Clinical trial NCT01897389: A Study to Assess the Relative Bioavailability of 4 New Abiraterone Acetate Tablet Formulations With Respect to the Current Commercial Abiraterone Acetate Tablet Under Fasted Conditions in Healthy Male Participants
Official title: A Single-Dose, Open-Label, Randomized, 4-Period, 5-Treatment Crossover Study to Assess the Relative Bioavailability of 4 New Abiraterone Acetate Tablet Formulations With Respect to the Current Commercial Abiraterone Acetate Tablet Under Fasted Conditions in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Healthy volunteers
Bioavailability
Abiraterone acetate
ZYTIGA
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-07-12
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the relative bioavailability of 4 new formulations of abiraterone acetate compared to the current commercial formulation.

Detailed description: This is a randomized (individuals will be assigned by chance to study treatments), open-label (individuals will know the identity of study treatments), 4-period, 5-treatment crossover study in order to evaluate the relative bioavailability of 4 new formulations of abiraterone acetate compared to the current commercial formulation. Approximately 32 healthy adult males will participate. The total study length is up to 68 days. This study will consist of a screening phase followed by an open-label treatment phase consisting of 4 single-dose treatment periods separated by a washout period of at least 7 days between dosing. Individuals will be randomly assigned to 1 of 8 treatment sequences. A single dose of 1000 mg abiraterone acetate will be given in each treatment period under fasted conditions. Participants will be confined to the study center from Day -1 of each treatment period until completion of the 96-hour blood sample collection on Day 5 of each treatment period. A follow-up visit will occur between 5 to 7 days after the last study procedure. Serial pharmacokinetic (study of what the body does to a drug) samples will be collected during the open-label treatment phase as detailed in the protocol. Safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Agrees to protocol-defined use of effective contraception for up to 1 week after receiving the last dose of study drug and agrees to not donate sperm during the study and for 1 week after receiving the last dose of study drug
* Body mass index between 18.5 and 30.0 kg/m2 (inclusive) and body weight not less than 50 kg
* Blood pressure (after lying down for 5 minutes) between 90 and 140 mmHg systolic and no higher than 90 mmHg diastolic
* A 12-lead electrocardiogram consistent with normal cardiac conduction and function
* Non-smoker and no use of nicotine-containing substances within the previous 2 months
* Laboratory values within protocol-defined parameters

Exclusion Criteria:

* History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the patient or that could interfere with the interpretation of the study results
* Clinically significant abnormal values for hematology, clinical chemistry, urinalysis, or clinically significant abnormal physical examination, vital signs, or 12-lead electrocardiogram at screening or at admission to the study center as deemed appropriate by the investigator
* Screening serum testosterone level of \<200 ng/dL
* Presence of sexual dysfunction or any medical condition that would affect sexual function
* Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, within 14 days before the first dose of the study drug is scheduled through study completion
* History of, or a reason to believe a participant has a history of drug or alcohol abuse within the past 5 years
* Positive test for drugs of abuse (such as cannabinoids, alcohol, opiates, cocaine, amphetamines, benzodiazepines, hallucinogens, or barbiturates) at screening and Day -1 of each treatment period
* Known allergy to the study drug or any of the excipients of the formulation
* History of stomach or intestinal surgery or resection that would potentially alter absorption or excretion of orally administered drugs (appendectomy and hernia repair will be allowed)
* Donated blood or blood products or had substantial loss of blood within 3 months before the first administration of study drug or intention to donate blood or blood products during the study
* Received an experimental drug or used an experimental medical device within 1 month or within a period less than 10 times the drug's half-life, whichever is longer, before the first dose of the study drug is scheduled
* Unable to swallow solid, oral dosage forms whole with the aid of water
* Positive test for human immunodeficiency virus 1 and 2 antibodies, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibodies
* Preplanned surgery or procedures that would interfere with the conduct of the study

Primary outcomes:
measure: Maximum plasma concentration of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
measure: Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
measure: Area under the plasma concentration-time curve from time 0 to infinite time of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
measure: Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
measure: Time to reach the maximum plasma concentration of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
Secondary outcomes:
measure: Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
timeFrame: Up to 30 days after the last dose of study medication
Other outcomes:
measure: Percentage of area under the plasma concentration-time curve from time 0 to infinite time obtained by extrapolation of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
measure: First-order rate constant associated with the terminal portion of the drug-concentration-time curve of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
measure: Time to last quantifiable plasma concentration of abiraterone
timeFrame: Periods 1-4 pharmacokinetic profile from Day 1 predose and postdose at 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 96 h
Locations:
city: Tempe
country: United States
state: Arizona
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: