Opioid Use DisorderPhase 1SADNCT03002961
Single Ascending Dose Study of RBP-6000
A Phase 1 study testing RBP-6000 and Suboxone in people with Opioid Use Disorder, run by Indivior Inc. at 1 site in United States.
Trial summary
A multi-center, open-label, single ascending dose study to enroll opioid dependent treatment-seeking subjects. Subjects to be enrolled into 3 cohorts receiving low, medium and high doses of depot buprenorphine. A fourth cohort will be enrolled to evaluate the PK of RBP-6000 after receiving suboxone tablets for 7 days. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- RBP-6000 and Suboxone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Oct 2013
- 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
- Sex: male and female subjects are eligible for entry.
- Age: ≥ 18 to ≤ 65 years.
- Body mass index (BMI) of ≥ 18.0 to ≤ 33.0 kg/m2
- Female subjects must have a negative pregnancy test. Women of child bearing potential should have been surgically sterile for at least 6 months prior to dosing or must agree to take reasonable precautions during the study to avoid pregnancy by agreeing to remain abstinent or to practice one of the following methods of birth control from study screening through the last study visit: double barrier (e.g., diaphragm with spermicide; condoms with spermicide); intrauterine device (IUD); implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months prior to study dosing; or oral, patch, or injected contraceptives or vaginal hormonal device in use for at least 3 consecutive months prior to study.
- Meet DSM-IV-TR criteria for opioid dependence and are seeking opioid-dependence treatment.
- (Note: Subjects need not to be seeking treatment with methadone but be willing to accept methadone treatment as consequence of the study.)
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- Normal or no clinically significant electrocardiogram (ECG) findings at screening or through predose on Day 1.
- Total bilirubin ≤ 2x the upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 2xULN, aspartate aminotransferase (AST) ≤ 2xULN, serum creatinine ≤ 2xULN, and international normalized ratio (INR) ≤ 2xULN.
- Agree not to take any buprenorphine products other than those administered for the current study (SUBOXONE SL tablets and RBP-6000) throughout participation in the study.
- Willing to cooperate with study procedures and provide written informed consent prior to start of any study procedures.
Who cannot join
- Require ongoing opioid therapy for pain or other chronic medical conditions.
- ECG demonstrating QTc > 450 msec in males and QTc > 470 msec in females at clinic entry or prior to administration of RBP-6000.
- Currently dependent by DSM-IV-TR criteria on any substances other than opioids, caffeine, or nicotine.
- Currently (during past 30 days from the signing of the informed consent document) engaged in opioid agonist, partial agonist, or antagonist treatment; or require on-going prescription or over the counter (OTC) medications that are clinically relevant CYP P450 3A4 inducers or inhibitors (e.g., rifampicin, azole antifungals [e.g., ketoconazole], macrolide antibiotics [e.g., erythromycin]). See Appendix 12 for an excluded medications list.
- Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent.
- Buprenorphine use within 30 days of informed consent.
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- Subjects with a COWS score of < 12 on the day of administration of RBP-6000 (Applicable for subjects in Cohort 1-3 only, subjects for cohort 4 will not be excluded with a COWS score <12).
- Subjects with any history of suicidal ideation within 30 days prior to informed consent or study drug administration as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the C-SSRS completed at the screening visit, or any history of suicide attempts.
- Clinically significant abnormality in past medical history or at the screening physical examination that in the opinion of the PI or Sponsor may place the volunteer at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug, including but is not limited to history or concurrent cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease.
- History or presence of allergic or adverse response (including rash or anaphylaxis) to buprenorphine, naloxone, methadone, or the ATRIGEL Delivery System.
- Donation of> 250 mL of blood or plasma or participation in another clinical trial within 30 days prior to signing of the informed consent document for this study.
- Current use of or positive urine screen at clinic admission for barbiturates, benzodiazepines, buprenorphine, or methadone.
- Serology positive for human immunodeficiency virus (HIV), acute hepatitis B, or acute hepatitis C and subjects positive for both hepatitis B surface antigen (HBsAg) and immunoglobulin M antibodies to hepatitis B core antigen (anti-HBc IgM). (Note: Subjects with asymptomatic hepatitis B or C infection may be enrolled.)
- All herbal supplements, grapefruit and grapefruit juices, and OTC medications. Sponsor may allow exceptions of medicines that are unlikely to impact PK or PD results.
- Subjects who have been previously excluded from participation or previously enrolled into the study or have previously participated in a study with RBP-6000.
