The purpose of this study is to assess the single dose pharmacokinetic profile (explores what a drug does to the body) and safety of Osmotic Release Oral System (OROS) hydromorphone in chinese participants with cancer (abnormal tissue that grows and spreads in the body) who are not opioid (morphine-like medications) tolerant (decrease in response to a fixed dosage of drug over time and higher doses of a drug are needed to get desired effect).
This is an open-label (all people know the identity of the intervention), single-dose study in adult chinese participants with cancer. The study will consist of a screening phase (within 21 to 1 days before admission to the research facility on Day -1) followed by a 4-day open-label treatment phase (Day -1 to Day 3). Participants will remain confined to the study center from Day -1 until completion of the end-of-study visit or withdrawal assessments, which will be done upon completion of the 48-hour pharmacokinetic sampling on Day 3, or upon early withdrawal. The total study duration will be approximately 24 days. All participants will undergo a naloxone challenge test (at a subcutaneous \[under the skin\] dose of 0.8 milligram \[mg\]) for opioid dependency during the screening phase. Only those participants who pass this challenge test will be allowed to continue in the study. During the treatment phase, upon completion of a 10-hour overnight fast, participants will receive a single oral (having to do with the mouth) 8 mg dose of hydromorphone in the morning of Day 1. Serial blood samples will be collected immediately before and through 48 hours after dosing for the determination of plasma hydromorphone concentrations. Participants will be administered naltrexone 50 mg, to block the opioid effects of hydromorphone, 14 hours before, 2 hours before, and 10 hours after study drug administration. After the 10-hour dose, additional doses of naltrexone will be administered every 12 hours up to 34 hours postdose. Participants' safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Participants will be administered a single dose of Osmotic Release Oral System (OROS) hydromorphone tablet of 8 milligram (mg) orally on Day 1 under fasting conditions.
Unnamed facility
Beijing, China
Unnamed facility
Changsha, China
Maximum Plasma Concentration (Cmax)
The Cmax is the maximum observed plasma concentration of study drug.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours (AUC[0-48])
The AUC(0-48) is the area under the plasma concentration-time curve from time 0 to 48 hours post-dose.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC[0-last])
The AUC(0-last) is area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
The AUC(0-infinity) is the area under the plasma concentration-time curve from time 0 to extrapolated infinite time, calculated as the sum of AUC(0-last) and C(last)/tau where C(last) is the last observed quantifiable concentration and 'tau' is the first-order rate constant associated with the terminal portion of the curve.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Percentage of AUC Obtained by Extrapolation (%AUC[inf,ex])
Percentage of AUC obtained by extrapolation (%AUC\[inf,ex\]) is calculated by dividing the difference of AUC(0-infinity) and AUC(0-last) by AUC(0-infinity) and then multiplying by 100 (AUC\[0-infinity\] - AUC\[0-last\])\*100/AUC\[0-infinity\].
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
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Enrollment
12
Time to Reach the Maximum Plasma Concentration (tmax)
The tmax is the time to reach the maximum plasma concentration of study drug.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Terminal Elimination Half Life (t1/2)
The t1/2 is the elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve and is calculated as 0.693/tau where tau is the first-order rate constant associated with the terminal portion of the curve.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
First-Order Rate Constant Associated With the Terminal Portion of the Curve
The first-order rate constant associated with the terminal portion of the curve (tau) is determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Apparent Clearance (CL/F)
Apparent Clearance (CL/F) is calculated by dividing the dose by area under the curve from time 0 to 48 hours post-dose (AUC\[0-48\]).
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Apparent Volume of Distribution (Vd/F)
Apparent Volume of Distribution (Vd/F) is calculated by multiplying apparent clearance (CL/F) with the first-order rate constant associated with the terminal portion of the curve (tau).
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose