Withdrawal SymptomsPhase 3NCT02391571
A Study to Evaluate Withdrawal Effects Following Dosing of Oxycodone/Naltrexone in Methadone-Maintained Subjects
A Phase 3 study testing Oxycodone/Naltrexone Capsules and Oxycodone in people with Withdrawal Symptoms, run by Elite Laboratories, Inc at 1 site in United States.
Trial summary
This single-center study is a randomized, double-blind, active-controlled, multiple-dose, parallel group study to evaluate the potential withdrawal effects, safety and tolerability, and pharmacokinetic and pharmacodynamic effects of multiple doses of oral intact Oxycodone/Naltrexone capsules compared to oxycodone in… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Withdrawal Symptoms
- What is being tested?
- Oxycodone/Naltrexone Capsules and Oxycodone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Mar 2015
- Phase
- Phase 3
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Healthy male or female subjects 18 to 55 years of age, inclusive.
- Body mass index (BMI) within the range of 18.0 to 35.0 kg/m2, inclusive, and a minimum weight of 50.0 kg.
- Maintained on a stable methadone regimen. Subjects must be receiving a methadone dose of 50 to 150 mg/day at Screening, with dosage variation ≤20% for at least 14 days prior to the Screening visit and who are willing to remain on their dose at Screening and for the duration of the study.
- The study volunteer has been previously exposed to opioids while on methadone maintenance without relapse occurring, or in the opinion of the methadone maintenance program Director or Physician, is not at undue risk of relapse from participation in the clinical study.
Who cannot join
- History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results.
- Clinically significant infection/injury/illness within 1 month prior to Screening.
- Has been diagnosed with cancer within 5 years prior to screening (excluding squamous or basal cell carcinoma of the skin), or has an active malignancy of any type (including squamous or basal cell carcinoma of the skin).
- History of major mental illness that in the opinion of the investigator may affect the ability of the subject to participate in the study. Institutionalized subjects will not be eligible for participation.
- Documented history of a medical condition that, in the opinion of the investigator, would compromise the subject's ability to swallow, absorb, metabolize, or excrete test product, including (but not limited to) intractable nausea and/or vomiting and/or severe gastrointestinal narrowing (pathologic or iatrogenic).
- Documented history of, or currently active, seizure disorder or history of clinically significant head injury or syncope of unknown origin.
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- History of severe allergic reaction (including anaphylaxis) to any substance, or previous status asthmaticus, or food allergies/intolerances/restrictions, or special dietary needs which, in the judgment of the investigator, contraindicates the subject's participation in the study.
- History of allergy or hypersensitivity to oxycodone or related drugs (e.g., other opioids) or naltrexone or related drugs (e.g., other antagonists).
- 13. An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family member defined as a spouse, parent, child or sibling, whether biological or legally adopted.
- A subject who, in the opinion of the investigator or designee, is considered unsuitable or unlikely to comply with the study protocol for any reason.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Multiple-Dose, Parallel Group Study to Evaluate the Potential of Withdrawal Effects Following Administration of Oxycodone/Naltrexone Capsules and Oxycodone in Methadone-Maintained Opioid-Dependent Subjects
This single-center study is a randomized, double-blind, active-controlled, multiple-dose, parallel group study to evaluate the potential withdrawal effects, safety and tolerability, and pharmacokinetic and pharmacodynamic effects of multiple doses of oral intact Oxycodone/Naltrexone capsules compared to oxycodone in methadone-maintained opioid-dependent subjects. The study will consist of a Screening Phase, an inpatient Treatment Phase (including a methadone stabilization period, a placebo administration period, a treatment administration period and a safety/washout period), and a Follow-up Phase.
Read the detailed description
Approximately 34 methadone-maintained opioid-dependent subjects will be enrolled in the study. All subjects will be admitted to the clinical study unit (CSU; Visit 2) for a 15-day (with 14 overnight stays) inpatient Treatment Phase visit. Subjects will first undergo a 3-day methadone stabilization period (Days 1 to 3) in which all subjects' methadone administration time will be gradually shifted to the time of dosing that will be used throughout the Treatment Phase (approximately 8 am daily). Following the methadone dosing-time stabilization period, subjects will begin a 2-day oxycodone placebo administration period. On Day 4 and Day 5, all subjects will receive a total of 3 oxycodone placebo doses, separated by 6 hours each, starting from approximately one hour following methadone dose administration. Placebo will be administered in a single-blind manner. Starting on Day 6, subjects will be randomized in a 2:1 (Oxycodone/Naltrexone or Oxycodone) fashion to receive one of the following treatments in a double-blinded manner:
- Oxycodone/Naltrexone, multiple oral daily dosing for 5 days
- Oxycodone, multiple oral daily dosing for 5 days Subjects will receive one of the above-listed treatments three times daily, beginning approximately 1 hour following methadone dosing and every 6 hours until 3 doses have been administered. Subjects will be dosed in this manner for 5 consecutive days (Days 6 to 10). All subjects will remain confined in the CSU for 4 days after the first of three doses of study drug is administered on Day 10 for the safety/washout period, during which they will continue to be assessed and monitored for withdrawal effects. Subjects will be discharged approximately 96 hours after the first dose of study drug (oxycodone/naltrexone or oxycodone) administered on the morning of Day 10, if medically acceptable according to the investigator or designee. All subjects will receive daily phone calls until the Follow-up Phase during which subjects will be asked about the presence of withdrawal symptoms and any other adverse events (AEs).
On Days 4 to 9, safety, withdrawal, pharmacokinetic and pharmacodynamic assessments will be performed up to 13 hours after the first of the three daily study drug doses is administered. Following Day 10 study drug administration, assessments will be completed until 96 hours after the first of the three daily study drug doses is administered on the morning of Day 10.
The Follow-up Phase will be conducted approximately 10 to 14 days after the last drug administration on Day 10 or after early withdrawal from the study and will include standard safety assessments.
- Conditions
- Withdrawal Symptoms
- Being tested
- Oxycodone/Naltrexone Capsules, Oxycodone, Placebo
- Medical subject headings
- Substance Withdrawal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxycodone/Naltrexone CapsulesDrug
Oxycodone/Naltrexone to be taken with stable dose of Methadone
OxycodoneDrug
Oxycodone to be taken with stable dose of Methadone
PlaceboDrug
2 day placebo run in prior to test and active drug phase of study
| Study group | Role | What they receive |
|---|---|---|
| Oxycodone/Naltrexone | Experimental | Oxycodone/Naltrexone Capsules (over-encapsulated), on days 6-10, every 6 hours (at 09:00, 15:00, 21:00) Receives: Drug: Oxycodone/Naltrexone Capsules |
| Oxycodone | Active comparator | Oxycodone Tablets (Over-encapsulated), on Days 6-10, every 6 hours (at 09:00, 15:00, 21:00) Receives: Drug: Oxycodone |
| Placebo Lead-In | Other | Placebo Lead-In: Placebo Capsules (matching to Active and Experimental) on days 4-5, every 6 hours (at 09:00, 15:00, 21:00) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary: Onset of Withdrawal measured by Subjective Opioid Withdrawal Scale(SOWS)
To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Subjective Opioid Withdrawal Scale(SOWS), a set of 16 questions scored on a scale of 0-4 (not at all to extremely) according to how the subject feels at that moment to the questions asked about withdrawal symptoms. The questions are asked during the placebo period 9 times daily , and daily during treatment administration 9 times a day.
Measured: up to 10 days
Primary: Onset of Withdrawal measured by Clinician-Rated Opioid Withdrawal Scale (COWS)
To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Clinician-Rated Opioid Withdrawal Scale (COWS), a set of 11 questions scored by a trained clinician that best describes the subject's signs or symptoms of withdrawal at that time. Each are rated on the apparent relationship to opiate withdrawal. These are assessed during the placebo period 9 times daily , and daily during treatment administration 9 times a day. A total score is tallied that determines mild, moderate, moderately severe or severe withdrawal.
Measured: up to 10 days
Secondary outcomes (3)
Secondary: Pharmacokinetic Profile of Naltrexone and 6β-Naltrexol in Subjects receiving Oxycodone/Naltrexone
To investigate the multiple dose pharmacokinetics of naltrexone, and 6β-naltrexol following repeated daily administration of Oxycodone/Naltrexone in methadone-maintained opioid dependent subjects. All subjects enrolled will have 3 PK samples taken during the placebo period and 3-13 samples taken during days 6-10 of the study. Samples will also be taken during the wash-out period, 2 on Day 11, then daily through Day 14. T max, Cmax AUC Ctrough and apparent first-order terminal elimination half-life will be calculated as part of the PK profile.
