Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication SUBLOCADE is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. SUBLOCADE should be used as part of a complete treatment plan that includes counseling and psychosocial support. FDA label
Also known as atrigel buprenorphine, extended-release buprenorphine, buprenorphine, SUBLOCADE, Subcutaneous buprenorphine
RBP-6000 · 6 trials · 5 indications
TEAE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= a marked limitation in activity. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical or surgical intervention to prevent one of the outcomes listed in this definition.
Vital signs include: * systolic blood pressure (mmHg) * diastolic blood pressure (mmHg) * respiratory rate (breaths/minute) * pulse oximetry (%) * pulse rate (beats/min) * temperature (C)
TEAE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. The number of participants with TEAEs specific to laboratory tests are summarized.
Data represent the count of participants at various percentage abstinence levels. Abstinence was defined as urine samples being negative for opioids AND negative self-reports (obtained from Timeline Followback (TLFB) interviews) for illicit opioid use. The primary endpoint was based on visits in which paired urine samples and self-reports were expected for each subject as specified in the schedule of events. Missing urine drug screen(s) (UDS) samples and/or self-reports were considered as non-negative.
TEAE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= a marked limitation in activity. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent one of the outcomes listed in this definition. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following outcomes: death; lifethreatening AE; hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacit
% Fluctuation was defined as the degree of fluctuation of buprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cavg\*100, expressed as a percentage. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Cavg = average plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
AUC calculated using the linear trapezoidal rule and requiring a minimum of 5 data points for each time range. Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) at hours 0-24, hours 0-672 The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Cavg was defined as the AUC (timeframe)/timeframe. For example, the sublingual steady-state Cavg reading on Day -1 = AUC0-24/ 24 hours Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Maximum observed plasma concentration, determined directly from individual concentration time data. Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Minimum observed plasma concentration, determined directly from individual concentration time data. Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
The swing of buprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cmin within the dosing interval. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) at hours 0-24, hours 0-672 The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Accumulation index in terms of AUC calculated as ratio of AUCtau Injection 4/ AUCtau Injection 1. AUCtau = area under plasma concentration time curve over the dosing interval tau (for SC RBP-6000, tau=28 days).
Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.
Apparent clearance at steady-state (CLss/F) = Dose / AUCtau (tau was 28 days).
Area under plasma concentration time curve from time zero of Injection 4 extrapolated to infinity; calculated for Injection 4 (last injection) in subjects not participating in PET imaging sub-study only as: (AUC0-∞ was reported if the coefficient of determination R2 was at least 0.8 and the extrapolated area is less than 25%). A minimum of 5 data points was required. AUC up to the last measurable concentration (AUClast) was calculated by using the linear trapezoidal rule.
The terminal phase half life calculated for Injection 4 in subjects not participating in PET imaging sub-study. The t1/2 was reported only if the coefficient of determination R2 was at least 0.8.
% Fluctuation was defined as the degree of fluctuation of norbuprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cavg\*100, expressed as a percentage. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Cavg = average plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
AUC calculated using the linear trapezoidal rule and requiring a minimum of 5 data points for each time range. Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) at hours 0-24, hours 0-672 The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Cavg was defined as the AUC (timeframe)/timeframe. For example, the sublingual steady-state Cavg reading on Day -1 = AUC0-24/ 24 hours Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Maximum observed plasma concentration, determined directly from individual concentration time data. Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Minimum observed plasma concentration, determined directly from individual concentration time data. Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
The swing of norbuprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cmin within the dosing interval. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) at hours 0-24, hours 0-672 The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6
Accumulation index in terms of AUC calculated as ratio of AUCtau Injection 4/ AUCtau Injection 1. AUCtau = area under plasma concentration time curve over the dosing interval tau (for SC RBP-6000, tau=28 days).
Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.
Area under plasma concentration time curve from time zero of Injection 4 extrapolated to infinity; calculated for Injection 4 and 6 (last injection) in subjects not participating in PET imaging sub-study only as: (AUC0-∞ was reported if the coefficient of determination R2 was at least 0.8 and the extrapolated area is less than 25%). A minimum of 5 data points was required. AUC up to the last measurable concentration (AUClast) was calculated by using the linear trapezoidal rule.
The terminal phase half life calculated for Injection 4 in subjects not participating in PET imaging sub-study. The t1/2 was reported only if the coefficient of determination R2 was at least 0.8.
Relative bioavailability will be assessed using AUC0-28days.
Relative bioavailability will also be assessed using Cmax
Safety will be assessed by AEs, ECGs, laboratory measurements, local injection site tolerability and vital signs
Individual plasma concentrations will be collected to compute PK parameters. The individual concentrations will be summarized using descriptive statistics.
