Effect of Rifampin on the Pharmacokinetics of Ixabepilone in Patients With Advanced Cancer

NCT00207090 | Completed Phase 1 Results

• 1 other identifier: CA163-102
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test how rifampin affects the removal of BMS-247550 (ixabepilone) from the body.

Conditions

Advanced Solid Tumors; Neoplasms

Outcome Measures

Primary Outcomes (10)

• Maximum Plasma Concentration (Cmax)

  Cmax was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [INF])

  AUC (INF) was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Time Taken for Plasma Concentration to Reduce by 50 Percent or Apparent Terminal Plasma Elimination Half-life (T Half)

  T half was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Mean Residence Time Adjusted for Infusion Time (MRT [INF])

  (MRT \[INF\]) was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Total Body Clearance (CLT)

  CLT was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Volume of Distribution at Steady-state (Vss)

  Vss was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Time to Reach Maximum Observed Concentration (T Max)

  T max was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T])

  AUC (0-T) was obtained directly from the concentration-time data.

  Blood samples were collected on Day 1 (pre-dose, then 1h30, 3h, 3h15, 3h30, 4h, 6h and 8h), Day 2, Day 3, Day 4 and Day 8 during ixabepilone administration and repeated for Cycle 2 (Days 22-25 and 29) during ixabepilone and rifampin co-administration.

• Urine 6B-Hydroxycortisol to Cortisol Ratio on Day -1

  The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1.

  Day -1 (0-8 hours and 8-24 hours), 24 hours before starting of ixabepilone administration.

• Urine 6B-Hydroxycortisol to Cortisol Ratio on Day 22

  The urine 6B-hydroxycortisol to cortisol ratio is a measure of hepatic CYP3A4/3A5 activity, which is a potential marker of the rate of clearance of ixabepilone. The urine 6B-hydroxycortisol to cortisol ratios were calculated on Day -1.

  Day 22 (0-8 hours and 8-24 hours) during ixabepilone and rifampin co-administration.

Secondary Outcomes (8)

• Number of Participants Who Died and Who Experienced Other Serious AEs (SAEs), Grade 3-4 AEs, Drug-related AEs and AEs Leading to Study Drug Discontinuation

  From Day 1 to 30 days after the last dose of study drug.

• Number of Participants With Grade 3-4 Hematology Abnormalities

  Screening, Day 1, Day 8, Day 15, Day 22 and Day 29-36.

• Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Bilirubin, Albumin and Phosphorous

  Screening, Days 1 and 22.

• Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Calcium, Magnesium, Potassium, Sodium, Glucose and Uric Acid.

  Screening, Days 2 and 22.

• Number of Participants With Clinically Meaningful Vital Signs Measures

  From screening to the off treatment visit.

Study Arms (1)

Ixabepilone + rifampin

EXPERIMENTAL

Drug: ixabepilone; Drug: Rifampin

Interventions

ixabepilone DRUG

ixabepilone solution, intravenous, 40 mg/m2, once every 3 weeks until disease progression

Also known as: IXEMPRA®, BMS-247550

Ixabepilone + rifampin

Rifampin DRUG

rifampin tablets, oral, 600 mg once daily, only on Days 15 to 21 of Cycle 1 and Days 1 to 7 of Cycle 2

Ixabepilone + rifampin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Up to three prior chemotherapy regimens
• Measurable or non-measurable disease
• Available for treatment and follow-up

You may not qualify if:

• Neuropathy
• Uncontrolled cardiovascular disease
• Refusal to participate in genetic analysis

Sponsors & Collaborators

• R-Pharm: lead

Study Sites (1)

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

ixabepilone; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 21, 2005
• Study Start: September 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: November 2, 2020
• Results First Posted: October 1, 2010

Record last verified: 2020-10

Locations

US (1)