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Prostate CancerPhase 1NCT04094519

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

A Phase 1 study testing enzalutamide, digoxin and rosuvastatin in people with Prostate Cancer, run by Astellas Pharma Global Development, Inc. at 1 site in Moldova.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
enzalutamide, digoxin and rosuvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteMoldova
Study dates
27 Jan 2020to 27 Dec 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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)
  • Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening
  • Subject has previously received treatment with enzalutamide.
  • Subject has undergone major surgery within 4 weeks prior to day 1.
  • Subject has a known hypersensitivity reaction to enzalutamide, digoxin, rosuvastatin, contrast agents or any of the components of the formulations used.
  • Subject has an absolute neutrophil count < 1500/μL, platelet count < 100000/μL and hemoglobin < 6.2 mmol/L (9 g/dL) during the screening period.
  • Subject has received any growth factors or blood transfusions within 7 days prior to the hematologic laboratory values obtained during the screening period.
  • Subject has a total bilirubin (TBL) > 1.5 times the upper limit of normal (ULN) (except for subjects with documented Gilbert's disease), alanine aminotransferase (ALT) > 2.5 times the ULN or aspartate aminotransferase (AST) > 2.5 times the ULN during the screening period. Subject with alkaline phosphatase (ALP) > 3 times ULN will be excluded, unless deemed to be related to bone metastasis, rather than liver disease, and after discussion with the sponsor's medical monitor.
  • Subject has an albumin < 30 g/L (3.0 g/dL) or creatinine > 177 μmol/L (> 2 mg/dL) during the screening period.
  • Subject has clinical signs and symptoms of hereditary or acquired coagulation disorders within 6 months prior to enrollment (day 1 visit).
  • Subject has a history of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence. The medical monitor and investigator must agree that the possibility of recurrence is remote.
  • Subject received treatment with chemotherapy within 4 weeks prior to enrollment (day 1) or plans to initiate treatment with chemotherapy during the study.
  • Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 28 days or 5 half-lives, whichever is longer, prior to the initiation of screening.
  • Subject has a gastrointestinal disorder affecting absorption.
  • Subject uses concomitant medications that are inducers or inhibitors of P-gp and/or BCRP or strong CYP2C8 inhibitors or strong CYP3A4 inducers.
  • Subject uses digoxin or rosuvastatin or concomitant medications that are contraindicated with digoxin or rosuvastatin.
  • Subject has any history or evidence of any clinically significant gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease.
  • Subject has used drugs of abuse (if not medically indicated) within 3 months prior to admission to the clinical unit.
  • Subject has a history of consuming > 21 units of alcohol per week within 3 months prior to day -1 (note: 1 unit = 10 g pure alcohol, 250 mL of beer [5%], 35 mL of spirits [35%] or 100 mL of wine [12%]) or the subject tests positive for alcohol at screening or on day -1.
  • Subject has known active hepatitis B (hepatitis B surface antigen [HBsAg] reactive, associated with positive anti-hepatitis B core and detectable hepatitis B virus DNA), active hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected) or active viral hepatitis A (immunoglobulin M).
  • Subject has a positive human immunodeficiency virus type 1 and/or type 2 at screening.
  • Subject is an employee of Astellas, the study-related contract research organizations (CRO) or the clinical unit.

Trial locations and contacts

1 site in 1 country.

Moldova1 site

  • Site MD37301

    Chisinau

Other trials in Moldova

About this study

Official title: A Phase 1 Open-label 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

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.

Read the detailed description

Eligible participants will be admitted to the clinical unit on day -1. Participants may be discharged from the clinical unit on day 2 on the condition that all required assessments have been performed and that there are no medical reasons for a longer stay in the clinical unit and participants are able and willing to return to the clinical unit on days 3 to 8 for daily pharmacokinetic sampling. Or, participants may choose to remain in the clinical unit up to the 168 hour postdose (day 8) pharmacokinetic sample collection.

Participants will return to the clinical unit on day 35 for an ambulant visit and will be admitted to the clinical unit on day 63. Participants may be discharged from the clinical unit on day 65 on the condition that all required assessments have been performed and that there are no medical reasons for a longer stay in the clinical unit and participants are able and willing to return to the clinical unit on days 66 to 71 for daily pharmacokinetic sampling. Or, participants may choose to remain in the clinical unit up to the 168 hour postdose (day 71) pharmacokinetic sample collection.

From day 72 onwards, participants experiencing clinical benefit (determined by the investigator in consultation with the physician responsible for treating the participants' prostate cancer) may roll over into an open label, single arm extension study. Only participants who will be enrolled into the extension study will continue to receive enzalutamide until any discontinuation criterion occurs per the extension study protocol.

Conditions
Prostate Cancer
Being tested
enzalutamide, enzalutamide Placebo, digoxin, rosuvastatin
Keywords
ASP9785, enzalutamide, prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04094519
Study groupRoleWhat they receive
digoxin plus rosuvastatin and enzalutamideExperimentalParticipants 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.
Receives: Drug: enzalutamide; Drug: enzalutamide Placebo; Drug: digoxin; Drug: rosuvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: Up to Day 71

  2. 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.

    Measured: Up to Day 71

  3. 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.

    Measured: Up to Day 71

Secondary outcomes (7)

  1. Number of participants with Adverse Events (AEs)

    Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA).

    An AE is any untoward medical occurrence in a participant administered an Investigational Product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of IP whether or not considered related to the IP.

    An AE is considered "serious" if the event: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures)or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); or other medically important events.

    Measured: Up to Day 101

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

    Number of participants with potentially clinically significant laboratory values.

    Measured: Up to Day 101

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

    Number of participants with potentially clinically significant vital sign values.

    Measured: Up to Day 101

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

    Number of participants with potentially clinically significant ECG values.

    Measured: Up to Day 101

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

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

    Measured: Up to Day 71

  6. Pharmacokinetics (PK) of enzalutamide and its metabolite (N-desmethyl) in plasma: area under the concentration-time curve during a dosing interval, where tau (τ) is the length of the dosing interval (AUCtau)

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

    Measured: Up to Day 71

  7. Pharmacokinetics (PK) of enzalutamide and its metabolite (N-desmethyl) in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)

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

    Measured: Up to Day 71

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2019
  2. Study start27 Jan 2020
  3. Primary completion27 Dec 2020
  4. Study completion27 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04094519
Sponsor's protocol ID
9785-CL-0018
Status last verified
Nov 2024
First submitted
17 Sep 2019
Last updated
20 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • 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.

    PubMed 35118821

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing enzalutamide, digoxin and rosuvastatin in people with Prostate Cancer, run by Astellas Pharma Global Development, Inc. at 1 site in Moldova.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Moldova. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics (PK) of Digoxin in combination with rosuvastatin in plasma: maximum concentration (Cmax) (time frame: Up to Day 71). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04094519, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024.

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