Safety to be assessed by AEs, ECGs, laboratory measurements, local injection site tolerability and vital signs
The frequency of all adverse events (AE) and serious adverse events (SAE) deemed to be related to treatment.
| Arm | Type | Description |
|---|---|---|
| RBP-6000 (100/300 mg Flex) | EXPERIMENTAL | On Day 1 of the study all eligible subjects received a single subcutaneous (SC) injection of RBP-6000. Participants returned to the site for monthly injection visits every 28 days (-2/+7 days) for a total of up to 6 injections. Participants were not required to complete all 6 injections and could choose to terminate from the study at any time. For each injection, participants could receive either a dose of 100 mg RBP-6000 or 300 mg RBP-6000, based on the medical judgement of the investigator. |
| RBP-6000 300mg/100mg | EXPERIMENTAL | During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 are separated by 28 days (Day 57-Day 141) and contain RBP-6000 100 mg. In addition, participants received individual drug counseling (IDC) at least once a week. |
| RBP-6000 300mg/300mg | EXPERIMENTAL | During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. In addition, participants received individual drug counseling (IDC) at least once a week. |
| Placebo Matching 300 mg/100 mg RBP-6000 | PLACEBO_COMPARATOR | During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given placebo injections on Days 1 and 29 (matching the RBP-6000 300 mg dose volume). Injections 3-6 are separated by 28 days (Day 57-Day 141) and also contain placebo (matching the RBP-6000 100 mg volume). In addition, participants received individual drug counseling (IDC) at least once a week. |
| Placebo Matching 300 mg RBP-6000 | PLACEBO_COMPARATOR | During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given six placebo injections (volume-matched to RBP-6000 300 mg dose) on Days 1 to 141 with injections separated by 28 days. In addition, participants received individual drug counseling (IDC) at least once a week. |
| (8 mg) RBP-6000: 50 mg | EXPERIMENTAL | Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals. |
| (12 mg) RBP-6000: 100 mg | EXPERIMENTAL | Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals |
| (24 mg) RBP-6000: 200 mg | EXPERIMENTAL | Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who receive RBP-6000 containing 200 mg buprenorphine and reach Day 112 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection. |
| (8 mg) RBP-6000: 100 mg | EXPERIMENTAL | Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals. |
| (14 mg) RBP-6000: 200 mg | EXPERIMENTAL | Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who receive RBP-6000 containing 200 mg buprenorphine and reach Day 112 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection. |
| (8-24 mg) RBP-6000: 300 mg | EXPERIMENTAL | Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. |
| RBP-6000 - Light MW | EXPERIMENTAL | Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a light molecular weight (MW) polymer. |
| RBP-6000 - Heavy MW | EXPERIMENTAL | Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a heavy molecular weight (MW) polymer. |
| RBP-6000 - Intermediate MW | ACTIVE_COMPARATOR | Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with an intermediate molecular weight (MW) polymer (reference). |
| Cohort 1 | EXPERIMENTAL | Subjects to receive low dose of RBP-6000 subcutaneously as a single injection |
| Cohort 2 | EXPERIMENTAL | Subjects to receive medium dose of RBP-6000 subcutaneously as a single injection |
| Cohort 3 | EXPERIMENTAL | Subjects to receive high dose of RBP-6000 subcutaneously as a single injection |
| 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 |
| RBP-6000 | EXPERIMENTAL | A single dose of RBP-6000 will be administered on Study Day 1 |
| Name | Type | Description |
|---|---|---|
| RBP-6000 | DRUG | Monthly injections subcutaneously on alternate sides of participant's abdomen. Dose could be adjusted from 100 mg to 300 mg (or the reverse) based on the medical judgment of the investigator. |
| SUBOXONE | DRUG | SUBOXONE (buprenorphine sublingual film) is used for induction therapy. Participants take sublingual film for 3 days according to the sublingual film prescribing information; they then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to randomization. Following randomization, SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. |
| Placebo | DRUG | Six injections of placebo administered subcutaneously every 28 days on alternate sides of participant's abdomen at volumes matching the experimental drug. |
| Subutex | DRUG | Participants were inducted and stabilized over a 14-day period (study days -14 to -1) on SUBUTEX sublingual tablets. Tablets are placed under the tongue until dissolved. |
| SUBOXONE Sublingual Film | DRUG | Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1. |
Inclusion Criteria: 1. Provide written consent to participate in this study. 2. Completed the End of Study Visit for the RB-US-13-0003 study (NCT02510014). 3. Be considered eligible in the medical judgment of the Investigator. 4. Females: Women of childbearing potential (defined as all women who ar...
RBP-6000 is an investigational small-molecule product developed by Supernus Pharmaceuticals for opioid use disorder and opioid-related disorders. It has been studied in clinical trials that enrolled adults with opioid use disorder in the United States. It is in Phase 2 development overall, and its completed trials span Phase 1 and Phase 3.
RBP-6000 is being developed for the treatment of opioid use disorder and opioid-related disorders. Its clinical trials enrolled treatment-seeking adults with opioid use disorder, including studies of single ascending doses and a depot formulation. It remains investigational and is not described as an approved therapy.
RBP-6000 is developed by Supernus Pharmaceuticals, Inc., which trades under the ticker SUPN. The company is listed as the developer of the asset, and all four of its clinical trials were conducted in the United States.
RBP-6000 is in Phase 2 development. Its clinical program includes four completed trials: three Phase 1 studies and one Phase 3 open-label treatment extension study. No trials are currently active, and all 321 enrolled participants were in completed studies.
RBP-6000 has been studied in four completed trials: NCT03002961, a Phase 1 single ascending dose study; NCT02896296, a Phase 3 open-label treatment extension; NCT02765867, a Phase 1 single-dose study in opioid dependent individuals; and NCT02559973, a Phase 1 pharmacokinetics, safety, and tolerability study of depot buprenorphine.
Across its four completed clinical trials, RBP-6000 has enrolled a total of 321 participants. Enrollment ranged from 18 participants in the single-dose Phase 1 study to 208 in the Phase 3 open-label treatment extension study. All trials enrolled adults aged 18 years and older in the United States.