Multiple Dose Pharmacokinetics Depot Buprenorphine in Opioid-Dependent Subjects

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01738503

Enrollment

124

Registered

2012-11-30

Start date

2012-10-31

Completion date

2014-05-31

Last updated

2018-02-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Opioid Related Disorder

Keywords

Opioid Dependence, Buprenorphine, Depot, SUBUTEX, RBP-6000

Brief summary

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.

Detailed description

* 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.

Interventions

DRUGRBP-6000

18% Buprenorphine Sterile Solution for subcutaneous (SC) injection using the ATRIGEL® Delivery System. Each injection of RBP-6000 is separated by a minimum of 28 days and given on alternate sides of the participant's abdomen.

DRUGSubutex

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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	Days 85-113, 141-197	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.
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Day -1, Days 1-29, 85-113, 141-197	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
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Day -1, Days 1-29, 85-113, 141-197	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
Norbuprenorphine PK: Swing of Plasma Concentrations	Day -1, Days 1-29, 85-113, 141-197	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
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Day -1, Days 1-29, 85-113, 141-197	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
Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	Days 1-28, 85-113	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).
Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	Days 1-28, 85-113	Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.
Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)	Days 85-113, 141-197	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.
Participants With Treatment-Emergent Adverse Events (TEAEs)	Days -14 to -1 (Subutex treatment), Days 1-316 (RBP-6000 treatment)	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
Buprenorphine PK: % Fluctuation	Day -1, Days 1-29, 85-113, 141-197	% 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
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Day -1, Days 1-29, 85-113, 141-197	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
Buprenorphine PK: Average Plasma Concentration (Cavg)	Day -1, Days 1-29, 85-113, 141-197	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
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Day -1, Days 1-29, 85-113, 141-197	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
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Day -1, Days 1-29, 85-113, 141-197	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
Buprenorphine PK: Swing of Plasma Concentrations	Day -1, Days 1-29, 85-113, 141-197	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
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Day -1, Days 1-29, 85-113, 141-197	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
Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	Days 1-28, 85-113	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).
Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	Days 1-28, 85-113	Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.
Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Days 85-113, 141-169	Apparent clearance at steady-state (CLss/F) = Dose / AUCtau (tau was 28 days).
Buprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 (AUC0-∞)	Days 85-113	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.
Buprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	Days 85-113	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.
Norbuprenorphine PK: % Fluctuation	Day -1, Days 1-29, 85-113, 141-197	% 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
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Day -1, Days 1-29, 85-113, 141-197	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
Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Day -1, Days 1-29, 85-113, 141-197	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

Secondary

Measure	Time frame	Description
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141	The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the participant rates on a scale of 0 (not at all) to 4 (extremely) for a full scale of 0 (no withdrawal symptoms) to 64 (extreme withdrawal symptoms). Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of withdrawal symptoms.
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141	The Total Score was the sum of 10 questions regarding cravings each ranging from 0 (no craving) - 10 (extreme craving) for a total range from 0 (no cravings) to 100 (most intense craving I have ever had). Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of craving symptoms.
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Baseline (screening Day -15), Days 1, 7, 29, 57, 85, 141	The CGI-S is a 7-item scale completed by the clinician used to rate the severity of symptoms. The total range is 1 (normal, not at all ill) to 7 (most extremely ill). Baseline was defined as value from screening (Day -13). The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing (not applicable for Day 7) and reported as change from baseline values. Negative change from baseline values indicate a lessening of the severity of symptoms.
Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Baseline (Day 1), Days 7, 29, 57, 85, 141	The CGI-I is a 7-item scale completed by the clinician used to rate their impression of how much the participant has improved over a baseline state. The total range is 1 (very much improved) to 7 (very much worse). Baseline was defined as value from Day 1. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing (not applicable for Day 7) and reported as change from baseline values. Negative change from baseline values indicate an improvement.
Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Screening (summary of lifetime), Screening (last 6 months), Day 65, Day 113, End of Study (up to day 365)	The scale used in the C-SSRS is a continuous variable ranging from 0 (no suicidal ideation present) to 5 (active ideation with specific plan and intent). Only participants with suicidal ideation (scale of 1-5) are reported. 1=desire to be dead to 5=active ideation with specific plan and intent.
Percentage of Urine Drug Screen Samples Negative for Opioids	Day 1 to End of Study (up to day 365)	Urine samples were screened for the following drugs: * opiates * cocaine * amphetamines * methadone * cannabinoids * barbiturates * buprenorphine. Buprenorphine was only included in the urine drug screen at screening and Day -14 to determine if the subject had used any buprenorphine-containing products prior to the start of SUBUTEX SL tablet dosing. * benzodiazepines * methamphetamine * phencyclidine Urine drug screens were run every day when the participant was an inpatient; every 2-3 days when the participant was an outpatient. Drug screens were run less often for those participants in the PET substudy.
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141	COWS is an 11-item instrument used to assess symptoms of opioid withdrawal (Wesson et al., 1999). The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderate/severe withdrawal, and 37-48 severe withdrawal. Each participant was to be assessed by the same qualified and trained individuals throughout the course of the study as much as possible. Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of withdrawal symptoms.

Countries

United States

Participant flow

Pre-assignment details

A total of 395 subjects provided informed consent to participate in the main study and underwent screening procedures. Of these 395 subjects, 124 received study treatment.

Participants by arm

Arm	Count
Group 1 (8 mg) RBP-6000: 50 mg 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.	15
Group 2 (12 mg) RBP-6000: 100 mg 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	15
Group 3 (24 mg) RBP-6000: 200 mg 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 reach Day 113 (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.	15
Group 4 (8 mg) RBP-6000: 100 mg 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.	15
Group 5 (14 mg) RBP-6000: 200 mg 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 reach Day 113 (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.	15
Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 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 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	14
Total	89

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006
Induction/Stabilization (Days -14 to -1)	Other	35	0	0	0	0	0	0
PET Imaging Sub-study	Adverse Event	0	0	0	0	0	1	0
PET Imaging Sub-study	Scheduling issues with imaging facility	0	0	0	0	0	1	1
Treatment Period	Adverse Event	0	1	0	1	2	2	2
Treatment Period	Lost to Follow-up	0	0	3	4	1	1	5
Treatment Period	Other	0	0	1	0	0	0	0
Treatment Period	Protocol Violation	0	3	1	0	4	2	0
Treatment Period	Withdrawal by Subject	0	1	0	1	1	1	1

Baseline characteristics

Characteristic	Group 2 (12 mg) RBP-6000: 100 mg	Total	Group 6 (8-24 mg) RBP-6000: 300 mg	Group 5 (14 mg) RBP-6000: 200 mg	Group 4 (8 mg) RBP-6000: 100 mg	Group 1 (8 mg) RBP-6000: 50 mg	Group 3 (24 mg) RBP-6000: 200 mg
Age, Continuous	31.1 years STANDARD_DEVIATION 11.14	33.8 years STANDARD_DEVIATION 12.1	32.9 years STANDARD_DEVIATION 11	36.2 years STANDARD_DEVIATION 12.85	36.1 years STANDARD_DEVIATION 14.87	36.5 years STANDARD_DEVIATION 11.36	30.1 years STANDARD_DEVIATION 11.21
Body Mass Index	24.67 kg/m^2 STANDARD_DEVIATION 3.239	24.64 kg/m^2 STANDARD_DEVIATION 3.394	25.36 kg/m^2 STANDARD_DEVIATION 3.355	25.67 kg/m^2 STANDARD_DEVIATION 3.635	25.26 kg/m^2 STANDARD_DEVIATION 4.295	23.55 kg/m^2 STANDARD_DEVIATION 3.084	23.39 kg/m^2 STANDARD_DEVIATION 2.298
Height	172.87 cm STANDARD_DEVIATION 8.532	171.22 cm STANDARD_DEVIATION 9.906	170.64 cm STANDARD_DEVIATION 11.469	168.71 cm STANDARD_DEVIATION 10.963	171.17 cm STANDARD_DEVIATION 8.701	173.41 cm STANDARD_DEVIATION 8.514	170.50 cm STANDARD_DEVIATION 11.738
Heroin Use	9.78 years STANDARD_DEVIATION 11.454	9.62 years STANDARD_DEVIATION 10.292	8.56 years STANDARD_DEVIATION 12.471	10.70 years STANDARD_DEVIATION 7.987	11.64 years STANDARD_DEVIATION 12.549	11.25 years STANDARD_DEVIATION 10.463	5.00 years STANDARD_DEVIATION 5.604
Other Opioid Use	6.18 years STANDARD_DEVIATION 4.191	6.15 years STANDARD_DEVIATION 6.165	6.30 years STANDARD_DEVIATION 8.693	8.36 years STANDARD_DEVIATION 9.77	5.27 years STANDARD_DEVIATION 3.927	6.75 years STANDARD_DEVIATION 5.545	4.17 years STANDARD_DEVIATION 2.887
Race/Ethnicity, Customized Hispanic or Latino	1 Participants	4 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	14 Participants	85 Participants	13 Participants	14 Participants	14 Participants	15 Participants	15 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	3 Participants	26 Participants	3 Participants	5 Participants	5 Participants	7 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	11 Participants	62 Participants	11 Participants	10 Participants	10 Participants	8 Participants	12 Participants
Sex: Female, Male Female	5 Participants	29 Participants	4 Participants	6 Participants	6 Participants	3 Participants	5 Participants
Sex: Female, Male Male	10 Participants	60 Participants	10 Participants	9 Participants	9 Participants	12 Participants	10 Participants
Smoking History (Nicotine Use)	10.64 years STANDARD_DEVIATION 5.387	15.30 years STANDARD_DEVIATION 11.243	17.31 years STANDARD_DEVIATION 13.054	20.07 years STANDARD_DEVIATION 11.526	19.83 years STANDARD_DEVIATION 14.282	15.14 years STANDARD_DEVIATION 10.596	9.57 years STANDARD_DEVIATION 8.225
Weight	73.71 kg STANDARD_DEVIATION 10.411	72.50 kg STANDARD_DEVIATION 13.159	74.64 kg STANDARD_DEVIATION 16.825	73.16 kg STANDARD_DEVIATION 12.753	74.43 kg STANDARD_DEVIATION 15.995	71.12 kg STANDARD_DEVIATION 12.929	68.08 kg STANDARD_DEVIATION 9.9

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	0 / 35	0 / 15	0 / 15	0 / 15	0 / 15	0 / 15	0 / 14
other Total, other adverse events	24 / 35	15 / 15	15 / 15	15 / 15	15 / 15	15 / 15	14 / 14
serious Total, serious adverse events	0 / 35	0 / 15	2 / 15	1 / 15	1 / 15	2 / 15	0 / 14

Outcome results

Primary

Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))

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).

Time frame: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Arm	Measure	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	2.580 ratio	Standard Deviation 0.9662
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	2.738 ratio	Standard Deviation 0.5104
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	3.456 ratio	Standard Deviation 0.9296
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	3.379 ratio	Standard Deviation 0.9182
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	2.837 ratio	Standard Deviation 0.866
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	3.573 ratio	Standard Deviation 0.566

Primary

Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))

Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.

Time frame: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Arm	Measure	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	1.380 ratio	Standard Deviation 0.461
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	1.560 ratio	Standard Deviation 0.5322
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	1.766 ratio	Standard Deviation 0.5407
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	1.729 ratio	Standard Deviation 0.6106
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	1.559 ratio	Standard Deviation 0.2642
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	1.908 ratio	Standard Deviation 0.4411

Primary

Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6

Apparent clearance at steady-state (CLss/F) = Dose / AUCtau (tau was 28 days).

Time frame: Days 85-113, 141-169

Population: PK population

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 4	85.543 L/hour	Standard Deviation 34.6133
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 4	85.043 L/hour	Standard Deviation 21.9189
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 4	105.155 L/hour	Standard Deviation 23.4377
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 4	87.404 L/hour	Standard Deviation 21.0436
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 4	105.390 L/hour	Standard Deviation 29.3714
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 6	77.749 L/hour	Standard Deviation 8.3342
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 6	79.777 L/hour	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6	Injection 4	80.860 L/hour	Standard Deviation 15.8555

Primary

Buprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 (AUC0-∞)

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.

Time frame: Days 85-113

Population: PK population of participants whose data met requirements.

Arm	Measure	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 (AUC0-∞)	2280.295 hr*ng/mL	Standard Deviation 17.4444
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 (AUC0-∞)	3521.376 hr*ng/mL	—

Primary

Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)

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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Population: The PK analysis population was defined as any subject in Groups 1 - 6 who received a dose of RBP-6000 or at least 1 dose of SUBUTEX SL tablet and had an adequate number of PK samples collected to derive PK parameters.

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	667.611 hr*ng/mL	Standard Deviation 254.2712
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	35.250 hr*ng/mL	Standard Deviation 14.5405
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	208.013 hr*ng/mL	Standard Deviation 43.2691
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	246.650 hr*ng/mL	Standard Deviation 54.9881
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	69.845 hr*ng/mL	Standard Deviation 24.4947
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	46.855 hr*ng/mL	Standard Deviation 11.5533
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	28.452 hr*ng/mL	Standard Deviation 7.9415
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	596.568 hr*ng/mL	Standard Deviation 227.2414
SUBUTEX Only	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	24.922 hr*ng/mL	Standard Deviation 6.445
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	40.971 hr*ng/mL	Standard Deviation 12.6823
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	395.450 hr*ng/mL	Standard Deviation 115.3659
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	1272.047 hr*ng/mL	Standard Deviation 434.1013
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	56.231 hr*ng/mL	Standard Deviation 15.6411
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	72.453 hr*ng/mL	Standard Deviation 25.4451
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	1142.046 hr*ng/mL	Standard Deviation 380.1915
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	461.366 hr*ng/mL	Standard Deviation 142.2166
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	113.347 hr*ng/mL	Standard Deviation 29.776
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	36.981 hr*ng/mL	Standard Deviation 14.3565
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	541.226 hr*ng/mL	Standard Deviation 193.622
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	63.019 hr*ng/mL	Standard Deviation 16.4068
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	109.029 hr*ng/mL	Standard Deviation 30.2598
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	185.535 hr*ng/mL	Standard Deviation 48.233
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	1807.403 hr*ng/mL	Standard Deviation 441.0377
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	55.291 hr*ng/mL	Standard Deviation 17.0179
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	642.010 hr*ng/mL	Standard Deviation 228.0284
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	91.197 hr*ng/mL	Standard Deviation 27.4005
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	1932.068 hr*ng/mL	Standard Deviation 455.154
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	98.566 hr*ng/mL	Standard Deviation 17.8092
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	1275.098 hr*ng/mL	Standard Deviation 252.85
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	31.747 hr*ng/mL	Standard Deviation 13.218
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	368.925 hr*ng/mL	Standard Deviation 137.2231
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	413.438 hr*ng/mL	Standard Deviation 133.0365
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	47.633 hr*ng/mL	Standard Deviation 9.6147
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	30.029 hr*ng/mL	Standard Deviation 12.8676
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	62.395 hr*ng/mL	Standard Deviation 20.3054
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	1073.201 hr*ng/mL	Standard Deviation 240.7532
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 6 (0-48 hours)	216.540 hr*ng/mL	Standard Deviation 48.7904
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	1859.204 hr*ng/mL	Standard Deviation 477.7799
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 6 (2-28 days)	2209.11 hr*ng/mL	—
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	172.421 hr*ng/mL	Standard Deviation 29.3259
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	50.034 hr*ng/mL	Standard Deviation 11.4899
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	104.868 hr*ng/mL	Standard Deviation 22.6943
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	2051.989 hr*ng/mL	Standard Deviation 466.6935
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	756.053 hr*ng/mL	Standard Deviation 233.8099
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	81.417 hr*ng/mL	Standard Deviation 18.3829
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	46.681 hr*ng/mL	Standard Deviation 11.8403
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 6 (0-28 days)	2585.976 hr*ng/mL	Standard Deviation 276.6695
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	648.344 hr*ng/mL	Standard Deviation 217.2051
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	46.628 hr*ng/mL	Standard Deviation 23.2554
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	3230.873 hr*ng/mL	Standard Deviation 430.6718
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	3426.313 hr*ng/mL	Standard Deviation 672.5864
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	926.110 hr*ng/mL	Standard Deviation 285.6452
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	178.109 hr*ng/mL	Standard Deviation 43.2176
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	164.511 hr*ng/mL	Standard Deviation 47.8237
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	381.729 hr*ng/mL	Standard Deviation 81.4365
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 6 (0-24 hours)	155.779 hr*ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	85.090 hr*ng/mL	Standard Deviation 28.7163
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 6 (0-48 hours)	320.159 hr*ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	1268.012 hr*ng/mL	Standard Deviation 389.6719
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 6 (2-28 days)	3460.459 hr*ng/mL	—

Primary

Buprenorphine PK: Average Plasma Concentration (Cavg)

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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	0.993 ng/mL	Standard Deviation 0.3784
SUBUTEX Only	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.333 ng/mL	Standard Deviation 0.0693
SUBUTEX Only	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.367 ng/mL	Standard Deviation 0.0818
SUBUTEX Only	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	0.954 ng/mL	Standard Deviation 0.3642
SUBUTEX Only	Buprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	1.186 ng/mL	Standard Deviation 0.3309
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	1.893 ng/mL	Standard Deviation 0.646
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.687 ng/mL	Standard Deviation 0.2116
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.634 ng/mL	Standard Deviation 0.1849
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	1.830 ng/mL	Standard Deviation 0.6093
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	1.707 ng/mL	Standard Deviation 0.5284
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.955 ng/mL	Standard Deviation 0.3393
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	2.896 ng/mL	Standard Deviation 0.7068
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	2.875 ng/mL	Standard Deviation 0.6773
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.867 ng/mL	Standard Deviation 0.3103
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	2.626 ng/mL	Standard Deviation 0.6836
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.591 ng/mL	Standard Deviation 0.2199
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	1.897 ng/mL	Standard Deviation 0.3763
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.615 ng/mL	Standard Deviation 0.198
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	1.720 ng/mL	Standard Deviation 0.3858
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	1.251 ng/mL	Standard Deviation 0.5362
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 6	3.848 ng/mL	Standard Deviation 0.4117
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	1.945 ng/mL	Standard Deviation 0.4933
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	1.039 ng/mL	Standard Deviation 0.3481
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	2.979 ng/mL	Standard Deviation 0.7657
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 6	3.540 ng/mL	—
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	1.125 ng/mL	Standard Deviation 0.3331
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	3.054 ng/mL	Standard Deviation 0.6945
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 6	5.546 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	5.491 ng/mL	Standard Deviation 1.0779
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	1.484 ng/mL	Standard Deviation 0.4578
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	1.943 ng/mL	Standard Deviation 0.969
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	4.808 ng/mL	Standard Deviation 0.6409
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	1.887 ng/mL	Standard Deviation 0.5799

