Roniciclib (BAY 1000394) Drug-Drug Interaction (DDI) Study

Phase 1

Completed

• Conditions: Medical Oncology
• Interventions: Drug: Roniciclib (BAY 1000394); Drug: Itraconazole (Sporanox)

• Registration Number: NCT02457351
• Lead Sponsor: Bayer

Brief Summary

To evaluate the effect of itraconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics of roniciclib in cancer patients.

To assess safety and tolerability of roniciclib dosing when administered with and without itraconazole in cancer patients

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-05-28
• Study First Submitted QC: 2015-05-28
• Study First Posted: 2015-05-29
• Study Start: 2015-07
• Primary Completion: 2016-02
• Study Completion: 2016-04
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-20
• Last Update Posted: 2016-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

• Male or female patients ≥ 18 years of age with histological or cytological confirmed advanced solid tumors refractory to, or not able to tolerate to any standard therapy, have no standard therapy available, or subjects must have actively refused any treatment which would be regarded standard, and / or if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable.
• Adequate liver, renal and bone-marrow functions as assessed by laboratory values.
• ECOG Performance Status of 0 - 2 and life expectancy of at least 12 weeks.
• Subject with a history of hypertension should be on a stable anti-hypertensive treatment for more than 7 days prior to the first dose of study drug.

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Exclusion Criteria

Medical and surgical history:

• Previous deep vein thrombosis (within the last 6 months), arterial thrombotic events (including strokes), or pulmonary embolism.
• History of cardiac disease: congestive heart failure, angina (within past 6 months prior to study entry), myocardial infarction, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
• Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg despite optimal medical management)
• Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C. History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• Active clinically serious infections of Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03) > Grade 2.
• Symptomatic metastatic brain or meningeal tumors unless the subject is >3 months from definitive therapy, has no evidence of tumor growth on an imaging study within 4 weeks prior to study entry, and is clinically stable with respect to the tumor at the time of study entry.
• Seizure disorder requiring therapy (such as steroids or anti-epileptics).
• History of organ allograft.
• Use of strong inhibitors and/or inducers of CYP3A4 in the 14 days before study treatment

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Roniciclib + Itraconazole	Roniciclib (BAY 1000394)	Pharmacokinetics and safety in patients with advanced solid tumor
Roniciclib + Itraconazole	Itraconazole (Sporanox)	Pharmacokinetics and safety in patients with advanced solid tumor

Primary Outcome Measures

Name	Time	Method
Area under the concentration vs. time curve from zero to infinity (AUC) of roniciclib on Cycle 1 Day 1 (without itraconazole)	Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 24, 48 and 72 hours after dosing
Maximum observed drug concentration (Cmax) of roniciclib on Cycle 1 Day 6 (with itraconazole)	Cycle 1 Day 6: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96 and 120 hours after dosing
Maximum observed drug concentration (Cmax) of roniciclib on Cycle 1 Day 1 (without itraconazole)	Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 24, 48 and 72 hours after dosing
Area under the concentration vs. time curve from zero to infinity (AUC) of roniciclib on Cycle 1 Day 6 (with itraconazole)	Cycle 1 Day 6: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96 and 120 hours after dosing

Secondary Outcome Measures

Name	Time	Method
Physical examination to assess safety and tolerability of roniciclib dosing when administered with and without itraconazole	up to 15 months
Maximum observed drug concentration (Cmax) of roniciclib after a light meal on Cycle 1 Day -2 (without itraconazole)	Cycle 1 Day -2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after dosing
Area under the concentration vs. time curve from zero to 24 hr (AUC) of roniciclib after a light meal on Cycle 1 Day -2 (without itraconazole)	Cycle 1 Day -2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after dosing
Monitoring of vital signs to assess safety and tolerability of roniciclib dosing when administered with and without itraconazole	up to 15 months
East Coast Oncology Group (ECOG) performance status to assess safety and tolerability of roniciclib dosing when administered with and without itraconazole	up to 15 months
Electrocardiogram (12 lead ECG) readings to assess safety and tolerability of roniciclib dosing when administered with and without itraconazole	up to 15 months
Collection of Adverse events as a measure of safety and tolerability of roniciclib dosing when administered with and without itraconazole	up to 15 months
Laboratory analyses to assess safety and tolerability of roniciclib dosing when administered with and without itraconazole	up to 15 months	Complete blood count, Complete chemistry panel, Coagulation panel, Virology, Urinalysis, Pregnancy test