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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.
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| (8 mg) RBP-6000: 50 mg | Experimental | Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals. |
|
| (12 mg) RBP-6000: 100 mg | Experimental | Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals |
|
| (24 mg) RBP-6000: 200 mg | Experimental | Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who receive RBP-6000 containing 200 mg buprenorphine and reach Day 112 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection. |
|
| (8 mg) RBP-6000: 100 mg | Experimental | Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RBP-6000 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Days -14 to -1 (Subutex treatment), Days 1-316 (RBP-6000 treatment) |
| 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:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| 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:
The PK sampling schedule was
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bradley D Vince, DO | Vince and Associates Clinical Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vince and Associates Clinical Research | Overland Park | Kansas | 66212 | United States |
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | SUBUTEX | Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL. Those who did not complete this period, did not continue into the Treatment period. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Induction/Stabilization (Days -14 to -1) |
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| Treatment Period |
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| PET Imaging Sub-study |
|
Safety population
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Group 2 (12 mg) RBP-6000: 100 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Safety analysis group | Posted | Count of Participants | Participants | Days -14 to -1 (Subutex treatment), Days 1-316 (RBP-6000 treatment) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SUBUTEX Only | Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lobar pneumonia | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Director, Clinical Development | Indivior, Inc. | 804-379-1090 |
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| (14 mg) RBP-6000: 200 mg | Experimental | Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who receive RBP-6000 containing 200 mg buprenorphine and reach Day 112 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection. |
|
| (8-24 mg) RBP-6000: 300 mg | Experimental | Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. |
|
|
| Subutex | Drug | Participants were inducted and stabilized over a 14-day period (study days -14 to -1) on SUBUTEX sublingual tablets. Tablets are placed under the tongue until dissolved. |
|
|
| Day -1, Days 1-29, 85-113, 141-197 |
| 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:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentration, determined directly from individual concentration time data. Results are reported across four timeframes:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) | Minimum observed plasma concentration, determined directly from individual concentration time data. Results are reported across three timeframes:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| 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:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) | Results are reported across four timeframes:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| 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). | Days 1-28, 85-113 |
| 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. | Days 1-28, 85-113 |
| 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). | Days 85-113, 141-169 |
| 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. | Days 85-113 |
| 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. | Days 85-113 |
| 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:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Norbuprenorphine 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:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Norbuprenorphine 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:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentration, determined directly from individual concentration time data. Results are reported across four timeframes:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) | Minimum observed plasma concentration, determined directly from individual concentration time data. Results are reported across three timeframes:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| 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:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) | Results are reported across four timeframes:
The PK sampling schedule was
| Day -1, Days 1-29, 85-113, 141-197 |
| Norbuprenorphine 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). | Days 1-28, 85-113 |
| 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. | Days 1-28, 85-113 |
| 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. | Days 85-113, 141-197 |
| 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. | Days 85-113, 141-197 |
| Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141 |
| 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. | Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141 |
| 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. | Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141 |
| 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. | Baseline (screening Day -15), Days 1, 7, 29, 57, 85, 141 |
| 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. | Baseline (Day 1), Days 7, 29, 57, 85, 141 |
| 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. | Screening (summary of lifetime), Screening (last 6 months), Day 65, Day 113, End of Study (up to day 365) |
| Percentage of Urine Drug Screen Samples Negative for Opioids | Urine samples were screened for the following drugs:
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. | Day 1 to End of Study (up to day 365) |
| COMPLETED |
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| NOT COMPLETED |
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|
| COMPLETED |
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| NOT COMPLETED |
|
|
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 |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Height | Mean | Standard Deviation | cm |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Other Opioid Use | Missing participants reported no use | Mean | Standard Deviation | years |
|
| Heroin Use | Missing participants reported no use | Mean | Standard Deviation | years |
|
| Smoking History (Nicotine Use) | Missing participants reported no use | Mean | Standard Deviation | years |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | SUBUTEX Only | Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period. |
| OG001 | 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. |
| OG002 | 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 |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | % of average concentration | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | hr*ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | percentage of Cmin | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| Primary | Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) | Results are reported across four timeframes:
The PK sampling schedule was
| 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. | Posted | Median | Full Range | hours | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| 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). | PK population of participants with data at both timepoints | Posted | Mean | Standard Deviation | ratio | Days 1-28, 85-113 |
|
|
|
| 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. | PK population of participants with data at both timepoints | Posted | Mean | Standard Deviation | ratio | Days 1-28, 85-113 |
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|
|
| 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). | PK population | Posted | Mean | Standard Deviation | L/hour | Days 85-113, 141-169 |
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|
|
| 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. | PK population of participants whose data met requirements. | Posted | Mean | Standard Deviation | hr*ng/mL | Days 85-113 |
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|
|
| 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. | PK population of participants whose data met requirements. | Posted | Mean | Standard Deviation | hours | Days 85-113 |
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|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | % of average concentration | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| Primary | Norbuprenorphine 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | hr*ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| Primary | Norbuprenorphine 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| Primary | Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentration, determined directly from individual concentration time data. Results are reported across four timeframes:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| Primary | Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) | Minimum observed plasma concentration, determined directly from individual concentration time data. Results are reported across three timeframes:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | ng/mL | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| 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:
The PK sampling schedule was
| 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. | Posted | Mean | Standard Deviation | percentage of Cmin | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| Primary | Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) | Results are reported across four timeframes:
The PK sampling schedule was
| 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. | Posted | Median | Full Range | hours | Day -1, Days 1-29, 85-113, 141-197 |
|
|
|
| Primary | Norbuprenorphine 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). | PK population of participants with data at both timepoints | Posted | Mean | Standard Deviation | ratio | Days 1-28, 85-113 |
|
|
|
| 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. | PK population of participants with data at both timepoints | Posted | Mean | Standard Deviation | ratio | Days 1-28, 85-113 |
|
|
|
| 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. | PK population of participants whose data met requirements. | Posted | Mean | Standard Deviation | hr*ng/mL | Days 85-113, 141-197 |
|
|
|
| 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. | PK population of participants whose data met requirements. | Posted | Mean | Standard Deviation | hours | Days 85-113, 141-197 |
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|
|
| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141 |
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|
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141 |
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| 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. | 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 2 did not have a baseline evaluation. | Posted | Mean | Standard Deviation | units on a scale | Baseline (screening Day -15), Days 1, 7, 29, 57, 85, 141 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline (Day 1), Days 7, 29, 57, 85, 141 |
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| 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. | PD population | Posted | Mean | Standard Deviation | units on a scale | Screening (summary of lifetime), Screening (last 6 months), Day 65, Day 113, End of Study (up to day 365) |
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| Secondary | Percentage of Urine Drug Screen Samples Negative for Opioids | Urine samples were screened for the following drugs:
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. | Safety population | Posted | Mean | Standard Deviation | percentage of total urine drug samples | Day 1 to End of Study (up to day 365) |
|
|
|
| 0 |
| 35 |
| 0 |
| 35 |
| 24 |
| 35 |
| EG001 | 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. | 0 | 15 | 0 | 15 | 15 | 15 |
| EG002 | 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 | 0 | 15 | 2 | 15 | 15 | 15 |
| EG003 | 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. | 0 | 15 | 1 | 15 | 15 | 15 |
| EG004 | 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. | 0 | 15 | 1 | 15 | 15 | 15 |
| EG005 | 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 112 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection. | 0 | 15 | 2 | 15 | 15 | 15 |
| EG006 | 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. | 0 | 14 | 0 | 14 | 14 | 14 |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Personality disorder | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pelvic inflammatory disease | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Vaginitis bacterial | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
|
| Thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
|
| Granulocytopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Leukoyctosis | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
|
| Atrioventricular block first degree | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (14.1) | Systematic Assessment |
|
| Cerumen impaction | Ear and labyrinth disorders | MedDRA (14.1) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (14.1) | Systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Faeces hard | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Gingivitis | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Drug withdrawal syndrome | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Facial pain | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Irritability | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Inflammation | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Influenza-like illness | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Injection site dermatitis | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Injection site papule | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hepatic cyst | Hepatobiliary disorders | MedDRA (14.1) | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Autoimmune disorder | Immune system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Tinea pedis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Chlamydial infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Infective glossitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Onychomycosis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Perirectal abscess | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Postoperative wound infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Corneal abrasion | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Testicular injury | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Blood creatinine phosphokinase increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Weight fluctuation | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
|
| Thyroid neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
|
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Myoclonus | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Restless leg syndrome | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vomiting in pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (14.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abnormal dreams | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Intentional self-injury | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Panic attack | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Substance-induced mood disorder | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Substance-induced psychotic disorder | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pyuria | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
|
| Urinary hesitation | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Nasal ulcer | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Eczema asteatotic | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Physical assault | Social circumstances | MedDRA (14.1) | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
|
| Bundle branch block right | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Orthostatic hypertension | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
|
Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multi-center publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.
