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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
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
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
Vince and Associates Clinical Research
Overland Park, Kansas, United States
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
Time frame: 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.
Time frame: 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
Time frame: Day -7 through Day 150/End of Study or Early Termination
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).
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
Opioid withdrawal symptoms will be measured by Clinical Opiate Withdrawal Scale (COWS) score.
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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
Opioid withdrawal symptoms will be measured by Visual Analog Scale (VAS) total score.
Time frame: Screening through Day 150/End of Study or Early Termination