial NCT01223898: 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
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Myeloid Leukemia
Keywords: CML,
nilotinib,
midazolam
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-10-19
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Female or male ≥ 18 years of age
3. Patients who are nilotinib naïve at study entry, e.g. did not receive any nilotinib treatment prior to study
4. WHO Performance Status of ≤ 2

Exclusion Criteria:

1. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
2. Impaired cardiac function
3. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
4. Patients actively receiving therapy with the prohibited co-medications (CYP3A4 inhibitors or inducers, or CYP2C inducers)
5. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval
6. 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.
7. Treatment with imatinib within 1 week prior to Day 1 or who have not recovered from side effects of such therapy.
8. Patients who have hypersensitivity to midazolam or related compounds

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: evaluate the effects of multiple doses of nilotinib on the pharmacokinetics and metabolism of midazolam in CML patients.
timeFrame: 2 weeks
Secondary outcomes:
measure: evaluate the safety and tolerability of multiple doses of nilotinib when midazolam is co-administered orally in CML patients.
timeFrame: 2 weeks
measure: Monitoring of safety of nilotinib during the extension study phase.
timeFrame: 12 months
Other outcomes:
Locations:
city: Frankfurt/M
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: