Maintenance/substitution agent for the treatment of opioid dependence. MedDRA version: 14.1 Level: LLT Classification code 10012346 Term: Dependence on opiates System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: Buprenorphine hemiadipate hydrochloride 5mg / Naloxone hydrochloride dihydrate 5mg
Pharmaceutical Form: Injection
INN or Proposed INN: Buprenorphine hemiadipate hydrochloride
Current Spo
Sponsors
RB Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be male or non-pregnant, non-lactating females. 2. Subjects must be at least 18 years of age. 3. Subjects must provide written informed consent and must be willing that their general practitioners be notified of their participation in the study. 4. Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 3 months after the last dose of study drug. Women of childbearing potential are defined as all women who have not had a complete surgical hysterectomy or who cannot be documented as being at least 1 year postmenopausal. Medically acceptable forms of birth control include oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed more than 1 year before screening), or double-barrier contraception. 5. Subjects must be able to communicate well with the investigator, understand and comply with the requirements of the study, and understand the written informed consent. 6. Subjects must meet Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria for opioid dependence at screening. 7. Self reported use of opioids for 15 of the past 28 days, with self reported use spanning the last 6 months. 8. Positive urine screen for opioids. 9. Subjects seeking treatment for opioid dependence or currently being treated with buprenorphine but continuing to inject opioids 3 times per week. 10. Female subjects of childbearing potential must have a negative urine ß-hCG test prior to enrolment into the study. 11. Weight within 15% of ideal body weight according to current actuarial tables. 12. No active illness as determined by history, physical examination, electrocardiogram and clinical laboratory tests. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects who are unwilling or unable to comply with the requirements of the protocol or who are in a situation or have a condition that, in the opinion of the investigator, may interfere with participation in the study. 2. Self reported use of methadone in the 30 days prior to the screening visit. 3. Subjects who, within 2 months prior to signing the informed consent document, participated in any other clinical study in which medications were delivered or who plan to participate in any other clinical study prior to the follow-up visit of the present trial. 4. Subjects with known allergy or sensitivity to buprenorphine or naloxone or to any of the excipients of Subutex®/Suboxone® or RBP-6300. 5. Subjects who are staff personnel or are affiliated with or a family member of staff personnel directly involved in the study. 6. Subjects with serious untreated Axis I DSM-IV-TR psychiatric co-morbidity (for example, those who are actively suicidal or have untreated schizophrenia). 7. Subjects with significant benzodiazepine use requiring medical detoxification or alcohol dependence requiring medical detoxification. Current polysubstance abuse or dependence is not a reason for exclusion. 8. Subjects with a current diagnosis of chronic pain requiring opioid treatment. 9. Subjects with an ECG result that shows a repeated demonstration of a QTc interval >450ms or a history of risk factors of Torsades de Pointes (eg heart failure, hypokalemia, family history of Long QT Syndrome) 10. Subjects with aspartate aminotransferase (AST) levels =3 × upper limit of normal (ULN), alanine aminotransferase (ALT) levels =3 × ULN, or total bilirubin levels =1.5 × ULN. 11. Subjects with uncontrolled medical or psychiatric illness. 12. Subjects currently using opioid treatment (except buprenorphine), other opioid derivatives (e.g., methadone and analgesics), clonidine and related substances and clinically relevant CYP3A4 inhibitors or inducers. 13. Subjects positive for human immunodeficiency virus (HIV), or showing evidence of acute hepatitis B or C infection—acute infection is defined assubjects positive for hepatitis B surface antigen (HBsAg) and immunoglobulin M antibodies to hepatitis B core antigen (anti-HBc IgM), and those with clinical evidence of either acute hepatitis B infection or acute hepatitis C infection.Subjects with chronic active hepatitis should also be excluded Subjects with asymptomatic hepatitis B or C infection and those asymptomatic currently being treated may be enrolled. 14. Subjects for whom treatment with Subutex®/Suboxone® is a contraindication as per the Summary of Product Characteristics (SmPC), such as subjects with severe respiratory insufficiency or severe hepatic insufficiency.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the behavioural and physiological effects of injecting buprenorphine hemiadipate hydrochloride (HCl)/naloxone HCl dihydrate both alone and in combination at three different dose ratios 1:1, 1:0.5 and 1:0.25, with placebo. ;Secondary Objective: To evaluate the safety and tolerability of injecting buprenorphine HCl, diamorphine andbuprenorphine hemiadipate HCl/naloxone HCl dihydrate both alone and in combination (at three different dose ratios 1:1, 1:0.5 1:0.25).;Primary end point(s): The primary efficacy end point will be the mean change in the COWS from baseline (i.e. pre-challenge) over 60 minutes post-challenge.;Timepoint(s) of evaluation of this end point: The COWS scores will be summarised by assessment (baseline [10 minutes prechallenge] and 5, 15, 30, 45 and 60 minutes post-challenge) and challenge (A to H) using number of subjects, mean, standard deviation, median, minimum and maximum values. The mean COWS scores for each challenge will be plotted by assessment. The change from baseline COWS scores will also be summarised by post-baseline assessment and challenge using number of subjects, mean, standard deviation, median, minimum and maximum values, and the 95% confidence interval for the mean. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following secondary endpoints will be analysed using the same(or appropriate similar) statistical methods as those for the primary endpoint: • Change from baseline COWS scores for all post-baseline assessments up to and including the 300 minute assessment • Change from baseline COWS scores for each post-baseline assessment (5, 15, 30, 45, 60, 120, 180, 240 and 300 minutes post-challenge) • VAS-G , VAS-B and VAS-high scores for all post-baseline assessments up to and including the 60 minute assessment • VAS-G , VAS-B and VAS-high scores for all post-baseline assessments up to and including the 300 minute assessment • VAS-G , VAS-B and VAS-high scores for each post-baseline assessment (5, 15, 30, 45, 60, 120, 180, 240 and 300 minutes post-challenge) • Change from baseline for each of the AEC item scores for all post-baseline assessments up to and including the 60 minute assessment • Change from baseline for each of the AEC item scores for all post-baseline assessments up to and including the 300 minute assessment • Change from baseline for each of the AEC item scores for each post-baseline assessment (5, 15, 30, 45, 60, 120, 180, 240 and 300 minutes post-challenge);Timepoint(s) of evaluation of this end point: For each endpoint the scores will be summarised by assessment (baseline [10 minutes pre-challenge] and 5, 15, 30, 45, 60, 120, 180, 240 and 300 minutes post-challenge) and challenge (A to H) using number of subjects, mean, standard deviation, median, minimum and maximum values. The mean scores for each challenge will be plotted by assessment. For each endpoint (where appropriate) the change from baseline scores will also be summarised by post-baseline assessment and challenge using number of subjects, mean, standard deviation, median, minimum and maximum values, and the 95% confidence interval for the mean. | — |
Countries
United Kingdom
Contacts
Public ContactMark Hood
RB Pharmaceuticals Inc
Outcome results
None listed