| D006572 |
| Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
| Plateau: Injection 1 |
|
|
| Plateau: Injection 4 |
|
|
| Plateau: Injection 6 |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Initial Burst: Injection 1 (0-48 hours) |
|
|
| Initial Burst: Injection 4 (0-48 hours) |
|
|
| Initial Burst: Injection 6 (0-48 hours) |
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 (0-24 hours) |
|
|
| Overall: Injection 1 (0-28 days) |
|
|
| Overall: Injection 4 (0-24 hours) |
|
|
| Overall: Injection 4 (0-28 days) |
|
|
| Overall: Injection 6 (0-24 hours) |
|
|
| Overall: Injection 6 (0-28 days) |
|
|
|
| Plateau: Injection 1 |
|
|
| Plateau: Injection 4 |
|
|
| Plateau: Injection 6 |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Initial Burst: Injection 1 (0-48 hours) |
|
|
| Initial Burst: Injection 4 (0-48 hours) |
|
|
| Initial Burst: Injection 6 (0-48 hours) |
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Plateau: Injection 1 |
|
|
| Plateau: Injection 4 |
|
|
| Plateau: Injection 6 |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Initial Burst: Injection 1 (0-48 hours) |
|
|
| Initial Burst: Injection 4 (0-48 hours) |
|
|
| Initial Burst: Injection 6 (0-48 hours) |
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 (0-28 days) |
|
|
| Overall: Injection 4 (0-28 days) |
|
|
| Overall: Injection 6 (0-28 days) |
|
|
|
| Injection 6 |
|
|
|
| Plateau: Injection 1 |
|
|
| Plateau: Injection 4 |
|
|
| Plateau: Injection 6 |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Initial Burst: Injection 1 (0-48 hours) |
|
|
| Initial Burst: Injection 4 (0-48 hours) |
|
|
| Initial Burst: Injection 6 (0-48 hours) |
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 (0-24 hours) |
|
|
| Overall: Injection 1 (0-28 days) |
|
|
| Overall: Injection 4 (0-24 hours) |
|
|
| Overall: Injection 4 (0-28 days) |
|
|
| Overall: Injection 6 (0-24 hours) |
|
|
| Overall: Injection 6 (0-28 days) |
|
|
|
| Plateau: Injection 1 |
|
|
| Plateau: Injection 4 |
|
|
| Plateau: Injection 6 |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Initial Burst: Injection 1 (0-48 hours) |
|
|
| Initial Burst: Injection 4 (0-48 hours) |
|
|
| Initial Burst: Injection 6 (0-48 hours) |
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Plateau: Injection 1 |
|
|
| Plateau: Injection 4 |
|
|
| Plateau: Injection 6 |
|
|
| Overall: Injection 1 |
|
|
| Overall: Injection 4 |
|
|
| Overall: Injection 6 |
|
|
|
| Initial Burst: Injection 1 (0-48 hours) |
|
|
| Initial Burst: Injection 4 (0-48 hours) |
|
|
| Initial Burst: Injection 6 (0-48 hours) |
|
|
| Plateau: Injection 1 (2-28 days) |
|
|
| Plateau: Injection 4 (2-28 days) |
|
|
| Plateau: Injection 6 (2-28 days) |
|
|
| Overall: Injection 1 (0-28 days) |
|
|
| Overall: Injection 4 (0-28 days) |
|
|
| Overall: Injection 6 (0-28 days) |
|
|
|
| Overall: Injection 6 (0-28 days) |
|
|
|
| Overall: Injection 6 (0-28 days) |
|
|
|
| Day -1 |
|
|
| Day 1 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 141 |
|
|
|
| Day -1 |
|
|
| Day 1 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 141 |
|
|
|
| Day -1 |
|
|
| Day 1 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 141 |
|
|
|
| Day 1 |
|
|
| Day 7 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 141 |
|
|
|
| Day 7 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 141 |
|
|
|
| Screening (last 6 months) |
|
|
| Day 65 |
|
|
| Day 113 |
|
|
| End of study |
|
|