Primary

Buprenorphine PK: % Fluctuation

% 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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: % Fluctuation	Overall: Injection 4	152.755 % of average concentration	Standard Deviation 75.3194
SUBUTEX Only	Buprenorphine PK: % Fluctuation	Plateau: Injection 1	213.664 % of average concentration	Standard Deviation 50.7221
SUBUTEX Only	Buprenorphine PK: % Fluctuation	Overall: Injection 1	315.777 % of average concentration	Standard Deviation 106.6237
SUBUTEX Only	Buprenorphine PK: % Fluctuation	Plateau: Injection 4	68.333 % of average concentration	Standard Deviation 16.8729
SUBUTEX Only	Buprenorphine PK: % Fluctuation	Sublingual Period	256.993 % of average concentration	Standard Deviation 68.4944
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 4	95.140 % of average concentration	Standard Deviation 20.9504
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 1	234.098 % of average concentration	Standard Deviation 60.7481
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 1	175.068 % of average concentration	Standard Deviation 69.0037
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 4	63.611 % of average concentration	Standard Deviation 27.6839
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: % Fluctuation	Sublingual Period	272.702 % of average concentration	Standard Deviation 62.1424
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 1	234.598 % of average concentration	Standard Deviation 66.4979
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 4	42.699 % of average concentration	Standard Deviation 5.6645
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 4	75.633 % of average concentration	Standard Deviation 17.3765
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 1	168.963 % of average concentration	Standard Deviation 31.8302
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Sublingual Period	233.978 % of average concentration	Standard Deviation 84.1776
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 1	140.924 % of average concentration	Standard Deviation 39.3779
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 4	77.067 % of average concentration	Standard Deviation 21.4559
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 1	213.254 % of average concentration	Standard Deviation 68.1754
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 4	41.275 % of average concentration	Standard Deviation 14.1786
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Sublingual Period	268.690 % of average concentration	Standard Deviation 54.5116
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 6	54.789 % of average concentration	Standard Deviation 1.6355
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Sublingual Period	227.874 % of average concentration	Standard Deviation 69.1437
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 1	135.433 % of average concentration	Standard Deviation 31.4609
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 4	47.282 % of average concentration	Standard Deviation 21.0395
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 6	22.597 % of average concentration	—
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 1	206.691 % of average concentration	Standard Deviation 79.9858
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 4	75.202 % of average concentration	Standard Deviation 28.4598
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 6	31.376 % of average concentration	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 4	53.383 % of average concentration	Standard Deviation 20.9467
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Plateau: Injection 1	107.909 % of average concentration	Standard Deviation 33.9246
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Sublingual Period	245.513 % of average concentration	Standard Deviation 61.2524
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 4	83.695 % of average concentration	Standard Deviation 12.8165
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: % Fluctuation	Overall: Injection 1	220.854 % of average concentration	Standard Deviation 70.3346

Primary

Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)

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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	2.085 ng/mL	Standard Deviation 1.4381
SUBUTEX Only	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	0.853 ng/mL	Standard Deviation 0.2687
SUBUTEX Only	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	2.085 ng/mL	Standard Deviation 1.4381
SUBUTEX Only	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	3.521 ng/mL	Standard Deviation 1.0407
SUBUTEX Only	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	1.352 ng/mL	Standard Deviation 0.4641
SUBUTEX Only	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	1.384 ng/mL	Standard Deviation 0.4767
SUBUTEX Only	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	1.352 ng/mL	Standard Deviation 0.4641
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	2.023 ng/mL	Standard Deviation 0.8251
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	5.350 ng/mL	Standard Deviation 1.734
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	1.916 ng/mL	Standard Deviation 0.6773
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	2.958 ng/mL	Standard Deviation 0.9624
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	1.518 ng/mL	Standard Deviation 0.8167
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	2.590 ng/mL	Standard Deviation 0.8536
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	3.066 ng/mL	Standard Deviation 0.8658
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	2.732 ng/mL	Standard Deviation 0.7866
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	2.018 ng/mL	Standard Deviation 0.6205
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	2.755 ng/mL	Standard Deviation 0.763
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	4.526 ng/mL	Standard Deviation 1.3078
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	4.526 ng/mL	Standard Deviation 1.3078
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	7.571 ng/mL	Standard Deviation 3.0928
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	3.776 ng/mL	Standard Deviation 0.897
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	2.549 ng/mL	Standard Deviation 0.4797
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	2.211 ng/mL	Standard Deviation 0.3824
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	1.686 ng/mL	Standard Deviation 0.62
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	1.686 ng/mL	Standard Deviation 0.62
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	2.554 ng/mL	Standard Deviation 0.4775
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	3.964 ng/mL	Standard Deviation 1.9131
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	1.174 ng/mL	Standard Deviation 0.3432
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	4.404 ng/mL	Standard Deviation 0.9231
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	4.404 ng/mL	Standard Deviation 0.9231
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 6 (0-48 hours)	5.015 ng/mL	Standard Deviation 0.898
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	2.112 ng/mL	Standard Deviation 0.6935
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 6	5.015 ng/mL	Standard Deviation 0.898
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	3.780 ng/mL	Standard Deviation 0.6646
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 6 (2-28 days)	4.650 ng/mL	Standard Deviation 0.891
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	5.260 ng/mL	Standard Deviation 1.5595
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	2.861 ng/mL	Standard Deviation 0.7136
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	2.861 ng/mL	Standard Deviation 0.7136
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 6 (0-48 hours)	7.140 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	4.817 ng/mL	Standard Deviation 1.4337
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	5.813 ng/mL	Standard Deviation 3.4264
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 6	7.140 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	2.975 ng/mL	Standard Deviation 0.8839
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	9.637 ng/mL	Standard Deviation 2.3409
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	9.637 ng/mL	Standard Deviation 2.3409
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	4.817 ng/mL	Standard Deviation 1.4337
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 6 (2-28 days)	6.550 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	7.452 ng/mL	Standard Deviation 1.6913

Primary

Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)

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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	0.524 ng/mL	Standard Deviation 0.2212
SUBUTEX Only	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	0.557 ng/mL	Standard Deviation 0.1559
SUBUTEX Only	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.206 ng/mL	Standard Deviation 0.0556
SUBUTEX Only	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	0.791 ng/mL	Standard Deviation 0.3017
SUBUTEX Only	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.206 ng/mL	Standard Deviation 0.0556
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	1.434 ng/mL	Standard Deviation 0.3706
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.388 ng/mL	Standard Deviation 0.1145
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	1.263 ng/mL	Standard Deviation 0.3574
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.375 ng/mL	Standard Deviation 0.1001
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	0.806 ng/mL	Standard Deviation 0.3638
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.600 ng/mL	Standard Deviation 0.2623
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.589 ng/mL	Standard Deviation 0.2522
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	1.385 ng/mL	Standard Deviation 0.4806
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	2.575 ng/mL	Standard Deviation 0.6439
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	2.121 ng/mL	Standard Deviation 0.4689
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	1.552 ng/mL	Standard Deviation 0.3448
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.410 ng/mL	Standard Deviation 0.1955
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.388 ng/mL	Standard Deviation 0.1554
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	0.568 ng/mL	Standard Deviation 0.2367
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	1.180 ng/mL	Standard Deviation 0.2803
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 6 (2-28 days)	3.325 ng/mL	Standard Deviation 0.1485
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	2.256 ng/mL	Standard Deviation 0.6472
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.700 ng/mL	Standard Deviation 0.2196
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	2.498 ng/mL	Standard Deviation 0.7269
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.714 ng/mL	Standard Deviation 0.2315
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	0.920 ng/mL	Standard Deviation 0.28
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 6	2.910 ng/mL	Standard Deviation 0.7354
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 6	4.290 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	0.927 ng/mL	Standard Deviation 0.4667
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	1.244 ng/mL	Standard Deviation 0.4455
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	4.600 ng/mL	Standard Deviation 0.7743
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 6 (2-28 days)	4.810 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.836 ng/mL	Standard Deviation 0.3756
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	4.043 ng/mL	Standard Deviation 0.6936

Primary

Buprenorphine PK: Swing of Plasma Concentrations

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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	656.884 percentage of Cmin	Standard Deviation 303.7135
SUBUTEX Only	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	279.713 percentage of Cmin	Standard Deviation 214.1821
SUBUTEX Only	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	586.788 percentage of Cmin	Standard Deviation 219.99
SUBUTEX Only	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	79.731 percentage of Cmin	Standard Deviation 27.3175
SUBUTEX Only	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	332.132 percentage of Cmin	Standard Deviation 127.9638
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	84.772 percentage of Cmin	Standard Deviation 48.3724
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	295.987 percentage of Cmin	Standard Deviation 229.0036
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	147.264 percentage of Cmin	Standard Deviation 48.3533
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	440.102 percentage of Cmin	Standard Deviation 200.5223
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	665.742 percentage of Cmin	Standard Deviation 314.653
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	253.417 percentage of Cmin	Standard Deviation 61.2944
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	399.355 percentage of Cmin	Standard Deviation 140.2055
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	493.475 percentage of Cmin	Standard Deviation 273.1229
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	47.479 percentage of Cmin	Standard Deviation 10.5422
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	112.812 percentage of Cmin	Standard Deviation 32.8955
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	44.874 percentage of Cmin	Standard Deviation 18.5656
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	350.591 percentage of Cmin	Standard Deviation 158.0245
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	223.388 percentage of Cmin	Standard Deviation 94.3116
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	597.543 percentage of Cmin	Standard Deviation 136.8431
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	120.236 percentage of Cmin	Standard Deviation 28.1402
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 6	39.390 percentage of Cmin	Standard Deviation 20.5703
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	103.271 percentage of Cmin	Standard Deviation 43.4914
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	336.666 percentage of Cmin	Standard Deviation 149.7124
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	57.889 percentage of Cmin	Standard Deviation 30.3975
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	197.895 percentage of Cmin	Standard Deviation 49.3822
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	500.322 percentage of Cmin	Standard Deviation 183.7474
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 6	73.993 percentage of Cmin	Standard Deviation 13.1102
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 6	66.434 percentage of Cmin	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	534.280 percentage of Cmin	Standard Deviation 217.8816
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	147.463 percentage of Cmin	Standard Deviation 66.0341
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	61.481 percentage of Cmin	Standard Deviation 24.0339
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 6	36.175 percentage of Cmin	—
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	548.179 percentage of Cmin	Standard Deviation 272.0431
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	138.783 percentage of Cmin	Standard Deviation 47.6186

Primary

Buprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4

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.

Time frame: Days 85-113

Population: PK population of participants whose data met requirements.

Arm	Measure	Value (MEAN)	Dispersion
SUBUTEX Only	Buprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	550.329 hours	Standard Deviation 36.7325
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	138.238 hours	—

Primary

Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)

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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEDIAN)
SUBUTEX Only	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
SUBUTEX Only	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
SUBUTEX Only	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	20.000 hours
SUBUTEX Only	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	20.000 hours
SUBUTEX Only	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	20.000 hours
SUBUTEX Only	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.000 hours
SUBUTEX Only	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	20.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	20.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	1.017 hours
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	20.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	20.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	20.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	1.117 hours
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	20.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	20.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	20.083 hours
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	20.083 hours
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	20.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	24.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	20.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	24.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	24.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	24.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 6 (0-48 hours)	24.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 6 (0-28 days)	24.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 6 (2-28 days)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	20.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	20.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	24.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	20.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 6 (0-28 days)	24.350 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 6 (0-48 hours)	24.350 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	24.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	20.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 6 (2-28 days)	48.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.000 hours

Primary

Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))

Time frame: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Arm	Measure	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	1.071 ratio	Standard Deviation 0.4044
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	1.924 ratio	Standard Deviation 1.9274
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	1.147 ratio	Standard Deviation 0.5899
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	1.709 ratio	Standard Deviation 0.4088
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	1.711 ratio	Standard Deviation 0.5931
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	1.247 ratio	Standard Deviation 0.6737

Primary

Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))

Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.

Time frame: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Arm	Measure	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	0.300 ratio	Standard Deviation 0.1294
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	0.697 ratio	Standard Deviation 0.9077
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	0.272 ratio	Standard Deviation 0.1131
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	0.548 ratio	Standard Deviation 0.2978
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	0.445 ratio	Standard Deviation 0.2231
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	0.730 ratio	Standard Deviation 0.583

Primary

Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)

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.

Time frame: Days 85-113, 141-197

Population: PK population of participants whose data met requirements.

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)	Overall: Injection 4 (0-28 days)	499.733 hr*ng/mL	Standard Deviation 391.9606
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)	Overall: Injection 4 (0-28 days)	1583.219 hr*ng/mL	Standard Deviation 1471.7341
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)	Overall: Injection 4 (0-28 days)	639.892 hr*ng/mL	Standard Deviation 135.9113
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)	Overall: Injection 4 (0-28 days)	1472.769 hr*ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)	Overall: Injection 6 (0-28 days)	737.097 hr*ng/mL	—

Primary

Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	122.265 hr*ng/mL	Standard Deviation 43.4215
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	182.405 hr*ng/mL	Standard Deviation 91.5308
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	6.274 hr*ng/mL	Standard Deviation 2.7973
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	15.435 hr*ng/mL	Standard Deviation 8.0734
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	32.465 hr*ng/mL	Standard Deviation 14.2953
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	181.912 hr*ng/mL	Standard Deviation 81.61
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	60.834 hr*ng/mL	Standard Deviation 27.8301
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	166.360 hr*ng/mL	Standard Deviation 82.1264
SUBUTEX Only	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	42.536 hr*ng/mL	Standard Deviation 17.9975
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	29.401 hr*ng/mL	Standard Deviation 16.3007
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	52.878 hr*ng/mL	Standard Deviation 28.0773
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	557.707 hr*ng/mL	Standard Deviation 471.2095
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	98.705 hr*ng/mL	Standard Deviation 54.0709
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	523.076 hr*ng/mL	Standard Deviation 431.7284
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	72.339 hr*ng/mL	Standard Deviation 35.1371
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	15.199 hr*ng/mL	Standard Deviation 11.7793
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	343.357 hr*ng/mL	Standard Deviation 150.5029
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	209.679 hr*ng/mL	Standard Deviation 85.5994
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	541.539 hr*ng/mL	Standard Deviation 176.5176
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	99.040 hr*ng/mL	Standard Deviation 30.8899
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	134.739 hr*ng/mL	Standard Deviation 40.4214
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	519.103 hr*ng/mL	Standard Deviation 236.8835
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	384.101 hr*ng/mL	Standard Deviation 133.4394
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	50.185 hr*ng/mL	Standard Deviation 19.6558
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	180.685 hr*ng/mL	Standard Deviation 53.1546
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	570.958 hr*ng/mL	Standard Deviation 254.4439
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	22.870 hr*ng/mL	Standard Deviation 9.3521
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	197.483 hr*ng/mL	Standard Deviation 59.5501
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	49.312 hr*ng/mL	Standard Deviation 22.605
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	69.878 hr*ng/mL	Standard Deviation 26.1289
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	30.755 hr*ng/mL	Standard Deviation 11.0344
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	410.621 hr*ng/mL	Standard Deviation 146.1564
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	37.446 hr*ng/mL	Standard Deviation 15.9959
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	261.745 hr*ng/mL	Standard Deviation 81.3672
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	13.807 hr*ng/mL	Standard Deviation 5.3021
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	452.892 hr*ng/mL	Standard Deviation 152.6941
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 6 (0-48 hours)	59.352 hr*ng/mL	Standard Deviation 2.2741
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	673.245 hr*ng/mL	Standard Deviation 167.146
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	16.301 hr*ng/mL	Standard Deviation 6.4778
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	426.283 hr*ng/mL	Standard Deviation 224.4167
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	131.277 hr*ng/mL	Standard Deviation 82.0351
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	295.342 hr*ng/mL	Standard Deviation 142.3582
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	65.558 hr*ng/mL	Standard Deviation 25.0632
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 6 (0-28 days)	814.570 hr*ng/mL	Standard Deviation 306.2799
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 6 (2-28 days)	537.212 hr*ng/mL	—
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	68.660 hr*ng/mL	Standard Deviation 38.8033
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	45.941 hr*ng/mL	Standard Deviation 24.8979
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	550.225 hr*ng/mL	Standard Deviation 215.6699
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 1 (0-48 hours)	148.016 hr*ng/mL	Standard Deviation 97.0872
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-24 hours)	80.525 hr*ng/mL	Standard Deviation 51.3662
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 6 (0-48 hours)	90.719 hr*ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-28 days)	658.609 hr*ng/mL	Standard Deviation 159.7954
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 1 (0-28 days)	688.487 hr*ng/mL	Standard Deviation 429.8748
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Initial Burst: Injection 4 (0-48 hours)	101.888 hr*ng/mL	Standard Deviation 39.8768
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 1 (2-28 days)	513.577 hr*ng/mL	Standard Deviation 322.852
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 6 (0-24 hours)	37.093 hr*ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Overall: Injection 4 (0-24 hours)	43.722 hr*ng/mL	Standard Deviation 16.4542
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Sublingual Period (0-24 hours)	98.407 hr*ng/mL	Standard Deviation 81.7085
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 6 (2-28 days)	592.199 hr*ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)	Plateau: Injection 4 (2-28 days)	1208.505 hr*ng/mL	Standard Deviation 463.9637

Primary

Norbuprenorphine PK: Average Plasma Concentration (Cavg)

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	0.271 ng/mL	Standard Deviation 0.1362
SUBUTEX Only	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.196 ng/mL	Standard Deviation 0.0696
SUBUTEX Only	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.271 ng/mL	Standard Deviation 0.1214
SUBUTEX Only	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	0.267 ng/mL	Standard Deviation 0.1316
SUBUTEX Only	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	1.772 ng/mL	Standard Deviation 0.7499
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	0.830 ng/mL	Standard Deviation 0.7012
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.511 ng/mL	Standard Deviation 0.224
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.336 ng/mL	Standard Deviation 0.1372
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	0.838 ng/mL	Standard Deviation 0.6919
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	3.014 ng/mL	Standard Deviation 1.464
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.806 ng/mL	Standard Deviation 0.2627
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	0.832 ng/mL	Standard Deviation 0.3796
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	0.850 ng/mL	Standard Deviation 0.3786
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.616 ng/mL	Standard Deviation 0.2138
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	5.614 ng/mL	Standard Deviation 1.6842
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.316 ng/mL	Standard Deviation 0.0954
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	0.674 ng/mL	Standard Deviation 0.2272
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.390 ng/mL	Standard Deviation 0.1211
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	0.658 ng/mL	Standard Deviation 0.2342
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	2.055 ng/mL	Standard Deviation 0.9419
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 6	1.212 ng/mL	Standard Deviation 0.4558
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	2.732 ng/mL	Standard Deviation 1.0443
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.473 ng/mL	Standard Deviation 0.2281
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	0.882 ng/mL	Standard Deviation 0.3456
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 6	0.861 ng/mL	—
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	0.634 ng/mL	Standard Deviation 0.334
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	1.002 ng/mL	Standard Deviation 0.2487
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 6	0.949 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 4	1.937 ng/mL	Standard Deviation 0.7435
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Plateau: Injection 1	0.823 ng/mL	Standard Deviation 0.5174
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Sublingual Period	4.100 ng/mL	Standard Deviation 3.4045
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 4	0.980 ng/mL	Standard Deviation 0.2378
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Average Plasma Concentration (Cavg)	Overall: Injection 1	1.025 ng/mL	Standard Deviation 0.6397

Primary

Norbuprenorphine PK: % Fluctuation

% 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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: % Fluctuation	Overall: Injection 4	128.273 % of average concentration	Standard Deviation 31.6391
SUBUTEX Only	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 1	577.952 % of average concentration	Standard Deviation 119.5038
SUBUTEX Only	Norbuprenorphine PK: % Fluctuation	Overall: Injection 1	612.998 % of average concentration	Standard Deviation 141.7474
SUBUTEX Only	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 4	114.801 % of average concentration	Standard Deviation 33.7254
SUBUTEX Only	Norbuprenorphine PK: % Fluctuation	Sublingual Period	69.798 % of average concentration	Standard Deviation 21.5137
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 4	131.080 % of average concentration	Standard Deviation 57.4294
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 1	502.856 % of average concentration	Standard Deviation 101.2508
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 1	475.800 % of average concentration	Standard Deviation 149.9103
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 4	127.106 % of average concentration	Standard Deviation 64.0505
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: % Fluctuation	Sublingual Period	94.132 % of average concentration	Standard Deviation 43.7842
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 1	685.962 % of average concentration	Standard Deviation 195.9687
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 4	110.567 % of average concentration	Standard Deviation 42.0264
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 4	127.005 % of average concentration	Standard Deviation 37.8487
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 1	504.540 % of average concentration	Standard Deviation 170.1714
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Sublingual Period	79.225 % of average concentration	Standard Deviation 19.2173
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 1	403.009 % of average concentration	Standard Deviation 115.9346
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 4	95.960 % of average concentration	Standard Deviation 18.6296
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 1	497.361 % of average concentration	Standard Deviation 138.6539
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 4	77.455 % of average concentration	Standard Deviation 24.7664
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Sublingual Period	82.834 % of average concentration	Standard Deviation 29.0182
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 6	94.048 % of average concentration	Standard Deviation 7.4553
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Sublingual Period	89.832 % of average concentration	Standard Deviation 31.3881
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 1	407.217 % of average concentration	Standard Deviation 160.6071
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 4	101.898 % of average concentration	Standard Deviation 28.8808
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 6	91.763 % of average concentration	—
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 1	609.481 % of average concentration	Standard Deviation 145.865
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 4	131.650 % of average concentration	Standard Deviation 43.626
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 6	242.246 % of average concentration	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 4	83.579 % of average concentration	Standard Deviation 18.6265
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Plateau: Injection 1	354.764 % of average concentration	Standard Deviation 136.5715
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Sublingual Period	71.213 % of average concentration	Standard Deviation 18.7721
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 4	102.192 % of average concentration	Standard Deviation 12.2405
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: % Fluctuation	Overall: Injection 1	468.074 % of average concentration	Standard Deviation 186.0526

Primary

Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	0.474 ng/mL	Standard Deviation 0.2849
SUBUTEX Only	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	1.165 ng/mL	Standard Deviation 0.5506
SUBUTEX Only	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	0.462 ng/mL	Standard Deviation 0.2894
SUBUTEX Only	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	2.559 ng/mL	Standard Deviation 1.059
SUBUTEX Only	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	1.698 ng/mL	Standard Deviation 0.7748
SUBUTEX Only	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	0.464 ng/mL	Standard Deviation 0.2903
SUBUTEX Only	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	1.674 ng/mL	Standard Deviation 0.7498
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	2.753 ng/mL	Standard Deviation 1.4051
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	4.941 ng/mL	Standard Deviation 2.5414
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	2.704 ng/mL	Standard Deviation 1.3861
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	0.966 ng/mL	Standard Deviation 0.5829
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	1.904 ng/mL	Standard Deviation 1.0984
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	1.423 ng/mL	Standard Deviation 1.1714
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	1.431 ng/mL	Standard Deviation 1.1652
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	5,572 ng/mL	Standard Deviation 1.9291
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	3.201 ng/mL	Standard Deviation 1.1802
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	5.335 ng/mL	Standard Deviation 1.7751
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	1.343 ng/mL	Standard Deviation 0.4299
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	1.456 ng/mL	Standard Deviation 0.4572
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	8.515 ng/mL	Standard Deviation 2.3854
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	1.387 ng/mL	Standard Deviation 0.4635
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	0.799 ng/mL	Standard Deviation 0.2673
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	0.926 ng/mL	Standard Deviation 0.3107
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	1.965 ng/mL	Standard Deviation 0.7884
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	1.977 ng/mL	Standard Deviation 0.788
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	0.929 ng/mL	Standard Deviation 0.3058
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	3.268 ng/mL	Standard Deviation 1.6946
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	1.320 ng/mL	Standard Deviation 0.4278
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	1.539 ng/mL	Standard Deviation 0.6406
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	1.305 ng/mL	Standard Deviation 0.5998
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 6 (0-48 hours)	1.885 ng/mL	Standard Deviation 0.6152
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	2.203 ng/mL	Standard Deviation 1.4464
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 6	1.885 ng/mL	Standard Deviation 0.6152
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	1.420 ng/mL	Standard Deviation 0.7152
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 6 (2-28 days)	1.885 ng/mL	Standard Deviation 0.6152
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	5.268 ng/mL	Standard Deviation 1.9934
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	3.989 ng/mL	Standard Deviation 2.3167
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	3.878 ng/mL	Standard Deviation 2.1658
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 6 (0-48 hours)	2.620 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 1	4.555 ng/mL	Standard Deviation 3.101
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Sublingual Period (0-24 hours)	5.820 ng/mL	Standard Deviation 4.7007
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 6	2.620 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 1 (2-28 days)	3.212 ng/mL	Standard Deviation 2.881
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Overall: Injection 4	2.769 ng/mL	Standard Deviation 1.2538
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 4 (0-48 hours)	2.769 ng/mL	Standard Deviation 1.2538
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Initial Burst: Injection 1 (0-48 hours)	4.496 ng/mL	Standard Deviation 3.0242
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 6 (2-28 days)	2.620 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)	Plateau: Injection 4 (2-28 days)	2.710 ng/mL	Standard Deviation 1.1727