- Subjects who are unable, in the opinion of the PI or the medically responsible physician, to comply fully with the study requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
Vince and Associates Clinical Research
Overland Park, Kansas, 66212
About this study
Official title: A Multicenter, Open-Label, Single Ascending-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Depot Buprenorphine (RBP-6000) in Opioid-Dependent Subjects
A multi-center, open-label, single ascending dose study to enroll opioid dependent treatment-seeking subjects. Subjects to be enrolled into 3 cohorts receiving low, medium and high doses of depot buprenorphine. A fourth cohort will be enrolled to evaluate the PK of RBP-6000 after receiving suboxone tablets for 7 days.
Read the detailed description
All subjects will undergo screening period of up to 7 days. Eligible subjects in Cohorts 1-3 will receive RBP-6000 doses on at the conclusion of screening. Subjects in Cohort 4 will receive sublingual (SL) Suboxone for 7 days prior to receiving an injection of RBP-6000.
For all cohorts, subjects will be admitted to the clinic 2 days prior to beginning any dosing, and will remain in the clinic through Day 21. Blood collection for hematology, chemistry and serology analysis will be drawn at screening, and intermittently for safety assessments during the study period. Subjects in Cohorts 1-3 will have a PK sample collected pre-dose and serial PK collection post-dosing. Subjects in Cohort 4 will have daily PK collections while admitted during Suboxone dosing and serially after RBP-6000 administration.
Subjects will return to the clinic for PK sample collection through Day 140 or until buprenorphine concentrations fall below 100 pg/mL. Subjects will return to the clinic for safety assessments through Day 150.
Subjects experiencing signs and symptoms of withdrawal prior to RBP-6000 during the residential phase may receive non-opioid rescue medications. Subjects who experience signs and symptoms of withdrawal may receive hydromorphone beginning on Day 11 if necessary. Methadone dosing can begin, if clinically indicated, on Day 16 only for subjects who have not been administered hydromorphone. Subjects will not be allowed to use buprenorphine at any time during the study.
Subjects will also receive psychosocial and behavioral counseling as specified by the PI. The End of Study visit will occur 1 week after Day 84 or 1 week after the monthly follow-up visits after Day 84, given a subject's buprenorphine plasma concentration has fallen below 100 pg/mL. For subjects with plasma concentrations of buprenorphine above 100 pg/mL at Day 140, Day 150 will be the End of Study visit.
Subjects will not be enrolled into the next cohort until safety data for at least the first 6 subjects has been reviewed.
- Conditions
- Opioid Use Disorder
- Being tested
- RBP-6000, Suboxone
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RBP-6000Drug
Also called atrigel buprenorphine
single dose of RBP-6000, preceded by a pharmacokinetic (PK) sample followed by serial PK samples post-dose. Additionally subjects to remain in the clinic through Day 21 for safety assessments
SuboxoneDrug
RBP-6000 injection after 7 days of SL Suboxone administration. Interventions as above with additional daily PK collections during Suboxone treatment prior to RBP-6000 administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects to receive low dose of RBP-6000 subcutaneously as a single injection Receives: Drug: RBP-6000 |
| Cohort 2 | Experimental | Subjects to receive medium dose of RBP-6000 subcutaneously as a single injection Receives: Drug: RBP-6000 |
| Cohort 3 | Experimental | Subjects to receive high dose of RBP-6000 subcutaneously as a single injection Receives: Drug: RBP-6000 |
| Cohort 4 | Experimental | Subjects would receive medium dose RBP-6000 as a single injection after up to 12 mg daily dosing of sublingual (SL) suboxone tablets for 7 days Receives: Drug: RBP-6000; Drug: Suboxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety will be assessed by the frequency of adverse events (AEs), serious AEs, and discontinuations due to AEs (safety and tolerability) in subjects receiving a single dose of RBP-6000.
Safety will be assessed by AEs, ECGs, laboratory measurements, local injection site tolerability and vital signs
Measured: Baseline (defined as last non-missing value prior to dosing) to end of study/day 150 or early termination
Individual, mean and median PK concentrations over time profiles will be plotted for subjects receiving a single dose of RBP-6000 with an adequate number of PK samples collected to derive PK parameters.
Individual plasma concentrations will be collected to compute PK parameters. The individual concentrations will be summarized using descriptive statistics.
