A Study Evaluating Enzalutamide Pharmacokinetics and Pharmacodynamics, and Related Changes After Drug Switch

A Clinical Study for Evaluating Enzalutamide Pharmacokinetics and Pharmacodynamics, and Related Changes After Drug Switch in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer

This is a study for evaluating enzalutamide pharmacokinetics and pharmacodynamics, and related changes after drug switch in Chinese patients with metastatic castration-resistant prostate cancer. The study primary objective is to evaluate the pharmacokinetic characteristics of enzalutamide in Chinese patients with mCRPC.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: Enzalutamide; Drug: HC1119

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Changsha, China
    • Medical Ethics Committee of Hunan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Voluntarily participated in the study, with understanding of and will to comply with relevant study procedures and signed informed consent form;
2. Chinese male, ≥ 18 years old;
3. With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma;
4. With evidence of metastatic lesions (such as bone scan and CT/MRI);
5. Patients with relapsed, refractory, or progressive disease despite castration (surgery or chemical) or combined androgen deprivation therapy. (Progressive disease is defined as 1 or more of the following 3 criteria: PSA progression: A minimum of 3 rising PSA values with an interval of at least 1 week between determinations, resulting in a final value higher than 50% of the minimum, with a starting PSA value > 2 ng/ml; Soft tissue disease progression as defined by RECIST 1.1; Bone progression as defined by PCWG2 with 2 or more new lesions on bone scan);
6. Castrate levels of testosterone (< 50 ng/dl) at screening; bilateral orchiectomy or ongoing androgen deprivation therapy with effective GnRH analogues;
7. ECOG performance status ≤1;

8. Laboratory tests must meet the following criteria:

   1. Routine Blood Test: hemoglobin (Hb) ≥ 90g/L (no blood transfusions within 14 days prior to screening); absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelet Count (PLT) ≥ 80 x 109/L;
   2. Blood Biochemistry: creatinine (Cr) ≤ 2 x upper limit of normal (ULN), or Cr > 2 x ULN but the calculated CrCl ≥ 60 ml/min; bilirubin (BIL) ≤2 x ULN; alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5 x ULN (or ≤ 5.0 x ULN for patients with liver metastases);
   3. Coagulation: INR < 1.5.
9. Estimated life expectancy > 6 months.

Exclusion Criteria:

1. Participated in other clinical drug trials within 1 month prior to screening, or the occurrence of toxicity caused by previous treatments that has not been relieved to ≤ Grade 2 toxicity (according to CTCAE 4.03) prior to enrollment;
2. Brain metastases;

3. Subjects are excluded if any of the following conditions are met:

   1. Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer);
   2. History of organ transplants;
   3. Past medical history of seizures, serious CNS diseases, or unexplained coma, family history of seizures, or history of traumatic brain injury;
   4. Uncontrolled hypertension (systolic ≥ 160 mmHg or diastolic ≥ 100 mmHg) or other serious cardiovascular diseases. (Patients with a history of hypertension is eligible if his blood pressure is controlled with antihypertensives);
   5. Significant GI dysfunction which may affect the intake, transport, or absorption of drug (such as inability to swallow, chronic diarrhea, and bowel obstruction, etc.), or patients with complete gastrectomy;
   6. Other uncontrolled clinical diseases, including but not limited to: persistent or active infections.

4. Subjects are excluded if any of the following conditions regarding past or concomitant medication are met:

   1. Medications that lower the seizure threshold must be used during the trial;
   2. Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within 4 weeks prior to screening;
   3. Treatment with ketoconazole within 4 weeks prior to screening;
   4. Previously treated with investigational or approved medications that inhibit testosterone synthesis (such as abiraterone acetate, TAK-683, and TAK-448) or target testosterone receptors (such as SHR3680, proxalutamide, and ARN509), except for bicalutamide and flutamide.
5. Known hypersensitivity to any ingredient of the study drugs (enzalutamide and HC-1119) or similar drugs;
6. HIV seropositive;
7. History of medication or drug abuse;
8. Other conditions that subject is determined by the investigator to be unsuitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: enzalutamide; 160mg	Drug: Enzalutamide; oral
EXPERIMENTAL: HC-1119; To be determined	Drug: HC1119; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum drug concentration(Cmax)	From the first dose of the study drug to 12 weeks after dose
Time of maximum drug concentration(Tmax)	From the first dose of the study drug to 12 weeks after dose
Area under curve from time 0 to 24h (AUC0-24h)	From the first dose of the study drug to 12 weeks after dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum drug concentration(Cmax)		From 13 weeks to 24 weeks after dose
Time of maximum drug concentration(Tmax)		From 13 weeks to 24 weeks after dose
Area under curve from time 0 to 24h (AUC0-24h)		From 13 weeks to 24 weeks after dose
Number of patients with adverse events	Safety measures	From the first dose of the study drug to 24 weeks after dose
Percentage of patients with > 50% decrease in prostate specific antigen (PSA)	Percentage of patients with > 50% decrease in PSA levels from baseline at weeks1,3,5 6, 8, 10, and 12.	From the first dose of the study drug to 12 weeks after dose

Collaborators and Investigators

• Sponsor: Hinova Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 7, 2018
• Primary Completion (ACTUAL): October 24, 2018
• Study Completion (ACTUAL): August 28, 2019

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: December 16, 2018
• First Posted (ACTUAL): December 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: HC-1119-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No