A Study to Evaluate the Effect of Multiple Doses of Enzalutamide on the Pharmacokinetics of Substrates of P-glycoprotein (Digoxin) and Breast Cancer Resistant Protein (Rosuvastatin) in Male Subjects With Prostate Cancer

NCT04094519 | Completed Phase 1 FDA Drug

• 1 other identifier: 9785-CL-0018
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to determine the effect of multiple once daily administrations of enzalutamide on the pharmacokinetics of a single dose of digoxin (P-glycoprotein (P-gp) substrate) and rosuvastatin (breast cancer resistant protein (BCRP) substrate) in participants with prostate cancer. This study will also evaluate the safety and tolerability of multiple once daily administrations of enzalutamide alone and in combination with a single dose of digoxin (P-gp substrate) and rosuvastatin (BCRP substrate) in participants with prostate cancer, as well, assess the pharmacokinetics of enzalutamide and its active metabolite.

Conditions

Prostate Cancer

Keywords

ASP9785; enzalutamide; prostate cancer

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics (PK) of Digoxin in combination with rosuvastatin in plasma: maximum concentration (Cmax)

  Cmax will be recorded from the pharmacokinetic (PK) plasma samples collected.

  Up to Day 71

• Pharmacokinetics (PK) of Digoxin in combination with rosuvastatin in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)

  AUClast will be recorded from the pharmacokinetic (PK) plasma samples collected.

  Up to Day 71

• Pharmacokinetics (PK) of Digoxin in combination with rosuvastatin in plasma: area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf)

  AUCinf will be recorded from the pharmacokinetic (PK) plasma samples collected.

  Up to Day 71

Secondary Outcomes (7)

• Number of participants with Adverse Events (AEs)

  Up to Day 101

• Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Up to Day 101

• Number of participants with vital sign abnormalities and /or adverse events (AEs)

  Up to Day 101

• Number of participants with routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)

  Up to Day 101

• Pharmacokinetics (PK) of enzalutamide and its metabolite (N-desmethyl) in plasma: maximum concentration (Cmax)

  Up to Day 71

Study Arms (1)

digoxin plus rosuvastatin and enzalutamide

EXPERIMENTAL

Participants will receive a single oral dose cocktail containing 0.25 mg digoxin and 10 mg rosuvastatin on Day 1 and 64. A single oral dose of placebo to match enzalutamide will be given on Day 1 and 160 mg enzalutamide once daily on Days 8 through 71.

Drug: enzalutamide; Drug: enzalutamide Placebo; Drug: digoxin; Drug: rosuvastatin

Interventions

enzalutamide DRUG

oral

Also known as: ASP9785

digoxin plus rosuvastatin and enzalutamide

enzalutamide Placebo DRUG

oral

digoxin plus rosuvastatin and enzalutamide

digoxin DRUG

oral

digoxin plus rosuvastatin and enzalutamide

rosuvastatin DRUG

oral

digoxin plus rosuvastatin and enzalutamide

Eligibility Criteria

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

You may qualify if:

• Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell or small cell histology.
• Subject has a serum testosterone level \< 1.7 nmol/L (50 ng/dL) during the screening period if under androgen deprivation therapy (ADT).
• Subject has newly diagnosed metastatic prostate cancer or progressive disease on ADT confirmed by prostate-specific antigen (PSA) or imaging. Disease progression at screening is defined as 1 or more of the following 3 criteria:
• PSA progression defined by a minimum of 2 rising PSA levels with an interval of ≥ 1 week between each determination. At least 1 PSA value within the 3 months leading up to the screening period should be ≥ 2μg/L (2 ng/mL).
• Soft tissue disease progression defined by the Response Evaluation Criteria in Solid Tumors, version 1.1 for soft tissue disease.
• Bone disease progression defined by 2 or more new lesions on a bone scan.
• Subject is able to swallow enzalutamide capsules and comply with study requirements.
• Subject has an Eastern Cooperative Oncology Group performance status of 0 to 2.
• Subject with a female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 3 months after final investigational product (IP) administration.
• Subject must not donate sperm during the treatment period and for 3 months after final IP administration.
• Subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 3 months after final IP administration.
• Subject has a body mass index range of 18.5 to 35.0 kg/m2 inclusive. The subject weighs at least 50 kg at screening.
• Subject has an estimated life expectancy of at least 6 months.
• Subject agrees not to participate in another interventional study while receiving IP treatment in the present study/participating in the present study.

You may not qualify if:

• Subject has any condition, which makes the subject unsuitable for study participation or is not likely to complete the study for any reason.
• Subject has known metastases in the liver or any hepatic disorder that could affect drug metabolism deemed clinically significant.
• Subject is self-reported as Asian.
• Subject has known or suspected brain metastasis or active leptomeningeal disease.
• Subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, brain arteriovenous malformation).
• Subject has a history of loss of consciousness or transient ischemic attack within 12 months of day 1.
• Subject has clinical signs suggestive of high or imminent risks for pathological fracture, spinal cord compression and/or cauda equine syndrome.
• Subject has clinically significant cardiovascular disease including the following:
• Myocardial infarction within 6 months before screening
• Unstable angina within 3 months before screening
• New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure, unless a screening echocardiogram or multigated acquisition scan performed within 3 months before screening demonstrates a left ventricular ejection fraction ≥ 45%
• History of clinically significant ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
• History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
• Hypotension as indicated by systolic blood pressure \< 86 mm Hg at screening
• Bradycardia as indicated by a heart rate of ≤ 45 beats per minute on the screening electrocardiogram (ECG)

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Pfizer: collaborator

Study Sites (1)

Site MD37301

Chisinau, Moldova

Location

Related Publications (1)

• Poondru S, Ghicavii V, Khosravan R, Manchandani P, Heo N, Moy S, Wojtkowski T, Patton M, Haas GP. Effect of enzalutamide on PK of P-gp and BCRP substrates in cancer patients: CYP450 induction may not always predict overall effect on transporters. Clin Transl Sci. 2022 May;15(5):1131-1142. doi: 10.1111/cts.13229. Epub 2022 Feb 4.

  PMID: 35118821 DERIVED

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Digoxin; Rosuvastatin Calcium

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)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 19, 2019
• Study Start: January 27, 2020
• Primary Completion: December 27, 2020
• Study Completion: December 27, 2020
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1)