PainPhase 1NCT01824524
A Pharmacokinetic and Safety Study of Osmotic Release Oral System (OROS) Hydromorphone in Non-Opioid Tolerant Chinese Participants With Cancer
A Phase 1 study testing Hydromorphone in people with Pain, run by Xian-Janssen Pharmaceutical Ltd. at 2 sites in China.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pain
- What is being tested?
- Hydromorphone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesChina
- Study dates
- Dec 2011to Aug 2012
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants diagnosed with early stage cancer, with no active metastases (spread of cancer cells from one part of the body to another), or severe intercurrent systemic disease. No extensive radiotherapy (treatment of cancer using x-rays), systemic biologic or cytotoxic therapy within 4 weeks before the first dose of study drug. Immunotherapy (giving of drugs to help the body's immune [protective] system; usually used to destroy cancer cells) or hormone therapy with stable dose would still be allowed
- Participants who are not opioid (morphine-like medications) tolerant: no previous use of an opioid or no use of an opioid within 21 days before the first dose of study drug on Day 1
- Participants who previously have received opioid medication for pain management will have had their opioid medication discontinued for reasons unrelated to this study
- Women must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile, abstinent (not having sexual intercourse), or, if sexually active, be practicing an effective method of birth control before entry, throughout the study and up to 15 days after the end of the study/early withdrawal
- Men must agree to use an adequate contraception method (example, vasectomy [surgery to cut out part or all of the ductus deferens to make a man not able to produce children], double-barrier [using two forms of effective contraception (example, condom and spermicide)], partner using effective contraception) and to not donate sperm during the study and for up to 1 month after the end of the study or early withdrawal
- Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
Who cannot join
- Participants with a history of cardiac, nervous system or respiratory disease which in the investigator's judgment precluded participation in the study because of the potential for respiratory depression
- Participants with gastrointestinal disease of sufficient severity (very serious, life threatening) to be likely to interfere with oral analgesia (drug used to control pain) including: dysphagia (trouble swallowing), vomiting, no bowel (the intestine) movement or bowel obstruction (block, blockage) due to impaction within 5 days of the study, severe gut narrowing that may affect the absorption (the way a drug or other substance enters the body) of orally administered drugs, particularly the insoluble hydromorphone outer coating
- Participants who are unable to swallow solid, oral dosage forms whole with the aid of water
- Use of monoamine oxidase inhibitors (MAO-I) within 21 days before the first dose of study drug on Day 1
- Use of opioids within 21 days before the first dose of study drug on Day 1
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: An Open-Label Study to Evaluate the Single Dose Pharmacokinetic Profile and Safety of OROS® Hydromorphone in Chinese Subjects With Cancer Who Are Not Opioid Tolerant
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).
Read the detailed description
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.
- Conditions
- Pain
- Being tested
- Hydromorphone
- Keywords
- Pain, Hydromorphone, OROS
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydromorphoneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| OROS Hydromorphone | Experimental | Not described Receives: Drug: Hydromorphone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax)
The Cmax is the maximum observed plasma concentration of study drug.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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].
Measured: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Secondary outcomes (5)
Time to Reach the Maximum Plasma Concentration (tmax)
The tmax is the time to reach the maximum plasma concentration of study drug.
Measured: 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.
Measured: 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.
Measured: 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]).
Measured: 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).
Measured: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2013 (estimated)
- Study startDec 2011
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xian-Janssen Pharmaceutical Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xian-Janssen Pharmaceutical Ltd. Clinical Trial, Study director, Xian-Janssen Pharmaceutical Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01824524
- Sponsor's protocol ID
- CR018070
- Other IDs
- 42801PAI1012
- Status last verified
- Aug 2014
- First submitted
- 1 Apr 2013
- Last updated
- 15 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Evaluate the Single Dose Pharmacokinetic Profile and Safety of OROS® Hydromorphone in Chinese Subjects With Cancer Who Are Not Opioid Tolerant
- ClinicalTrials.gov ID
- NCT01824524
- Acronym / sponsor ID
- CR018070
- Conditions
- Pain
- Keywords
- Pain, Hydromorphone, OROS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Xian-Janssen Pharmaceutical Ltd.Industry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 4 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OROS Hydromorphone | Experimental | Drug: Hydromorphone |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participants diagnosed with early stage cancer, with no active metastases (spread of cancer cells from one part of the body to another), or severe intercurrent systemic disease. No extensive radiotherapy (treatment of cancer using x-rays), systemic biologic or cytotoxic therapy within 4 weeks before the first dose of study drug. Immunotherapy (giving of drugs to help the body's immune [protective] system; usually used to destroy cancer cells) or hormone therapy with stable dose would still be allowed
- Participants who are not opioid (morphine-like medications) tolerant: no previous use of an opioid or no use of an opioid within 21 days before the first dose of study drug on Day 1
- Participants who previously have received opioid medication for pain management will have had their opioid medication discontinued for reasons unrelated to this study
- Women must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile, abstinent (not having sexual intercourse), or, if sexually active, be practicing an effective method of birth control before entry, throughout the study and up to 15 days after the end of the study/early withdrawal
- Men must agree to use an adequate contraception method (example, vasectomy [surgery to cut out part or all of the ductus deferens to make a man not able to produce children], double-barrier [using two forms of effective contraception (example, condom and spermicide)], partner using effective contraception) and to not donate sperm during the study and for up to 1 month after the end of the study or early withdrawal
Key exclusion criteria (5 listed)
- Participants with a history of cardiac, nervous system or respiratory disease which in the investigator's judgment precluded participation in the study because of the potential for respiratory depression
- Participants with gastrointestinal disease of sufficient severity (very serious, life threatening) to be likely to interfere with oral analgesia (drug used to control pain) including: dysphagia (trouble swallowing), vomiting, no bowel (the intestine) movement or bowel obstruction (block, blockage) due to impaction within 5 days of the study, severe gut narrowing that may affect the absorption (the way a drug or other substance enters the body) of orally administered drugs, particularly the insoluble hydromorphone outer coating
- Participants who are unable to swallow solid, oral dosage forms whole with the aid of water
- Use of monoamine oxidase inhibitors (MAO-I) within 21 days before the first dose of study drug on Day 1
- Use of opioids within 21 days before the first dose of study drug on Day 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydromorphoneParticipants 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. | Drug | OROS Hydromorphone |
Primary outcome
Maximum Plasma Concentration (Cmax)
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
The Cmax is the maximum observed plasma concentration of study drug.
Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours (AUC[0-48])
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
The AUC(0-48) is the area under the plasma concentration-time curve from time 0 to 48 hours post-dose.
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC[0-last])
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
The AUC(0-last) is area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
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.
Percentage of AUC Obtained by Extrapolation (%AUC[inf,ex])
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]) 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].
5 secondary outcomes
Time to Reach the Maximum Plasma Concentration (tmax)
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)
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
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)
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)
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2014.
- An Open-Label Study to Evaluate the Single Dose Pharmacokinetic Profile and Safety of OROS® Hydromorphone in Chinese Subjects With Cancer who are not Opioid TolerantLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xian-Janssen Pharmaceutical Ltd. Clinical Trial study director
Xian-Janssen Pharmaceutical Ltd.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hydromorphone in people with Pain, run by Xian-Janssen Pharmaceutical Ltd. at 2 sites in China.
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 6 inclusion and 5 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 15 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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?
Maximum Plasma Concentration (Cmax) (time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours post-dose). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Aug 2014.