Back to resultsStudy of a Novel Subcutaneous Depot Formulation of Buprenorphine
Primary Purpose
Opioid-use Disorder
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
INDV-6200
Placebo
SL Buprenorphine
Nalorex
Sponsored by
About this trial
This is an interventional treatment trial for Opioid-use Disorder
Eligibility Criteria
Inclusion Criteria:
- Healthy males or non-pregnant, non-lactating females
- Body mass index of 18.0-33.0 kg/m2 or, if outside the range, considered not clinically significant by the Investigator
- Willing and able to communicate and participate in the whole study
- Provide written informed consent prior to any study specific procedures
- Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment, ECG, and laboratory investigations
- Males and females must agree to use an adequate method of contraception
- Tolerated SL buprenorphine and nalorex during Period 1
Exclusion Criteria:
- Medical history of opioid-related adverse reactions
- History of clinically significant alcohol/drug abuse in the previous 5 years
- Received any investigational medicinal product within the previous 3 months
- Study site employees or immediate family members of study site or sponsor employee
- Previously enrolled in the study
- Regular alcohol consumption in males greater than 21 units/week and females greater than 14 units/week
- Current smokers and those who have smoked within the last 6 months
- Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 6 months
- Do not have suitable veins for multiple venipunctures
- Clinically significant abnormal biochemistry, haematology or urinalysis
- Positive urine drug screen at screening and admission for each period
- Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results
- History of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory, or gastrointestinal disease, or psychiatric disorder
- Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
- Clinically significant allergy requiring treatment. Hayfever is allowed unless active
- Donation or loss of greater than 400 mL of blood within the previous 3 months
- Taking or have taken, any prescribed or over-the counter drugs or herbal remedies in the 14 days before IMP administrations. Exceptions may apply
- Injection sites containing any skin discolouration, tattoo, scar tissue or other abnormalities that may impair injection site assessment
- Any food or drink containing grapefruit or Seville oranges within 7 days prior to first dose of buprenorphine
- Treatment with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) 3A4 and/or cytochrome 450 2C8 enzyme within 30 days prior to first dose of study drug
- Clinically significant abnormal ECG, including QT interval corrected using Fridericia's formula of greater than 450msec in males and greater than 470 msec in females
Sites / Locations
- Quotient Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Depot buprenorphine (INDV-6200)
Placebo
Arm Description
Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive depot buprenorphine
Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive volume-matched placebo
Outcomes
Primary Outcome Measures
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the time of maximum concentration (Tmax) of buprenorphine will be evaluated.
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the maximum concentration (Cmax) of buprenorphine will be evaluated.
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the cumulative area under the curve (AUC) for each PK sample will be evaluated.
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the half life of buprenorphine will be evaluated.
Secondary Outcome Measures
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of Tmax of norbuprenorphine will be evaluated.
Assessment of PK INDV-6200 (norbuprenorphine)
The key parameter of Cmax of norbuprenorphine will be evaluated.
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of the half life of norbuprenorphine will be evaluated
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of the cumulative area under the curve (AUC) for each PK sample will be evaluated.
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in physical examination.
Targeted physical examination will be performed focusing on abnormalities identified at screening and any changes. Clinically significant changes will be reported as adverse events (AE)
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in liver function tests.
Laboratory data will be summarized and any clinically significant abnormality will be reported as an AE
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in systolic and diastolic blood pressure
Blood pressure measurements (systolic and diastolic) will be summarized and any clinically significant abnormality will be reported as an AE
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in heart rate
Heart rate will be summarized and any clinically significant changes will be reported as an AE
Incidence of treatment emergence adverse events (TEAE) as assessed by electrocardiogram (ECG) changes
ECG intervals will be measured and summarized and any clinically significant changes will be reported as an AE
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of erythema
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of erythema will be summarized using counts and percentages at each timepoint by treatment
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of swelling
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of swelling will be summarized using counts and percentages at each timepoint by treatment
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of pain
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of pain will be summarized using counts and percentages at each timepoint by treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03715634
Brief Title
Study of a Novel Subcutaneous Depot Formulation of Buprenorphine
Official Title
A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Novel Subcutaneous Depot Formulation of Buprenorphine (INDV-6200) in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
September 20, 2017 (Actual)
Primary Completion Date
June 7, 2018 (Actual)
Study Completion Date
June 7, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indivior Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
INDV-6200 is being developed for the treatment of opioid dependency and is expected to provide sustained buprenorphine plasma concentrations. The study will be done in healthy volunteers and will administer a non-therapeutic dose of INDV-6200. Study Period 1 will evaluate the oral tolerability of sublingual (SL) buprenorphine dosed over 3 days. Period 2 will administer the investigational medicinal product (IMP) or volume matched placebo.
Detailed Description
INDV-6200 is a novel buprenorphine subcutaneous (SC) depot formulation being developed for the treatment of opioid dependency. It is expected to provide sustained buprenorphine plasma concentrations to achieve consistent and optimal occupancy of mu-opioid receptors in the brain, for the treatment of opioid use disorder. A related subcutaneously injected, extended-release product of buprenorphine base has demonstrated sustained therapeutic plasma levels of buprenorphine over a minimum of 1 month.
Extensive experience gained from RBP-6000 allowed the development of an allometric model which has been used to predict the in vivo performance of INDV-6200. The preclinical pharmacokinetic (PK) data and the predictions from allometric scaling indicate that INDV-6200 is expected to display a similar PK profile as RBP-6000. Therefore, the main objective of this study is to investigate the PK properties of this new, related formulation using a low dose with a large safety margin.
Period 1 will be used to evaluate the oral tolerability of SL buprenorphine (SUBUTEX; non-investigational medicinal product [nIMP]) dosed over 3 days. Period 2 will involve administration of the IMP (INDV-6200) or volume-matched placebo; (low dose in Cohort A or alternative dose in optional Cohort B), to evaluate PK and safety of this novel formulation.
Both periods will also include a series of Nalorex (nIMP) administrations to antagonise potential opioid effects from buprenorphine.
Based on modeling and simulation, the dose proposed for Cohort A is expected to give similar plasma buprenorphine exposure to that obtained with the same SC dose of RBP-6000. If buprenorphine plasma exposure is lower than predicted, there is an optional second cohort (Cohort B), which may be used to explore another dose level of INDV-6200 predicted.
As this is a Phase I study, using a non-therapeutic dose of INDV-6200, the most relevant population is healthy subjects as this allows a characterisation of safety, tolerability and PK for a new molecular entity in a homogeneous population without potential biases from a patient population. In order to avoid any interaction with other medication, no co-medication will be allowed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid-use Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Depot buprenorphine (INDV-6200)
Arm Type
Experimental
Arm Description
Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive depot buprenorphine
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive volume-matched placebo
Intervention Type
Drug
Intervention Name(s)
INDV-6200
Intervention Description
Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo
Intervention Type
Drug
Intervention Name(s)
SL Buprenorphine
Other Intervention Name(s)
Subutex
Intervention Description
All subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability
Intervention Type
Drug
Intervention Name(s)
Nalorex
Intervention Description
Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine
Primary Outcome Measure Information:
Title
Assessment of PK of INDV-6200 (buprenorphine)
Description
The key parameter of the time of maximum concentration (Tmax) of buprenorphine will be evaluated.
Time Frame
84 days
Title
Assessment of PK of INDV-6200 (buprenorphine)
Description
The key parameter of the maximum concentration (Cmax) of buprenorphine will be evaluated.
Time Frame
84 days
Title
Assessment of PK of INDV-6200 (buprenorphine)
Description
The key parameter of the cumulative area under the curve (AUC) for each PK sample will be evaluated.
Time Frame
84 days
Title
Assessment of PK of INDV-6200 (buprenorphine)
Description
The key parameter of the half life of buprenorphine will be evaluated.
Time Frame
84 days
Secondary Outcome Measure Information:
Title
Assessment of PK of INDV-6200 (norbuprenorphine)
Description
The key parameter of Tmax of norbuprenorphine will be evaluated.
Time Frame
84 days
Title
Assessment of PK INDV-6200 (norbuprenorphine)
Description
The key parameter of Cmax of norbuprenorphine will be evaluated.
Time Frame
84 days
Title
Assessment of PK of INDV-6200 (norbuprenorphine)
Description
The key parameter of the half life of norbuprenorphine will be evaluated
Time Frame
84 days
Title
Assessment of PK of INDV-6200 (norbuprenorphine)
Description
The key parameter of the cumulative area under the curve (AUC) for each PK sample will be evaluated.
Time Frame
84 days
Title
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in physical examination.
Description
Targeted physical examination will be performed focusing on abnormalities identified at screening and any changes. Clinically significant changes will be reported as adverse events (AE)
Time Frame
Through day 84
Title
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in liver function tests.
Description
Laboratory data will be summarized and any clinically significant abnormality will be reported as an AE
Time Frame
Through day 84
Title
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in systolic and diastolic blood pressure
Description
Blood pressure measurements (systolic and diastolic) will be summarized and any clinically significant abnormality will be reported as an AE
Time Frame
Through day 84
Title
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in heart rate
Description
Heart rate will be summarized and any clinically significant changes will be reported as an AE
Time Frame
Through day 84
Title
Incidence of treatment emergence adverse events (TEAE) as assessed by electrocardiogram (ECG) changes
Description
ECG intervals will be measured and summarized and any clinically significant changes will be reported as an AE
Time Frame
Through day 84
Title
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of erythema
Description
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of erythema will be summarized using counts and percentages at each timepoint by treatment
Time Frame
Through day 84
Title
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of swelling
Description
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of swelling will be summarized using counts and percentages at each timepoint by treatment
Time Frame
Through day 84
Title
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of pain
Description
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of pain will be summarized using counts and percentages at each timepoint by treatment
Time Frame
Through day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy males or non-pregnant, non-lactating females
Body mass index of 18.0-33.0 kg/m2 or, if outside the range, considered not clinically significant by the Investigator
Willing and able to communicate and participate in the whole study
Provide written informed consent prior to any study specific procedures
Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment, ECG, and laboratory investigations
Males and females must agree to use an adequate method of contraception
Tolerated SL buprenorphine and nalorex during Period 1
Exclusion Criteria:
Medical history of opioid-related adverse reactions
History of clinically significant alcohol/drug abuse in the previous 5 years
Received any investigational medicinal product within the previous 3 months
Study site employees or immediate family members of study site or sponsor employee
Previously enrolled in the study
Regular alcohol consumption in males greater than 21 units/week and females greater than 14 units/week
Current smokers and those who have smoked within the last 6 months
Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 6 months
Do not have suitable veins for multiple venipunctures
Clinically significant abnormal biochemistry, haematology or urinalysis
Positive urine drug screen at screening and admission for each period
Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results
History of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory, or gastrointestinal disease, or psychiatric disorder
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Clinically significant allergy requiring treatment. Hayfever is allowed unless active
Donation or loss of greater than 400 mL of blood within the previous 3 months
Taking or have taken, any prescribed or over-the counter drugs or herbal remedies in the 14 days before IMP administrations. Exceptions may apply
Injection sites containing any skin discolouration, tattoo, scar tissue or other abnormalities that may impair injection site assessment
Any food or drink containing grapefruit or Seville oranges within 7 days prior to first dose of buprenorphine
Treatment with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) 3A4 and/or cytochrome 450 2C8 enzyme within 30 days prior to first dose of study drug
Clinically significant abnormal ECG, including QT interval corrected using Fridericia's formula of greater than 450msec in males and greater than 470 msec in females
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nand Singh
Organizational Affiliation
Quotient Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Quotient Sciences
City
Ruddington
State/Province
Nottingham
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of a Novel Subcutaneous Depot Formulation of Buprenorphine
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