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

NCT01017939 | Completed Phase 1

• 2 other identifiers: CR017128COU-AA-015
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

Prostate Neoplasms

Keywords

Prostate neoplasms; Metastatic castration resistant prostate cancer; Metastatic castration refractory prostate cancer; Prostate cancer; Abiraterone acetate; CB7630

Outcome Measures

Primary Outcomes (4)

• 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

  Cycle 1 Day -8 and Day 8

• Ratio of the mean maximum plasma concentration (Cmax) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone

  Cycle 1 Day -8 and Day 8

• Ratio of the mean area under the concentration curve (AUC) of theophylline with and without co-administration of abiraterone acetate and prednisone

  Cycle 1 Day -8 and Day 8

• Ratio of the mean maximum plasma concentration (Cmax) of theophylline with and without co-administration of abiraterone acetate and prednisone

  Cycle 1 Day -8 and Day 8

Secondary Outcomes (1)

• Number of participants reporting adverse events

  Up to 30 days after the last dose of study drug

Study Arms (2)

Group A: abiraterone + prednisone + dextromethorphan

EXPERIMENTAL

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; Drug: Prednisone; Drug: Dextromethorphan hydrobromide

Group B: abiraterone + prednisone + theophylline

EXPERIMENTAL

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; Drug: Prednisone; Drug: Theophylline

Interventions

Abiraterone acetate DRUG

Abiraterone acetate 1000 mg tablets administered orally once daily beginning on Cycle 1 Day 1 up to the time of disease progression

Group A: abiraterone + prednisone + dextromethorphan; Group B: abiraterone + prednisone + theophylline

Prednisone DRUG

Prednisone 5mg tablets administered orally twice daily beginning on Cycle 1 Day 1 up to the time of disease progression

Group A: abiraterone + prednisone + dextromethorphan; Group B: abiraterone + prednisone + theophylline

Dextromethorphan hydrobromide DRUG

Dextromethorphan hydrobromide 30 mg capsules administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions

Group A: abiraterone + prednisone + dextromethorphan

Theophylline DRUG

Theophylline 100 mg tablets administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions

Group B: abiraterone + prednisone + theophylline

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (6)

Tower Cancer Research Foundation

Beverly Hills, California, 90211, United States

Location

Unknown Facility

Beverly Hills, California, United States

Location

START - South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Unknown Facility

Vancouver, British Columbia, Canada

Location

Related Links

• An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study with Dextromethorphan and Theophylline in Patients with Metastatic Castration-Resistant Prostate Cancer

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; Dextromethorphan; Theophylline

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2009
• First Posted: November 23, 2009
• Study Start: January 1, 2010
• Primary Completion: June 1, 2010
• Study Completion: April 1, 2012
• Last Updated: April 12, 2013

Record last verified: 2013-04

Locations

CA (2); US (4)