Phase 1, Open-Label, Single-Ascending Dose, Parallel Group Study to Determine the Pharmacokinetics, Safety, and Tolerability of ATRS-2002 Administered Subcutaneously in Healthy Adult Males
Overview
- Phase
- Phase 1
- Intervention
- Abiraterone Acetate
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Sponsor
- Syneos Health
- Primary Endpoint
- Pharmacokinetic assessment
- Status
- Withdrawn
- Last Updated
- 3 years ago
Overview
Brief Summary
To access the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneously administered ATRA-2002 against commercially available oral formulation of abiraterone acetate in healthy male adults
Detailed Description
The study will be conducted in 4 dosing groups of 8 subjects each. Thirty-two healthy adult men will be randomly assigned to a treatment cohort and will receive either a single Subcutaneous (SC) dose of ATRS-2002 (abiraterone acetate), or a single oral dose of the commercially available formulation of abiraterone acetate (Zytiga®). Additionally, for Cohorts 1 through 3, a single subject will be randomized as a sentinel subject to be dosed at least 24 hours prior to the rest of cohort (ROC). Dosing in the abiraterone acetate SC cohorts will be sequential and will start with subjects in the lowest SC dosing cohort (i.e., 25 mg). Dosing will not begin in the next highest SC dose cohort until all safety data, as well as available PK (Pharmacokinetic) data and TT levels, from the previous cohort(s) have been reviewed by the safety review committee (SRC e.g., Sponsor and Investigator) and it has been deemed safe to proceed to the next highest dose. Dosing in the oral abiraterone acetate cohort (Cohort 4) may begin at any time during the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntarily provide written informed consent for participation in the study.
- •Be a male 18 to 55 years of age, inclusive at the time of consent.
- •Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive at screening.
- •Have a normal electrocardiogram (ECG) at screening.
- •Have normal results for hematology, biochemistry, liver function, lipids and urinalysis tests at screening and at Day -1, as defined by laboratory normal ranges. Subjects with results outside of the normal ranges that are considered to be not of clinical significance may be admitted to the study at the discretion of the Investigator.
- •Have a potassium level greater than or equal to 3.8 mEq/L.
- •Have a testosterone value within the normal range at screening.
- •Have vital signs within the normal range at screening, as defined by site standard ranges. Assessments for vital signs may be repeated up to 3 times, at the discretion of the Investigator.
- •Subjects who are not vasectomized for at least 6 months, and who are sexually active with a female partner of child bearing potential (does not include post menopausal women \[absence of menses for 12 months prior to drug administration\] or women who have had a hysterectomy or bilateral oophorectomy \[at least 6 months prior to drug administration\]) must be willing to use one of the following acceptable contraceptive methods for at least 120 days post-dose:
- •Simultaneous use of a condom and, for the female partner, hormonal contraceptives (used since at least 4 weeks);
Exclusion Criteria
- •Has a known allergy to study drug or any excipients contained within the study drug.
- •Has any acute or active chronic disease. Mild conditions that only require intermittent treatment and are unlikely to interfere with study results may be permitted at the discretion of the Investigator (examples include seasonal hay fever and mild eczema).
- •Has a history of any clinically important cardiovascular, pulmonary, hepatic, renal, dermal, central nervous system (CNS), or neuromuscular disease disorders or asthma (excluding non current, childhood asthma) or diabetes or any other clinically important disorder, as determined by the Investigator.
- •Has a predisposing condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs or any condition that may confound the PK analyses, particularly hepatic or renal disease, as determined by the Investigator.
- •Has a history of anaphylaxis, or other severe reaction, to a drug, food, toxin, or other exposure.
- •Has an elevated PSA level at screening.
- •Has received another investigational drug including investigational agent(s) targeting the androgen receptor within 30 days or 5 half-lives (whichever is longer) prior to the screening visit.
- •Is taking, or has taken, any prescribed or over-the-counter drug or herbal product known to modulate cytochrome P450 (CYP)17 (e.g., ketoconazole, abiraterone acetate, orteronel, galeterone, or seviteronel) in the 30 days prior to the screening visit, or is planning to take any of these medications at any time during the study.
- •Is taking, or has taken, any prescribed or over-the-counter drug, herbal, or food known to modulate CYP3A4 in the 30 days prior to the screening visit, or is planning to take any of these medications or foods at any time during the study.
- •Is taking, or has taken, any prescribed CYP2D6 substrate in the 7 days (or 5 half-lives, whichever is longer) prior to the screening visit, or is planning to take any of these medications or foods at any time during the study.
Arms & Interventions
SC ATRS-2002
3 different dosages \[25mg (0.13mL) , 75mg (0.4mL) and 200mg (1.05mL)\] will be tested as single SC injection into the abdomen.
Intervention: Abiraterone Acetate
Oral Abiraterone Acetate
A single dose of 1000mg of commercially available oral formulation of abiraterone acetate will be administered to enrolled participants in Cohort 4
Intervention: Abiraterone Acetate
Outcomes
Primary Outcomes
Pharmacokinetic assessment
Time Frame: Pre-dose (within 30 minutes), Post dose - 4hours, 8hours, 12hours on day 1 and then 24hours, 36hours, 48hours, 60hours, 72hours, 84hours, 96hours, 168hours, 240hours, 336hours, 504hours, 672hours
Peak concentration (CMAX)
Pharmacodynamic assessment
Time Frame: Pre-dose (within 30 minutes), Post dose - 4hours, 8hours, 12hours on day 1 and then 24hours, 36hours, 48hours, 60hours, 72hours, 84hours, 96hours, 168hours, 240hours, 336hours, 504hours, 672hours
To determine TT (total testosterone) and LH (luteinizing hormone) levels from whole blood
Secondary Outcomes
- Safety assessment(Screening (Days -28 to -2), Day -1, Day 3, Day 5, Day 15, Day 29)
- Local tolerability(Immediately after SC dosing on day 1, 4, 8, 12, 24, 36, 48, 60, 72 and 96 hrs post dose. On day 8-to measure pain 11-point numeric pain rating scale will be used)