Measured: up to 14 days
Secondary: Subjective Pharmacodynamic Effects through the use of Visual Analog Scales (VAS)
To explore the pharmacodynamic effects of Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone maintained opioid-dependent subjects through the use of Visual Analog Scales (VAS) to rate Bad Effects, Feeling Sick and Any Effects at the moment of the scale being administered, with 0 mm being "Not At All" and 100 mm being "Extremely". These are administered during the placebo period 9 times daily , and daily during treatment administration 9 times a day. Also, the measurement will be taken during the wash-out period daily. All enrolled subjects will have the VAS measurements administered.
Measured: up to 14 days
Secondary: Objective Pharmacodynamic Effects through the use of Pupillometry measurements
To explore the physiological effects of Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone maintained opioid-dependent subjects through the use of Pupillometry measurements. An electronic pupillometry will be used, and every effort will be made to use the same eye for each measurement. Measurements will be taken during the placebo period 9 times daily , and daily during treatment administration 9 times a day. Also, the measurement will be taken daily during the wash-out period. All enrolled subjects will have the pupillometry measurements taken.
Measured: up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2015 (estimated)
- Study startFeb 2015
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Withdrawal SymptomsStudies 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 3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Elite Laboratories, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Debra Kelsh, MD, Principal investigator, Vince and Associates
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02391571
- Sponsor's protocol ID
- ELI-004-2015
- Status last verified
- Aug 2016
- First submitted
- 17 Feb 2015
- Last updated
- 10 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Multiple-Dose, Parallel Group Study to Evaluate the Potential of Withdrawal Effects Following Administration of Oxycodone/Naltrexone Capsules and Oxycodone in Methadone-Maintained Opioid-Dependent Subjects
- ClinicalTrials.gov ID
- NCT02391571
- Acronym / sponsor ID
- ELI-004-2015
- Conditions
- Withdrawal Symptoms
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Elite Laboratories, IncIndustry (pharma, biotech, devices)
- Study start
- Feb 2015
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 18 Mar 2015 (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.
This single-center study is a randomized, double-blind, active-controlled, multiple-dose, parallel group study to evaluate the potential withdrawal effects, safety and tolerability, and pharmacokinetic and pharmacodynamic effects of multiple doses of oral intact Oxycodone/Naltrexone capsules compared to oxycodone in methadone-maintained opioid-dependent subjects. The study will consist of a Screening Phase, an inpatient Treatment Phase (including a methadone stabilization period, a placebo administration period, a treatment administration period and a safety/washout period), and a Follow-up Phase.
Detailed description
Approximately 34 methadone-maintained opioid-dependent subjects will be enrolled in the study. All subjects will be admitted to the clinical study unit (CSU; Visit 2) for a 15-day (with 14 overnight stays) inpatient Treatment Phase visit. Subjects will first undergo a 3-day methadone stabilization period (Days 1 to 3) in which all subjects' methadone administration time will be gradually shifted to the time of dosing that will be used throughout the Treatment Phase (approximately 8 am daily). Following the methadone dosing-time stabilization period, subjects will begin a 2-day oxycodone placebo administration period. On Day 4 and Day 5, all subjects will receive a total of 3 oxycodone placebo doses, separated by 6 hours each, starting from approximately one hour following methadone dose administration. Placebo will be administered in a single-blind manner. Starting on Day 6, subjects will be randomized in a 2:1 (Oxycodone/Naltrexone or Oxycodone) fashion to receive one of the following treatments in a double-blinded manner:
- Oxycodone/Naltrexone, multiple oral daily dosing for 5 days
- Oxycodone, multiple oral daily dosing for 5 days Subjects will receive one of the above-listed treatments three times daily, beginning approximately 1 hour following methadone dosing and every 6 hours until 3 doses have been administered. Subjects will be dosed in this manner for 5 consecutive days (Days 6 to 10). All subjects will remain confined in the CSU for 4 days after the first of three doses of study drug is administered on Day 10 for the safety/washout period, during which they will continue to be assessed and monitored for withdrawal effects. Subjects will be discharged approximately 96 hours after the first dose of study drug (oxycodone/naltrexone or oxycodone) administered on the morning of Day 10, if medically acceptable according to the investigator or designee. All subjects will receive daily phone calls until the Follow-up Phase during which subjects will be asked about the presence of withdrawal symptoms and any other adverse events (AEs).
On Days 4 to 9, safety, withdrawal, pharmacokinetic and pharmacodynamic assessments will be performed up to 13 hours after the first of the three daily study drug doses is administered. Following Day 10 study drug administration, assessments will be completed until 96 hours after the first of the three daily study drug doses is administered on the morning of Day 10.
