A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01017939
First received: November 19, 2009
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to evaluate the effects of multiple doses of abiraterone acetate plus prednisone on the pharmacokinetics (study of what the body does to a drug) of single doses of dextromethorphan hydrobromide and theophylline in patients with castration resistant prostate cancer.


Condition Intervention Phase
Prostate Neoplasms
Drug: Abiraterone acetate
Drug: Prednisone
Drug: Dextromethorphan hydrobromide
Drug: Theophylline
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Ratio of the mean area under the concentration curve (AUC) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone [ Time Frame: Cycle 1 Day -8 and Day 8 ] [ Designated as safety issue: No ]
  • Ratio of the mean maximum plasma concentration (Cmax) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone [ Time Frame: Cycle 1 Day -8 and Day 8 ] [ Designated as safety issue: No ]
  • Ratio of the mean area under the concentration curve (AUC) of theophylline with and without co-administration of abiraterone acetate and prednisone [ Time Frame: Cycle 1 Day -8 and Day 8 ] [ Designated as safety issue: No ]
  • Ratio of the mean maximum plasma concentration (Cmax) of theophylline with and without co-administration of abiraterone acetate and prednisone [ Time Frame: Cycle 1 Day -8 and Day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants reporting adverse events [ Time Frame: Up to 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Enrollment: 34
Study Start Date: January 2010
Study Completion Date: April 2012
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: abiraterone + prednisone + dextromethorphan
Group A will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP2D6 using 2 single doses of dextromethorphan hydrobromide as a probe drug.
Drug: Abiraterone acetate
Abiraterone acetate 1000 mg tablets administered orally once daily beginning on Cycle 1 Day 1 up to the time of disease progression
Drug: Prednisone
Prednisone 5mg tablets administered orally twice daily beginning on Cycle 1 Day 1 up to the time of disease progression
Drug: Dextromethorphan hydrobromide
Dextromethorphan hydrobromide 30 mg capsules administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions
Experimental: Group B: abiraterone + prednisone + theophylline
Group B will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP1A2 using 2 single doses of theophylline as a probe drug.
Drug: Abiraterone acetate
Abiraterone acetate 1000 mg tablets administered orally once daily beginning on Cycle 1 Day 1 up to the time of disease progression
Drug: Prednisone
Prednisone 5mg tablets administered orally twice daily beginning on Cycle 1 Day 1 up to the time of disease progression
Drug: Theophylline
Theophylline 100 mg tablets administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions

Detailed Description:

This is an open-label (identity of assigned study drug will be known) study of abiraterone acetate plus prednisone in male patients with metastatic castration-resistant prostate cancer. This study will consist of screening, treatment, and follow-up periods, and will have 2 study groups. Patients in Group A and B will receive daily abiraterone acetate (1000 mg) plus prednisone (5 mg) twice daily beginning on Cycle 1 Day 1 until disease progression. Patients in Group A will take dextromethorphan hydrobromide 30 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Patients in Group B will take theophylline 100 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Serial pharmacokinetic samples will be collected and safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
  • Documented metastatic disease
  • Documented prostate specific antigen (PSA) progression according to Prostate Cancer Working Group 2 criteria, with PSA value >=2 ng/mL despite medical or surgical castration, or prostate cancer progression documented by radiographic progression according to Response Evaluation Criteria In Solid Tumors criteria
  • Surgically or medically castrated with testosterone levels of <50 ng/dL
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of <=2
  • Group A only: genomic testing at screening indicating CYP2D6 extensive metabolizer status
  • Protocol-defined laboratory values

Exclusion Criteria:

  • Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
  • Group A only: genomic testing at screening indicating CYP2D6 non-extensive metabolizer status, or prior treatment with dextromethorphan-containing medication or any medication that is a strong inhibitor or inducer of CYP2D6 within 5 half-lives of that drug or 7 days, whichever is longer, prior to Cycle 1 Day -8
  • Group B only: prior treatment with theophylline or any medication that is a strong inhibitor or inducer of CYP1A2 within 5 half-lives of that drug or 7 days, whichever is longer, prior to Cycle 1 Day -8
  • Abnormal liver function
  • Uncontrolled hypertension (repeated systolic blood pressure >=160 mmHg, or diastolic blood pressure >=95 mmHg)
  • Active or symptomatic viral hepatitis or chronic liver disease
  • Known brain metastasis
  • History of pituitary or adrenal dysfunction
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class III or IV heart disease or cardiac ejection fraction measurement of <50% at baseline
  • History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
  • Surgery or local prostatic intervention within 28 days of the first dose, and any clinically relevant sequelae from the surgery must have resolved prior to Cycle 1 Day 1
  • Radiotherapy or immunotherapy within 28 days, or single fraction of palliative radiotherapy within 14 days of administration of Cycle 1 Day 1
  • Any acute toxicities due to prior therapy that have not resolved
  • Current enrollment in an investigational drug or device study or participation in such a study within 28 days of Cycle 1 Day 1
  • Previous abiraterone acetate or other investigational CYP17 inhibitor (eg, TAK-700)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01017939

Locations
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
Beverly Hills, California, United States
United States, Texas
START - South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229
San Antonio, Texas, United States
Canada, British Columbia
BC Cancer Agency
Vancouver, British Columbia, Canada, V5Z 4E6
Vancouver, British Columbia, Canada
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01017939     History of Changes
Other Study ID Numbers: CR017128, COU-AA-015
Study First Received: November 19, 2009
Last Updated: April 11, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Janssen Research & Development, LLC:
Prostate neoplasms
Metastatic castration resistant prostate cancer
Metastatic castration refractory prostate cancer
Prostate cancer
Abiraterone acetate
CB7630

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Dextromethorphan
Theophylline
Prednisone
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Vasodilator Agents
Cardiovascular Agents
Purinergic P1 Receptor Antagonists
Purinergic Antagonists

ClinicalTrials.gov processed this record on August 20, 2014