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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01223898

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: Tasigna	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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 Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nilotinib	Drug: Tasigna Other Names: AMN107

Arm

Intervention/Treatment

Experimental: Nilotinib

Drug: Tasigna

Other Names:

AMN107

Outcome Measures

Primary Outcome Measures

evaluate the effects of multiple doses of nilotinib on the pharmacokinetics and metabolism of midazolam in CML patients. [2 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Novartis Investigative Site	Frankfurt/M	Germany	60590
2	Novartis Investigative Site	Jena	Germany	07740
3	Novartis Investigative Site	Mannheim	Germany	68167
4	Novartis Investigative Site	Ulm	Germany	89081
5	Novartis Investigative Site	Glasgow	United Kingdom	G12 0YN