Measured: PK prior to injection through Day 150/End of Study or Early Termination
The safety of RBP-6000 when administered as a single SC injection after daily dosing of SL Suboxone will be assessed as a measure of the occurrence of AEs, serious AEs and discontinuations due to AEs
Safety to be assessed by AEs, ECGs, laboratory measurements, local injection site tolerability and vital signs
Measured: Day -7 through Day 150/End of Study or Early Termination
Secondary outcomes (3)
Change from baseline of subject suicidal ideation will be reported using the Columbia Suicide Severity Rating Scale (C-SSRS)
Suicidal ideation scores will be reported using the Columbia Suicide Severity Rating Scale (C-SSRS).
Measured: Screening through Day 150/End of Study or Early Termination
Change from baseline of physician reported withdrawal symptoms will be reported by Clinical Opiate Withdrawal Scale (COWS) score
Opioid withdrawal symptoms will be measured by Clinical Opiate Withdrawal Scale (COWS) score.
Measured: Screening through Day 150/End of Study or Early Termination
Change from baseline of subject reported withdrawal symptoms will be reported by Visual Analog Scale (VAS) total score
Opioid withdrawal symptoms will be measured by Visual Analog Scale (VAS) total score.
Measured: Screening through Day 150/End of Study or Early Termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2016 (estimated)
- Study startJul 2012
- Primary completionFeb 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Use DisorderStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indivior Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03002961
- Sponsor's protocol ID
- RB-US-11-0020
- Acronym
- SAD
- Status last verified
- Dec 2016
- First submitted
- 15 Dec 2016
- Last updated
- 26 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Single Ascending-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Depot Buprenorphine (RBP-6000) in Opioid-Dependent Subjects
- ClinicalTrials.gov ID
- NCT03002961
- Acronym / sponsor ID
- SAD / RB-US-11-0020
- Conditions
- Opioid Use Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Indivior Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Feb 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 26 Dec 2016 (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.
A multi-center, open-label, single ascending dose study to enroll opioid dependent treatment-seeking subjects. Subjects to be enrolled into 3 cohorts receiving low, medium and high doses of depot buprenorphine. A fourth cohort will be enrolled to evaluate the PK of RBP-6000 after receiving suboxone tablets for 7 days.
Detailed description
All subjects will undergo screening period of up to 7 days. Eligible subjects in Cohorts 1-3 will receive RBP-6000 doses on at the conclusion of screening. Subjects in Cohort 4 will receive sublingual (SL) Suboxone for 7 days prior to receiving an injection of RBP-6000.
For all cohorts, subjects will be admitted to the clinic 2 days prior to beginning any dosing, and will remain in the clinic through Day 21. Blood collection for hematology, chemistry and serology analysis will be drawn at screening, and intermittently for safety assessments during the study period. Subjects in Cohorts 1-3 will have a PK sample collected pre-dose and serial PK collection post-dosing. Subjects in Cohort 4 will have daily PK collections while admitted during Suboxone dosing and serially after RBP-6000 administration.
Subjects will return to the clinic for PK sample collection through Day 140 or until buprenorphine concentrations fall below 100 pg/mL. Subjects will return to the clinic for safety assessments through Day 150.
Subjects experiencing signs and symptoms of withdrawal prior to RBP-6000 during the residential phase may receive non-opioid rescue medications. Subjects who experience signs and symptoms of withdrawal may receive hydromorphone beginning on Day 11 if necessary. Methadone dosing can begin, if clinically indicated, on Day 16 only for subjects who have not been administered hydromorphone. Subjects will not be allowed to use buprenorphine at any time during the study.
Subjects will also receive psychosocial and behavioral counseling as specified by the PI. The End of Study visit will occur 1 week after Day 84 or 1 week after the monthly follow-up visits after Day 84, given a subject's buprenorphine plasma concentration has fallen below 100 pg/mL. For subjects with plasma concentrations of buprenorphine above 100 pg/mL at Day 140, Day 150 will be the End of Study visit.
Subjects will not be enrolled into the next cohort until safety data for at least the first 6 subjects has been reviewed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: RBP-6000Subjects to receive low dose of RBP-6000 subcutaneously as a single injection |
| Cohort 2 | Experimental | Drug: RBP-6000Subjects to receive medium dose of RBP-6000 subcutaneously as a single injection |
| Cohort 3 | Experimental | Drug: RBP-6000Subjects to receive high dose of RBP-6000 subcutaneously as a single injection |
| Cohort 4 | Experimental | Drug: RBP-6000, Drug: SuboxoneSubjects would receive medium dose RBP-6000 as a single injection after up to 12 mg daily dosing of sublingual (SL) suboxone tablets for 7 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Sex: male and female subjects are eligible for entry.