Primary

Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	1.361 ng/mL	Standard Deviation 0.601
SUBUTEX Only	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	0.125 ng/mL	Standard Deviation 0.0539
SUBUTEX Only	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.057 ng/mL	Standard Deviation 0.0202
SUBUTEX Only	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	0.165 ng/mL	Standard Deviation 0.0708
SUBUTEX Only	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.057 ng/mL	Standard Deviation 0.0202
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	0.432 ng/mL	Standard Deviation 0.4181
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.099 ng/mL	Standard Deviation 0.0447
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	0.327 ng/mL	Standard Deviation 0.2592
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.098 ng/mL	Standard Deviation 0.0441
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	2.342 ng/mL	Standard Deviation 1.2494
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.162 ng/mL	Standard Deviation 0.0827
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.162 ng/mL	Standard Deviation 0.0827
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	4.287 ng/mL	Standard Deviation 1.3351
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	0.548 ng/mL	Standard Deviation 0.2119
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	0.461 ng/mL	Standard Deviation 0.2292
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	0.439 ng/mL	Standard Deviation 0.155
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.152 ng/mL	Standard Deviation 0.1427
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.119 ng/mL	Standard Deviation 0.0592
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	1.582 ng/mL	Standard Deviation 0.7554
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	0.349 ng/mL	Standard Deviation 0.1609
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 6 (2-28 days)	0.895 ng/mL	Standard Deviation 0.3323
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	0.459 ng/mL	Standard Deviation 0.2191
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.177 ng/mL	Standard Deviation 0.0919
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	0.587 ng/mL	Standard Deviation 0.3165
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.177 ng/mL	Standard Deviation 0.0919
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	2.482 ng/mL	Standard Deviation 1.1788
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 6	0.728 ng/mL	Standard Deviation 0.0962
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 6	0.281 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Sublingual Period (0-24 hours)	2.923 ng/mL	Standard Deviation 2.1949
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 1 (2-28 days)	0.258 ng/mL	Standard Deviation 0.1289
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 4 (2-28 days)	1.234 ng/mL	Standard Deviation 0.5279
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Plateau: Injection 6 (2-28 days)	0.321 ng/mL	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 1	0.301 ng/mL	Standard Deviation 0.218
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)	Overall: Injection 4	0.982 ng/mL	Standard Deviation 0.3281

Primary

Norbuprenorphine PK: Swing of Plasma Concentrations

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

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	180.340 percentage of Cmin	Standard Deviation 82.996
SUBUTEX Only	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	2903.100 percentage of Cmin	Standard Deviation 1102.0127
SUBUTEX Only	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	322.876 percentage of Cmin	Standard Deviation 297.9631
SUBUTEX Only	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	1993.328 percentage of Cmin	Standard Deviation 1002.6237
SUBUTEX Only	Norbuprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	93.472 percentage of Cmin	Standard Deviation 33.4835
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	379.301 percentage of Cmin	Standard Deviation 371.3835
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	2812.484 percentage of Cmin	Standard Deviation 1305.9088
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	130.823 percentage of Cmin	Standard Deviation 74.2916
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	289.316 percentage of Cmin	Standard Deviation 271.1318
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	1871.238 percentage of Cmin	Standard Deviation 933.9815
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	102.059 percentage of Cmin	Standard Deviation 29.6116
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	4477.582 percentage of Cmin	Standard Deviation 3470.4282
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	2531.386 percentage of Cmin	Standard Deviation 1775.806
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	171.673 percentage of Cmin	Standard Deviation 98.3404
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	265.586 percentage of Cmin	Standard Deviation 132.0434
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	186.942 percentage of Cmin	Standard Deviation 65.4013
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	109.416 percentage of Cmin	Standard Deviation 42.1913
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	1188.490 percentage of Cmin	Standard Deviation 491.1526
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	121.682 percentage of Cmin	Standard Deviation 62.5967
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	1776.276 percentage of Cmin	Standard Deviation 923.9753
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 6	112.503 percentage of Cmin	Standard Deviation 10.1733
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	151.990 percentage of Cmin	Standard Deviation 82.836
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	1210.967 percentage of Cmin	Standard Deviation 874.2858
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	2355.099 percentage of Cmin	Standard Deviation 1345.4616
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	124.601 percentage of Cmin	Standard Deviation 45.9786
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	272.260 percentage of Cmin	Standard Deviation 139.1806
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 6	155.577 percentage of Cmin	Standard Deviation 50.7422
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 4	118.215 percentage of Cmin	Standard Deviation 42.3788
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 6	716.199 percentage of Cmin	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 4	173.090 percentage of Cmin	Standard Deviation 51.8058
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 1	2116.996 percentage of Cmin	Standard Deviation 2015.7199
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Plateau: Injection 1	1250.370 percentage of Cmin	Standard Deviation 866.186
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Sublingual Period	101.558 percentage of Cmin	Standard Deviation 38.5511
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Swing of Plasma Concentrations	Overall: Injection 6	832.384 percentage of Cmin	—

Primary

Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4

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.

Time frame: Days 85-113, 141-197

Population: PK population of participants whose data met requirements.

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	Overall: Injection 4 (0-28 days)	405.325 hours	Standard Deviation 47.4883
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	Overall: Injection 4 (0-28 days)	241.914 hours	Standard Deviation 114.8553
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	Overall: Injection 4 (0-28 days)	334.080 hours	Standard Deviation 48.0676
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	Overall: Injection 4 (0-28 days)	310.879 hours	—
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	Overall: Injection 6 (0-28 days)	158.840 hours	—

Primary

Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)

Time frame: Day -1, Days 1-29, 85-113, 141-197

Arm	Measure	Group	Value (MEDIAN)
SUBUTEX Only	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	48.000 hours
SUBUTEX Only	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
SUBUTEX Only	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	48.000 hours
SUBUTEX Only	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
SUBUTEX Only	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	8.000 hours
SUBUTEX Only	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.000 hours
SUBUTEX Only	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	8.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	6.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	1.017 hours
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	6.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	48.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	96.883 hours
Group 1 (8 mg) RBP-6000: 50 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	48.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	2.525 hours
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	4.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	48.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	48.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	1.000 hours
Group 2 (12 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	48.100 hours
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	39.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	182.808 hours
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	12.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	6.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	182.808 hours
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
Group 3 (24 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	30.067 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	24.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 6 (0-48 hours)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 6 (0-28 days)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	167.017 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 6 (2-28 days)	48.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	4.000 hours
Group 4 (8 mg) RBP-6000: 100 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	6.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 6 (0-48 hours)	48.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 1 (0-28 days)	4.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Sublingual Period (0-24 hours)	2.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 6 (0-28 days)	48.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 1 (2-28 days)	48.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Overall: Injection 4 (0-28 days)	12.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 4 (0-48 hours)	12.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Initial Burst: Injection 1 (0-48 hours)	4.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 6 (2-28 days)	48.000 hours
Group 5 (14 mg) RBP-6000: 200 mg	Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)	Plateau: Injection 4 (2-28 days)	303.133 hours

Primary

Participants With Treatment-Emergent Adverse Events (TEAEs)

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

Time frame: Days -14 to -1 (Subutex treatment), Days 1-316 (RBP-6000 treatment)

Population: Safety analysis group

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SUBUTEX Only	Participants With Treatment-Emergent Adverse Events (TEAEs)	Withdrew from study due to a TEAE	0 Participants
SUBUTEX Only	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE related to study drug	0 Participants
SUBUTEX Only	Participants With Treatment-Emergent Adverse Events (TEAEs)	Deaths	0 Participants
SUBUTEX Only	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE	24 Participants
SUBUTEX Only	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 Severe TEAE	1 Participants
SUBUTEX Only	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 SAE other than death	0 Participants
Group 1 (8 mg) RBP-6000: 50 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE	15 Participants
Group 1 (8 mg) RBP-6000: 50 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Deaths	0 Participants
Group 1 (8 mg) RBP-6000: 50 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Withdrew from study due to a TEAE	1 Participants
Group 1 (8 mg) RBP-6000: 50 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE related to study drug	0 Participants
Group 1 (8 mg) RBP-6000: 50 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 SAE other than death	0 Participants
Group 1 (8 mg) RBP-6000: 50 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 Severe TEAE	0 Participants
Group 2 (12 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 SAE other than death	2 Participants
Group 2 (12 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 Severe TEAE	0 Participants
Group 2 (12 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Withdrew from study due to a TEAE	0 Participants
Group 2 (12 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Deaths	0 Participants
Group 2 (12 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE	15 Participants
Group 2 (12 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE related to study drug	0 Participants
Group 3 (24 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 SAE other than death	1 Participants
Group 3 (24 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE	15 Participants
Group 3 (24 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE related to study drug	0 Participants
Group 3 (24 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 Severe TEAE	0 Participants
Group 3 (24 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Deaths	0 Participants
Group 3 (24 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Withdrew from study due to a TEAE	1 Participants
Group 4 (8 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Deaths	0 Participants
Group 4 (8 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE related to study drug	0 Participants
Group 4 (8 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 SAE other than death	1 Participants
Group 4 (8 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Withdrew from study due to a TEAE	2 Participants
Group 4 (8 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 Severe TEAE	0 Participants
Group 4 (8 mg) RBP-6000: 100 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE	15 Participants
Group 5 (14 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 Severe TEAE	1 Participants
Group 5 (14 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Deaths	0 Participants
Group 5 (14 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE related to study drug	0 Participants
Group 5 (14 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 SAE other than death	2 Participants
Group 5 (14 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE	15 Participants
Group 5 (14 mg) RBP-6000: 200 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Withdrew from study due to a TEAE	2 Participants
Group 6 (8-24 mg) RBP-6000: 300 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 Severe TEAE	0 Participants
Group 6 (8-24 mg) RBP-6000: 300 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE related to study drug	0 Participants
Group 6 (8-24 mg) RBP-6000: 300 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Withdrew from study due to a TEAE	2 Participants
Group 6 (8-24 mg) RBP-6000: 300 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	Deaths	0 Participants
Group 6 (8-24 mg) RBP-6000: 300 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 SAE other than death	0 Participants
Group 6 (8-24 mg) RBP-6000: 300 mg	Participants With Treatment-Emergent Adverse Events (TEAEs)	>=1 TEAE	14 Participants

Secondary

Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141

The CGI-I is a 7-item scale completed by the clinician used to rate their impression of how much the participant has improved over a baseline state. The total range is 1 (very much improved) to 7 (very much worse). Baseline was defined as value from Day 1. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing (not applicable for Day 7) and reported as change from baseline values. Negative change from baseline values indicate an improvement.

