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

Chronic Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01223898
• Other study ID #: CAMN107A2128
• Secondary ID: 2009-009425-28
• Status: Completed
• Phase: Phase 1
• Start date: June 2010
• Est. completion date: December 2013

Study information

• Verified date: April 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention

Drug:
• Tasigna

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Frankfurt/M
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Ulm
United Kingdom	Novartis Investigative Site	Glasgow

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	evaluate the effects of multiple doses of nilotinib on the pharmacokinetics and metabolism of midazolam in CML patients.		2 weeks
Secondary	evaluate the safety and tolerability of multiple doses of nilotinib when midazolam is co-administered orally in CML patients.		2 weeks
Secondary	Monitoring of safety of nilotinib during the extension study phase.		12 months

External Links

•   Results for CAMN107A2128 can be found on the Novartis Clinical Trial Results Website