Drug Interaction Study of SAR302503 in Patients With Solid Tumor

An Open-label, Two-treatment Crossover Pharmacokinetic Interaction Study of Repeated Doses of SAR302503 on Pharmacokinetics of a Single Dose Cocktail of Omeprazole, Metoprolol, and Midazolam Used as Probe Substrates for CYP2C19, CYP2D6 and CYP3A4 Activities, Respectively in Adult Patients With Refractory Solid Tumors

Primary Objective:

• To assess the effect of 15-day repeated oral doses of 500 mg SAR302503 on the cytochrome P450 activity using a CYP probe cocktail (2C19, 2D6 and 3A4).
• To document pharmacokinetics of SAR302503 after repeated 500 mg oral daily doses.

Secondary Objectives:

• To assess the safety profile of 15-day repeated oral doses of 500 mg SAR302503 in Segment 1
• To characterize the safety and tolerability of 28-day consecutive doses of 500 mg SAR302503 in Segment 2
• To determine antitumor activity in Segment 2

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: SAR302503; Drug: omeprazol; Drug: metoprolol; Drug: midazolam

Detailed Description

The duration of the study for an individual patient will include a period to assess eligibility (screening period 21 days), followed by a treatment period of at least 15 days of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue if patients are receiving benefit and do not have unacceptable toxicity or meet study withdrawal criteria.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Investigational Site Number 840004
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Investigational Site Number 840001
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Investigational Site Number 840002

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 :

• Histologically or cytologically confirmed advanced solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist
• Signed informed consent

Exclusion criteria:

• Less than 18 years of age.
• Limited physical functioning (as evaluated by the Eastern Cooperative Oncology Group (ECOG) scale)
• Inability to follow study requirements and schedule
• Treatment of cancer within 3 weeks of study, concurrent treatment in another clinical trial or with any other anti-cancer therapy
• Serious medical illness at same time of study and/or significantly abnormal lab reports
• Lack of pregnancy contraception (women of childbearing potential), pregnancy, or breast feeding.
• Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on study drug
• Continued toxic effects of prior chemotherapy
• Evidence of other concurrent active malignancy
• Other concurrent serious illness or medical condition
• Cardiac abnormalities include bradycardia, AV block or other conduction defect on ECG, and patients taking a beta blocker.
• Patients with Insulin-Dependent Diabetes Mellitus.
• Patients with known active (acute or chronic) hepatitis A, B, C, and hepatitis B and C carries. Prior history of chronic liver disease (e.g., chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH]).
• Inadequate organ function
• History of partial or total gastrectomy, or, if in the opinion of the investigator, have any other disorder that would inhibit absorption of oral medications.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Segment 1; two single doses of omeprazol/metoprolol/midazolam on day-1 and day 15 without food, SAR302503 500 mg once daily without food for 15 days	Drug: SAR302503; Pharmaceutical form:capsule Route of administration: oral; Drug: omeprazol; Pharmaceutical form:capsule Route of administration: oral; Drug: metoprolol; Pharmaceutical form:tablet Route of administration: oral; Drug: midazolam; Pharmaceutical form:solution Route of administration: oral
EXPERIMENTAL: Segment 2; SAR302503 500 mg once daily without food in 28-day per cycle	Drug: SAR302503; Pharmaceutical form:capsule Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Omerprazole/metoprolol/midazolam - Pharmacokinetic parameter: AUC, AUClast	predose and up to 24 hours post dose on Days -1, 1, 15 and 16

Secondary Outcome Measures

Outcome Measure	Time Frame
Omerprazole/metoprolol/midazolam - Pharmacokinetic parameter : Cmax, Tmax, and t1/2z	predose and up to 24 hours post dose on Days -1, 1, 15 and 16
SAR302503 - Pharmacokinetic parameter : Cmax, Tmax, Ctrough and AUC0-24	Day-1 to Day 16
Clinical and laboratory events graded by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v4.03 (Segment 1 and 2)	up to maximum 2 years
Objective response ratio (Complete response (CR) and partial response (PR)) (Segment 2)	up to 2 cycles ( i.e. 10 weeks)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: April 13, 2012
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (ESTIMATE): April 26, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 22, 2013
• Last Update Submitted That Met QC Criteria: March 21, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Midazolam; Metoprolol
• Other Study ID Numbers: INT12497; U1111-1125-8930 (OTHER: UTN)