Time frame: Baseline (Day 1), Days 7, 29, 57, 85, 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter. One participant from Group 6 did not have a baseline evaluation.

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 85	-2.18 units on a scale	Standard Deviation 0.603
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 7	-1.00 units on a scale	Standard Deviation 1.095
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 57	-2.08 units on a scale	Standard Deviation 0.793
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 29	-1.67 units on a scale	Standard Deviation 0.976
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Baseline (observed values)	4.0 units on a scale	Standard Deviation 0
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 7	-0.73 units on a scale	Standard Deviation 0.905
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 57	-1.79 units on a scale	Standard Deviation 0.975
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 85	-2.00 units on a scale	Standard Deviation 0.953
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Baseline (observed values)	4.1 units on a scale	Standard Deviation 0.26
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 29	-1.07 units on a scale	Standard Deviation 1.072
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Baseline (observed values)	4.0 units on a scale	Standard Deviation 0
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 29	-1.77 units on a scale	Standard Deviation 1.092
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 85	-2.73 units on a scale	Standard Deviation 0.467
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 57	-2.36 units on a scale	Standard Deviation 0.809
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 7	-1.42 units on a scale	Standard Deviation 1.084
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 29	-1.69 units on a scale	Standard Deviation 0.947
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 85	-2.60 units on a scale	Standard Deviation 0.699
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 57	-2.17 units on a scale	Standard Deviation 0.937
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Baseline (observed values)	4.0 units on a scale	Standard Deviation 0
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 57	-2.15 units on a scale	Standard Deviation 0.801
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 85	-2.73 units on a scale	Standard Deviation 0.647
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 141	-2.67 units on a scale	Standard Deviation 0.577
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 29	02.07 units on a scale	Standard Deviation 0.616
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Baseline (observed values)	4.0 units on a scale	Standard Deviation 0
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 141	-2.50 units on a scale	Standard Deviation 0.707
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Baseline (observed values)	4.0 units on a scale	Standard Deviation 0
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 29	-2.27 units on a scale	Standard Deviation 1.191
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 57	-2.40 units on a scale	Standard Deviation 0.966
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141	Day 85	-2.57 units on a scale	Standard Deviation 0.787

Secondary

Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141

The CGI-S is a 7-item scale completed by the clinician used to rate the severity of symptoms. The total range is 1 (normal, not at all ill) to 7 (most extremely ill). Baseline was defined as value from screening (Day -13). The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing (not applicable for Day 7) and reported as change from baseline values. Negative change from baseline values indicate a lessening of the severity of symptoms.

Time frame: Baseline (screening Day -15), Days 1, 7, 29, 57, 85, 141

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 7	-1.00 units on a scale	Standard Deviation 1.095
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 29	-1.40 units on a scale	Standard Deviation 1.056
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 85	-1.82 units on a scale	Standard Deviation 0.751
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 1	0.00 units on a scale	Standard Deviation 0
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 57	-1.75 units on a scale	Standard Deviation 1.055
SUBUTEX Only	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Baseline (observed values)	4.3 units on a scale	Standard Deviation 0.49
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 29	-1.00 units on a scale	Standard Deviation 1.038
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 7	-0.50 units on a scale	Standard Deviation 0.527
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 85	-1.83 units on a scale	Standard Deviation 1.115
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 1	0.00 units on a scale	Standard Deviation 0
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Baseline (observed values)	4.3 units on a scale	Standard Deviation 0.61
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 57	-1.29 units on a scale	Standard Deviation 1.204
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 29	-1.23 units on a scale	Standard Deviation 0.927
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Baseline (observed values)	4.4 units on a scale	Standard Deviation 0.51
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 1	0.13 units on a scale	Standard Deviation 0.352
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 7	-1.25 units on a scale	Standard Deviation 0.965
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 57	-1.91 units on a scale	Standard Deviation 1.221
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 85	-2.18 units on a scale	Standard Deviation 0.874
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 29	-1.38 units on a scale	Standard Deviation 0.961
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 57	-1.83 units on a scale	Standard Deviation 1.115
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 1	0.00 units on a scale	Standard Deviation 0
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Baseline (observed values)	4.6 units on a scale	Standard Deviation 0.51
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 85	-2.30 units on a scale	Standard Deviation 1.16
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 1	0.00 units on a scale	Standard Deviation 0
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 29	-1.64 units on a scale	Standard Deviation 0.929
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 141	-3.00 units on a scale	Standard Deviation 1
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 57	-2.00 units on a scale	Standard Deviation 1
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Baseline (observed values)	4.7 units on a scale	Standard Deviation 0.72
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 85	-2.64 units on a scale	Standard Deviation 1.12
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 141	-2.00 units on a scale	Standard Deviation 2.828
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Baseline (observed values)	4.6 units on a scale	Standard Deviation 0.51
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 29	-1.91 units on a scale	Standard Deviation 1.044
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 85	-2.86 units on a scale	Standard Deviation 1.345
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 1	0.00 units on a scale	Standard Deviation 0
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141	Day 57	-2.50 units on a scale	Standard Deviation 1.269

Secondary

Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6

COWS is an 11-item instrument used to assess symptoms of opioid withdrawal (Wesson et al., 1999). The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderate/severe withdrawal, and 37-48 severe withdrawal. Each participant was to be assessed by the same qualified and trained individuals throughout the course of the study as much as possible. Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of withdrawal symptoms.

Time frame: Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter.

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-16.53 units on a scale	Standard Deviation 3.335
SUBUTEX Only	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-18.09 units on a scale	Standard Deviation 3.015
SUBUTEX Only	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-16.67 units on a scale	Standard Deviation 3.155
SUBUTEX Only	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-17.75 units on a scale	Standard Deviation 3.108
SUBUTEX Only	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	17.6 units on a scale	Standard Deviation 3.18
SUBUTEX Only	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-16.80 units on a scale	Standard Deviation 2.908
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-16.79 units on a scale	Standard Deviation 3.262
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	17.7 units on a scale	Standard Deviation 3.22
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-16.33 units on a scale	Standard Deviation 4.152
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-16.73 units on a scale	Standard Deviation 3.788
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-16.62 units on a scale	Standard Deviation 3.776
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-17.08 units on a scale	Standard Deviation 3.895
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	20.4 units on a scale	Standard Deviation 4.42
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-19.33 units on a scale	Standard Deviation 4.67
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-18.91 units on a scale	Standard Deviation 4.253
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-19.55 units on a scale	Standard Deviation 4.059
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-19.27 units on a scale	Standard Deviation 4.891
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-19.92 units on a scale	Standard Deviation 4.663
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-15.77 units on a scale	Standard Deviation 3.059
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-15.60 units on a scale	Standard Deviation 2.72
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	16.2 units on a scale	Standard Deviation 2.91
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-16.08 units on a scale	Standard Deviation 2.937
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-15.50 units on a scale	Standard Deviation 2.324
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-16.10 units on a scale	Standard Deviation 2.998
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 141	-19.67 units on a scale	Standard Deviation 4.041
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-16.87 units on a scale	Standard Deviation 3.563
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	17.9 units on a scale	Standard Deviation 3.65
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-16.71 units on a scale	Standard Deviation 3.989
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-17.62 units on a scale	Standard Deviation 3.453
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-18.00 units on a scale	Standard Deviation 3.873
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-16.80 units on a scale	Standard Deviation 3.986
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 141	-18.00 units on a scale	Standard Deviation 4.243
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	16.7 units on a scale	Standard Deviation 2.33
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-16.36 units on a scale	Standard Deviation 2.341
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-15.93 units on a scale	Standard Deviation 2.056
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-16.00 units on a scale	Standard Deviation 2.828
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-17.00 units on a scale	Standard Deviation 2.449
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-16.91 units on a scale	Standard Deviation 2.548

Secondary

Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6

The Total Score was the sum of 10 questions regarding cravings each ranging from 0 (no craving) - 10 (extreme craving) for a total range from 0 (no cravings) to 100 (most intense craving I have ever had). Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of craving symptoms.

Time frame: Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter.