- Age: ≥ 18 to ≤ 65 years.
- Body mass index (BMI) of ≥ 18.0 to ≤ 33.0 kg/m2
- Female subjects must have a negative pregnancy test. Women of child bearing potential should have been surgically sterile for at least 6 months prior to dosing or must agree to take reasonable precautions during the study to avoid pregnancy by agreeing to remain abstinent or to practice one of the following methods of birth control from study screening through the last study visit: double barrier (e.g., diaphragm with spermicide; condoms with spermicide); intrauterine device (IUD); implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months prior to study dosing; or oral, patch, or injected contraceptives or vaginal hormonal device in use for at least 3 consecutive months prior to study.
- Meet DSM-IV-TR criteria for opioid dependence and are seeking opioid-dependence treatment.
Key exclusion criteria (16 listed)
- Require ongoing opioid therapy for pain or other chronic medical conditions.
- ECG demonstrating QTc > 450 msec in males and QTc > 470 msec in females at clinic entry or prior to administration of RBP-6000.
- Currently dependent by DSM-IV-TR criteria on any substances other than opioids, caffeine, or nicotine.
- Currently (during past 30 days from the signing of the informed consent document) engaged in opioid agonist, partial agonist, or antagonist treatment; or require on-going prescription or over the counter (OTC) medications that are clinically relevant CYP P450 3A4 inducers or inhibitors (e.g., rifampicin, azole antifungals [e.g., ketoconazole], macrolide antibiotics [e.g., erythromycin]). See Appendix 12 for an excluded medications list.
- Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent.
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 |
|---|---|---|
| RBP-6000Also: atrigel buprenorphinesingle dose of RBP-6000, preceded by a pharmacokinetic (PK) sample followed by serial PK samples post-dose. Additionally subjects to remain in the clinic through Day 21 for safety assessments | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| SuboxoneRBP-6000 injection after 7 days of SL Suboxone administration. Interventions as above with additional daily PK collections during Suboxone treatment prior to RBP-6000 administration | Drug | Cohort 4 |
Primary outcome
Safety will be assessed by the frequency of adverse events (AEs), serious AEs, and discontinuations due to AEs (safety and tolerability) in subjects receiving a single dose of RBP-6000.
Time frame: Baseline (defined as last non-missing value prior to dosing) to end of study/day 150 or early termination
Safety will be assessed by AEs, ECGs, laboratory measurements, local injection site tolerability and vital signs
Individual, mean and median PK concentrations over time profiles will be plotted for subjects receiving a single dose of RBP-6000 with an adequate number of PK samples collected to derive PK parameters.
Time frame: PK prior to injection through Day 150/End of Study or Early Termination
Individual plasma concentrations will be collected to compute PK parameters. The individual concentrations will be summarized using descriptive statistics.
The safety of RBP-6000 when administered as a single SC injection after daily dosing of SL Suboxone will be assessed as a measure of the occurrence of AEs, serious AEs and discontinuations due to AEs
Time frame: Day -7 through Day 150/End of Study or Early Termination
Safety to be assessed by AEs, ECGs, laboratory measurements, local injection site tolerability and vital signs
3 secondary outcomes
Change from baseline of subject suicidal ideation will be reported using the Columbia Suicide Severity Rating Scale (C-SSRS)
Time frame: Screening through Day 150/End of Study or Early Termination
Change from baseline of physician reported withdrawal symptoms will be reported by Clinical Opiate Withdrawal Scale (COWS) score
Time frame: Screening through Day 150/End of Study or Early Termination
Change from baseline of subject reported withdrawal symptoms will be reported by Visual Analog Scale (VAS) total score
Time frame: Screening through Day 150/End of Study or Early Termination
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 26 Dec 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RBP-6000 and Suboxone in people with Opioid Use Disorder, run by Indivior 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 10 inclusion and 16 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 26 Dec 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 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?
Safety will be assessed by the frequency of adverse events (AEs), serious AEs, and discontinuations due to AEs (safety and tolerability) in subjects receiving a single dose of RBP-6000. (time frame: Baseline (defined as last non-missing value prior to dosing) to end of study/day 150 or early termination). The study lists 3 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 26 Dec 2016.