Multiple Dose Pharmacokinetics Depot Buprenorphine in Opioid-Dependent Subjects
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 2/24/2018 |
| Start Date: | October 2012 |
| End Date: | May 2014 |
Open-Label, Multicenter, Multiple Dose Study of Safety, Tolerability, Pharmacokinetics, Efficacy Markers, and Opioid Receptor Availability of Subcutaneous Injections of Depot Buprenorphine in Treatment Seeking Opioid-Dependent Subjects
This is an open-label study in treatment seeking opioid-dependent subjects for safety,
tolerability, pharmacokinetics (PK), efficacy markers, and opioid receptor availability of
subcutaneous injections of depot buprenorphine after induction and stabilization of treatment
seeking subjects onto Subutex.
Subjects were planned to receive 4 subcutaneous (SC) injections of RBP-6000 separated by 28
days (Cohorts 1-5) or 6 SC injections of RBP-6000 separated by 28 days (Cohort 6) after a
13-day induction and dose stabilisation period on SUBUTEX Sublingual (SL) tablet at dose
levels of 8-24 mg.
tolerability, pharmacokinetics (PK), efficacy markers, and opioid receptor availability of
subcutaneous injections of depot buprenorphine after induction and stabilization of treatment
seeking subjects onto Subutex.
Subjects were planned to receive 4 subcutaneous (SC) injections of RBP-6000 separated by 28
days (Cohorts 1-5) or 6 SC injections of RBP-6000 separated by 28 days (Cohort 6) after a
13-day induction and dose stabilisation period on SUBUTEX Sublingual (SL) tablet at dose
levels of 8-24 mg.
- Open-label SUBUTEX Sublingual Tablet Induction and Stabilisation Period After completing
the screening period, subjects entered an open-label SUBUTEX SL tablet induction and
stabilisation period to achieve stable daily doses of 8 mg, 12 mg, 14 mg, 24 mg or 8 -
24 mg (variable) during a 13 day inpatient (Day -14 to Day -1) period.
- Open-label Treatment Phase On Day 1, eligible subjects discontinued use of SUBUTEX SL
tablet and received a subcutaneous (SC) injection of RBP-6000. The dose of RBP-6000
received and the cohort to which a subject was assigned depended upon the SUBUTEX SL
tablet dose on Day -1.
- Injection 1 (Day 1): 3 days inpatient post-dose (Day 1 to Day 3) and outpatient
visits (Day 4 to Day 28); serial pharmacokinetic (PK) samples
- Injection 2 (Day 29): 60-hour inpatient pre-dose and post-dose (Day 28 to Day 31)
and outpatient visits (Day 32 to Day 56); sparse PK samples
- Injection 3 (Day 57): 60-hour inpatient pre-dose and post-dose (Day 56 to Day 59)
and outpatient visits (Day 60 to Day 84); sparse PK samples
- Injection 4 (Day 85): 60-hour inpatient pre-dose and post-dose (Day 84 to Day 87)
and outpatient visits (Day 88 to Day 113 [or Day 112 for Cohort 6]); serial PK
samples
- Cohort 6 ONLY: Injection 5 (Day 113): 60-hour inpatient pre-dose and post-dose (Day
112 to Day 115) and outpatient visits (Day 116 to Day 140); serial PK samples
- Cohort 6 ONLY: Injection 6 (Day 141): 60-hour inpatient pre- and post-dose (Day 140
to Day 143) and outpatient visits (Day 144 to Day 169); serial PK samples
- Safety Follow-up: weekly visits up to 60 days post-Injection 4 (PK Day 114 to Day
141) for subjects in Cohorts 1-5 who did not take part in the positron emission
tomography (PET) imaging sub-study and up to 60 days post-Injection 6 (PK Day 169
to Day 197) for subjects in Cohort 6
The objective of the PET imaging sub-study was to evaluate the relationship between
buprenorphine plasma levels and the ability of the 200 mg and 300 mg doses of RBP-6000 to
reduce mu-opioid receptor availability measured with [11C]carfentanil and positron emission
tomography (PET) scans. This objective was exploratory in nature and results are not reported
as part of these summary results.
the screening period, subjects entered an open-label SUBUTEX SL tablet induction and
stabilisation period to achieve stable daily doses of 8 mg, 12 mg, 14 mg, 24 mg or 8 -
24 mg (variable) during a 13 day inpatient (Day -14 to Day -1) period.
- Open-label Treatment Phase On Day 1, eligible subjects discontinued use of SUBUTEX SL
tablet and received a subcutaneous (SC) injection of RBP-6000. The dose of RBP-6000
received and the cohort to which a subject was assigned depended upon the SUBUTEX SL
tablet dose on Day -1.
- Injection 1 (Day 1): 3 days inpatient post-dose (Day 1 to Day 3) and outpatient
visits (Day 4 to Day 28); serial pharmacokinetic (PK) samples
- Injection 2 (Day 29): 60-hour inpatient pre-dose and post-dose (Day 28 to Day 31)
and outpatient visits (Day 32 to Day 56); sparse PK samples
- Injection 3 (Day 57): 60-hour inpatient pre-dose and post-dose (Day 56 to Day 59)
and outpatient visits (Day 60 to Day 84); sparse PK samples
- Injection 4 (Day 85): 60-hour inpatient pre-dose and post-dose (Day 84 to Day 87)
and outpatient visits (Day 88 to Day 113 [or Day 112 for Cohort 6]); serial PK
samples
- Cohort 6 ONLY: Injection 5 (Day 113): 60-hour inpatient pre-dose and post-dose (Day
112 to Day 115) and outpatient visits (Day 116 to Day 140); serial PK samples
- Cohort 6 ONLY: Injection 6 (Day 141): 60-hour inpatient pre- and post-dose (Day 140
to Day 143) and outpatient visits (Day 144 to Day 169); serial PK samples
- Safety Follow-up: weekly visits up to 60 days post-Injection 4 (PK Day 114 to Day
141) for subjects in Cohorts 1-5 who did not take part in the positron emission
tomography (PET) imaging sub-study and up to 60 days post-Injection 6 (PK Day 169
to Day 197) for subjects in Cohort 6
The objective of the PET imaging sub-study was to evaluate the relationship between
buprenorphine plasma levels and the ability of the 200 mg and 300 mg doses of RBP-6000 to
reduce mu-opioid receptor availability measured with [11C]carfentanil and positron emission
tomography (PET) scans. This objective was exploratory in nature and results are not reported
as part of these summary results.
Inclusion Criteria:
- Male and female subjects
- Agree not to take any buprenorphine products other than those administered for the
current study throughout participation in the study
- Body mass index (BMI) of >18.0 to < 33.0 kg/m
Exclusion Criteria:
- Participants with a current diagnosis requiring chronic opioid treatment
- Participants with a history of risk factors of Torsades de Pointes (e.g., heart
failure, hypokalemia, family history of Long QT Syndrome) or an ECG demonstrating a
Fridericia's corrected QT interval (QTcF) >450 msec in males and QTcF > 470 in females
at screening
- Abuse of buprenorphine or use of buprenorphine within 14 days of informed consent
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