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

An Open-label, Non-randomized, Phase I Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of a Single Oral Dose of Roniciclib in Patients With Advanced Solid Tumors

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

Study Overview

• Status: Completed
• Conditions: Medical Oncology
• Intervention / Treatment: Drug: Roniciclib (BAY 1000394); Drug: Itraconazole (Sporanox)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
    • London, Ontario, Canada, N6A 4L6
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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

Study Plan

How is the study designed?

Design Details

• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Roniciclib + Itraconazole; Pharmacokinetics and safety in patients with advanced solid tumor

Drug: Roniciclib (BAY 1000394); Part 1 of Cycle 1 Cycle 1 Day 1: Single dose 2.5 mg Cycle 1 Day 6: Single dose 2.5 mg Part 2 of Cycle 1 Cycle 1 Day 1: Single dose 2.5 or 5 mg (based on Part 1 data) Cycle 1 Day 6: Single dose 2.5 or 5 mg (based on part 1 data) Part 1 & Part 2 Cycle 2 and subsequent 21-day cycles: Day 1-3 of each cycle: 5 mg bid Day 4-7 of each cycle: no dose; Drug: Itraconazole (Sporanox); Part 1 & Part 2 of Cycle 1 Cycle 1 Day 4: 200 mg bid Cycle 1 Day 5-11: 200 mg qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 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
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

Outcome Measure	Measure Description	Time Frame
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	Complete blood count, Complete chemistry panel, Coagulation panel, Virology, Urinalysis, Pregnancy test	up to 15 months
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
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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: May 28, 2015
• First Posted (Estimate): May 29, 2015

Study Record Updates

• Last Update Posted (Estimate): May 23, 2016
• Last Update Submitted That Met QC Criteria: May 20, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Phase 1; Advanced solid tumor; Drug-drug Interaction; pan-CDK inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 17616 (Other Identifier: Abramson Cancer Center)