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day -1	-84.00 units on a scale	Standard Deviation 10.569
SUBUTEX Only	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 85	-84.91 units on a scale	Standard Deviation 12.136
SUBUTEX Only	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 1	-84.47 units on a scale	Standard Deviation 10.569
SUBUTEX Only	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 57	-84.42 units on a scale	Standard Deviation 11.437
SUBUTEX Only	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	85.6 units on a scale	Standard Deviation 9.98
SUBUTEX Only	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 29	-81.73 units on a scale	Standard Deviation 15.975
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 29	-85.00 units on a scale	Standard Deviation 12.247
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	89.7 units on a scale	Standard Deviation 10.13
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day -1	-86.93 units on a scale	Standard Deviation 14.255
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 1	-88.20 units on a scale	Standard Deviation 11.027
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 57	-86.64 units on a scale	Standard Deviation 11.167
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 85	-84.92 units on a scale	Standard Deviation 13.507
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	87.2 units on a scale	Standard Deviation 10.41
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day -1	-84.53 units on a scale	Standard Deviation 11.141
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 57	-86.36 units on a scale	Standard Deviation 11.792
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 85	-86.55 units on a scale	Standard Deviation 11.725
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 1	-84.40 units on a scale	Standard Deviation 11.451
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 29	-85.31 units on a scale	Standard Deviation 11.272
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 29	-83.46 units on a scale	Standard Deviation 8.771
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 1	-83.73 units on a scale	Standard Deviation 8.293
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	86.0 units on a scale	Standard Deviation 7.67
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 57	-82.08 units on a scale	Standard Deviation 9.229
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day -1	-83.33 units on a scale	Standard Deviation 8.449
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 85	-85.70 units on a scale	Standard Deviation 6.848
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 141	-85.33 units on a scale	Standard Deviation 1.528
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 1	-83.00 units on a scale	Standard Deviation 12.689
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	85.1 units on a scale	Standard Deviation 12.64
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 29	-82.36 units on a scale	Standard Deviation 14.836
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 57	-83.85 units on a scale	Standard Deviation 13.459
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 85	-89.27 units on a scale	Standard Deviation 7.157
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day -1	-82.07 units on a scale	Standard Deviation 12.975
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 141	-85.00 units on a scale	Standard Deviation 4.243
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	87.4 units on a scale	Standard Deviation 11.56
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 1	-85.36 units on a scale	Standard Deviation 11.263
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day -1	-85.21 units on a scale	Standard Deviation 11.088
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 85	-87.14 units on a scale	Standard Deviation 11.668
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 57	-88.10 units on a scale	Standard Deviation 10.482
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6	Day 29	-88.45 units on a scale	Standard Deviation 10.377

Secondary

Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6

The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the participant rates on a scale of 0 (not at all) to 4 (extremely) for a full scale of 0 (no withdrawal symptoms) to 64 (extreme withdrawal symptoms). Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of withdrawal symptoms.

Time frame: Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter.

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-38.07 units on a scale	Standard Deviation 11.145
SUBUTEX Only	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-38.36 units on a scale	Standard Deviation 11.595
SUBUTEX Only	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-38.73 units on a scale	Standard Deviation 11.285
SUBUTEX Only	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-39.50 units on a scale	Standard Deviation 11.844
SUBUTEX Only	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	40.2 units on a scale	Standard Deviation 11.14
SUBUTEX Only	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-38.20 units on a scale	Standard Deviation 12.616
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-45.64 units on a scale	Standard Deviation 16.832
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	47.8 units on a scale	Standard Deviation 14.65
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-45.20 units on a scale	Standard Deviation 16.794
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-45.60 units on a scale	Standard Deviation 16.106
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-46.07 units on a scale	Standard Deviation 16.717
Group 1 (8 mg) RBP-6000: 50 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-45.58 units on a scale	Standard Deviation 16.654
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	45.1 units on a scale	Standard Deviation 11.89
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-43.40 units on a scale	Standard Deviation 12.385
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-43.09 units on a scale	Standard Deviation 11.631
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-43.82 units on a scale	Standard Deviation 11.763
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-43.47 units on a scale	Standard Deviation 12.489
Group 2 (12 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-44.15 units on a scale	Standard Deviation 11.689
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-40.62 units on a scale	Standard Deviation 13.997
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-40.80 units on a scale	Standard Deviation 13.624
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	42.7 units on a scale	Standard Deviation 13.8
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-39.50 units on a scale	Standard Deviation 13.945
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-40.67 units on a scale	Standard Deviation 13.563
Group 3 (24 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-41.60 units on a scale	Standard Deviation 14.819
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 141	-45.67 units on a scale	Standard Deviation 5.132
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-39.67 units on a scale	Standard Deviation 15.041
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	42.1 units on a scale	Standard Deviation 15.41
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-39.64 units on a scale	Standard Deviation 15.979
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-38.85 units on a scale	Standard Deviation 15.486
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-41.27 units on a scale	Standard Deviation 15.691
Group 4 (8 mg) RBP-6000: 100 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-39.47 units on a scale	Standard Deviation 16.048
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 141	-59.50 units on a scale	Standard Deviation 6.364
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Baseline (observed values)	43.9 units on a scale	Standard Deviation 16.2
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 1	-42.57 units on a scale	Standard Deviation 16.603
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day -1	-42.71 units on a scale	Standard Deviation 17.117
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 85	-51.71 units on a scale	Standard Deviation 13.793
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 57	-49.20 units on a scale	Standard Deviation 12.77
Group 5 (14 mg) RBP-6000: 200 mg	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6	Day 29	-46.00 units on a scale	Standard Deviation 15.205

Secondary

Columbia Suicide Severity Rating Scale (C-SSRS): Severity

The scale used in the C-SSRS is a continuous variable ranging from 0 (no suicidal ideation present) to 5 (active ideation with specific plan and intent). Only participants with suicidal ideation (scale of 1-5) are reported. 1=desire to be dead to 5=active ideation with specific plan and intent.

Time frame: Screening (summary of lifetime), Screening (last 6 months), Day 65, Day 113, End of Study (up to day 365)

Population: PD population

Arm	Measure	Group	Value (MEAN)	Dispersion
SUBUTEX Only	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Screening (summary of lifetime)	1.0 units on a scale	—
Group 1 (8 mg) RBP-6000: 50 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Day 113	1.0 units on a scale	—
Group 2 (12 mg) RBP-6000: 100 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	End of study	5.0 units on a scale	—
Group 2 (12 mg) RBP-6000: 100 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Screening (summary of lifetime)	1.8 units on a scale	Standard Deviation 0.45
Group 3 (24 mg) RBP-6000: 200 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Screening (summary of lifetime)	2.0 units on a scale	Standard Deviation 1.41
Group 4 (8 mg) RBP-6000: 100 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Screening (summary of lifetime)	1.0 units on a scale	—
Group 4 (8 mg) RBP-6000: 100 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Day 65	1.0 units on a scale	—
Group 5 (14 mg) RBP-6000: 200 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Screening (summary of lifetime)	1.3 units on a scale	Standard Deviation 0.58
Group 5 (14 mg) RBP-6000: 200 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Screening (last 6 months)	1.0 units on a scale	—
Group 5 (14 mg) RBP-6000: 200 mg	Columbia Suicide Severity Rating Scale (C-SSRS): Severity	Day 65	1.0 units on a scale	—

Secondary

Percentage of Urine Drug Screen Samples Negative for Opioids

Urine samples were screened for the following drugs: * opiates * cocaine * amphetamines * methadone * cannabinoids * barbiturates * buprenorphine. Buprenorphine was only included in the urine drug screen at screening and Day -14 to determine if the subject had used any buprenorphine-containing products prior to the start of SUBUTEX SL tablet dosing. * benzodiazepines * methamphetamine * phencyclidine Urine drug screens were run every day when the participant was an inpatient; every 2-3 days when the participant was an outpatient. Drug screens were run less often for those participants in the PET substudy.

Time frame: Day 1 to End of Study (up to day 365)

Population: Safety population

Arm	Measure	Value (MEAN)	Dispersion
SUBUTEX Only	Percentage of Urine Drug Screen Samples Negative for Opioids	41.2 percentage of total urine drug samples	Standard Deviation 32.89
Group 1 (8 mg) RBP-6000: 50 mg	Percentage of Urine Drug Screen Samples Negative for Opioids	42.0 percentage of total urine drug samples	Standard Deviation 35.43
Group 2 (12 mg) RBP-6000: 100 mg	Percentage of Urine Drug Screen Samples Negative for Opioids	54.6 percentage of total urine drug samples	Standard Deviation 23.98
Group 3 (24 mg) RBP-6000: 200 mg	Percentage of Urine Drug Screen Samples Negative for Opioids	49.9 percentage of total urine drug samples	Standard Deviation 25.53
Group 4 (8 mg) RBP-6000: 100 mg	Percentage of Urine Drug Screen Samples Negative for Opioids	41.6 percentage of total urine drug samples	Standard Deviation 27.68
Group 5 (14 mg) RBP-6000: 200 mg	Percentage of Urine Drug Screen Samples Negative for Opioids	64.9 percentage of total urine drug samples	Standard Deviation 23.56

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Multiple Dose Pharmacokinetics Depot Buprenorphine in Opioid-Dependent Subjects

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))

Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))

Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6

Buprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 (AUC0-∞)

Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)

Buprenorphine PK: Average Plasma Concentration (Cavg)

Buprenorphine PK: % Fluctuation

Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax)

Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin)

Buprenorphine PK: Swing of Plasma Concentrations

Buprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4

Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)

Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))

Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))

Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞)

Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC)

Norbuprenorphine PK: Average Plasma Concentration (Cavg)

Norbuprenorphine PK: % Fluctuation

Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax)

Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin)

Norbuprenorphine PK: Swing of Plasma Concentrations

Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4

Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax)

Participants With Treatment-Emergent Adverse Events (TEAEs)

Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141

Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141

Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6

Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6

Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6

Columbia Suicide Severity Rating Scale (C-SSRS): Severity

Percentage of Urine Drug Screen Samples Negative for Opioids