The Follow-up Phase will be conducted approximately 10 to 14 days after the last drug administration on Day 10 or after early withdrawal from the study and will include standard safety assessments.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Oxycodone/Naltrexone | Experimental | Drug: Oxycodone/Naltrexone CapsulesOxycodone/Naltrexone Capsules (over-encapsulated), on days 6-10, every 6 hours (at 09:00, 15:00, 21:00) |
| Oxycodone | Active comparator | Drug: OxycodoneOxycodone Tablets (Over-encapsulated), on Days 6-10, every 6 hours (at 09:00, 15:00, 21:00) |
| Placebo Lead-In | Other | Drug: PlaceboPlacebo Lead-In: Placebo Capsules (matching to Active and Experimental) on days 4-5, every 6 hours (at 09:00, 15:00, 21:00) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy male or female subjects 18 to 55 years of age, inclusive.
- Body mass index (BMI) within the range of 18.0 to 35.0 kg/m2, inclusive, and a minimum weight of 50.0 kg.
- Maintained on a stable methadone regimen. Subjects must be receiving a methadone dose of 50 to 150 mg/day at Screening, with dosage variation ≤20% for at least 14 days prior to the Screening visit and who are willing to remain on their dose at Screening and for the duration of the study.
- The study volunteer has been previously exposed to opioids while on methadone maintenance without relapse occurring, or in the opinion of the methadone maintenance program Director or Physician, is not at undue risk of relapse from participation in the clinical study.
Key exclusion criteria (10 listed)
- History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results.
- Clinically significant infection/injury/illness within 1 month prior to Screening.
- Has been diagnosed with cancer within 5 years prior to screening (excluding squamous or basal cell carcinoma of the skin), or has an active malignancy of any type (including squamous or basal cell carcinoma of the skin).
- History of major mental illness that in the opinion of the investigator may affect the ability of the subject to participate in the study. Institutionalized subjects will not be eligible for participation.
- Documented history of a medical condition that, in the opinion of the investigator, would compromise the subject's ability to swallow, absorb, metabolize, or excrete test product, including (but not limited to) intractable nausea and/or vomiting and/or severe gastrointestinal narrowing (pathologic or iatrogenic).
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 |
|---|---|---|
| Oxycodone/Naltrexone CapsulesOxycodone/Naltrexone to be taken with stable dose of Methadone | Drug | Oxycodone/Naltrexone |
| OxycodoneOxycodone to be taken with stable dose of Methadone | Drug | Oxycodone |
| Placebo2 day placebo run in prior to test and active drug phase of study | Drug | Placebo Lead-In |
Primary outcome
Primary: Onset of Withdrawal measured by Subjective Opioid Withdrawal Scale(SOWS)
Time frame: up to 10 days
To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Subjective Opioid Withdrawal Scale(SOWS), a set of 16 questions scored on a scale of 0-4 (not at all to extremely) according to how the subject feels at that moment to the questions asked about withdrawal symptoms. The questions are asked during the placebo period 9 times daily , and daily during treatment administration 9 times a day.
Primary: Onset of Withdrawal measured by Clinician-Rated Opioid Withdrawal Scale (COWS)
Time frame: up to 10 days
To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Clinician-Rated Opioid Withdrawal Scale (COWS), a set of 11 questions scored by a trained clinician that best describes the subject's signs or symptoms of withdrawal at that time. Each are rated on the apparent relationship to opiate withdrawal. These are assessed during the placebo period 9 times daily , and daily during treatment administration 9 times a day. A total score is tallied that determines mild, moderate, moderately severe or severe withdrawal.
3 secondary outcomes
Secondary: Pharmacokinetic Profile of Naltrexone and 6β-Naltrexol in Subjects receiving Oxycodone/Naltrexone
Time frame: up to 14 days
Secondary: Subjective Pharmacodynamic Effects through the use of Visual Analog Scales (VAS)
Time frame: up to 14 days
Secondary: Objective Pharmacodynamic Effects through the use of Pupillometry measurements
Time frame: up to 14 days
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 10 Aug 2016.
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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.
Debra Kelsh, MD principal investigator
Vince and Associates
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oxycodone/Naltrexone Capsules and Oxycodone in people with Withdrawal Symptoms, run by Elite Laboratories, Inc at 1 site in United States.
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 4 inclusion and 10 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 10 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Primary: Onset of Withdrawal measured by Subjective Opioid Withdrawal Scale(SOWS) (time frame: up to 10 days). The study lists 2 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 10 Aug 2016.