Opioid-use DisorderPhase 1NCT03715634
Study of a Novel Subcutaneous Depot Formulation of Buprenorphine
A Phase 1 study testing INDV-6200, SL Buprenorphine and Nalorex in people with Opioid-use Disorder, run by Indivior Inc. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid-use Disorder
- What is being tested?
- INDV-6200, SL Buprenorphine and Nalorex
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Sep 2017to 7 Jun 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Novel Subcutaneous Depot Formulation of Buprenorphine (INDV-6200) in Healthy Volunteers
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.
Read the 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.
- Conditions
- Opioid-use Disorder
- Being tested
- INDV-6200, Placebo, SL Buprenorphine, Nalorex
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INDV-6200Drug
Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo
PlaceboDrug
Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo
SL BuprenorphineDrug
Also called Subutex
All subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability
NalorexDrug
Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine
| Study group | Role | What they receive |
|---|---|---|
| Depot buprenorphine (INDV-6200) | Experimental | Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive depot buprenorphine Receives: Drug: INDV-6200; Drug: SL Buprenorphine; Drug: Nalorex |
| Placebo | Placebo comparator | Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive volume-matched placebo Receives: Drug: Placebo; Drug: SL Buprenorphine; Drug: Nalorex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the time of maximum concentration (Tmax) of buprenorphine will be evaluated.
Measured: 84 days
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the maximum concentration (Cmax) of buprenorphine will be evaluated.
Measured: 84 days
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.
Measured: 84 days
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the half life of buprenorphine will be evaluated.
Measured: 84 days
Secondary outcomes (12)
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of Tmax of norbuprenorphine will be evaluated.
Measured: 84 days
Assessment of PK INDV-6200 (norbuprenorphine)
The key parameter of Cmax of norbuprenorphine will be evaluated.
Measured: 84 days
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of the half life of norbuprenorphine will be evaluated
Measured: 84 days
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.
Measured: 84 days
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)
Measured: Through day 84
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
Measured: Through day 84
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
Measured: Through day 84
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
Measured: Through day 84
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
Measured: Through day 84
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
Measured: Through day 84
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
Measured: Through day 84
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
Measured: Through day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2018
- Study start20 Sep 2017
- Primary completion7 Jun 2018
- Study completion7 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid-use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indivior Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nand Singh, Principal investigator, Quotient Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03715634
- Sponsor's protocol ID
- INDV-6200-101
- Status last verified
- Mar 2019
- First submitted
- 11 Oct 2018
- Last updated
- 4 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Novel Subcutaneous Depot Formulation of Buprenorphine (INDV-6200) in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03715634
- Acronym / sponsor ID
- INDV-6200-101
- Conditions
- Opioid-use Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Indivior Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Sep 2017 (actual)
- Primary completion
- 7 Jun 2018 (actual)
- Study completion
- 7 Jun 2018 (actual)
- First posted
- 23 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Depot buprenorphine (INDV-6200) | Experimental | Drug: INDV-6200, Drug: SL Buprenorphine, Drug: NalorexPeriod 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive depot buprenorphine |
| Placebo | Placebo comparator | Drug: Placebo, Drug: SL Buprenorphine, Drug: NalorexPeriod 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive volume-matched placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INDV-6200Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo | Drug | Depot buprenorphine (INDV-6200) |
| PlaceboSubjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo | Drug | Placebo |
| SL BuprenorphineAlso: SubutexAll subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability | Drug | Depot buprenorphine (INDV-6200), Placebo |
| NalorexBoth Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine | Drug | Depot buprenorphine (INDV-6200), Placebo |
Primary outcome
Assessment of PK of INDV-6200 (buprenorphine)
Time frame: 84 days
The key parameter of the time of maximum concentration (Tmax) of buprenorphine will be evaluated.
Assessment of PK of INDV-6200 (buprenorphine)
Time frame: 84 days
The key parameter of the maximum concentration (Cmax) of buprenorphine will be evaluated.
Assessment of PK of INDV-6200 (buprenorphine)
Time frame: 84 days
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)
Time frame: 84 days
The key parameter of the half life of buprenorphine will be evaluated.
12 secondary outcomes
Assessment of PK of INDV-6200 (norbuprenorphine)
Time frame: 84 days
Assessment of PK INDV-6200 (norbuprenorphine)
Time frame: 84 days
Assessment of PK of INDV-6200 (norbuprenorphine)
Time frame: 84 days
Assessment of PK of INDV-6200 (norbuprenorphine)
Time frame: 84 days
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in physical examination.
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in liver function tests.
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in systolic and diastolic blood pressure
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in heart rate
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by electrocardiogram (ECG) changes
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of erythema
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of swelling
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of pain
Time frame: Through day 84
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nand Singh principal investigator
Quotient Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INDV-6200, SL Buprenorphine and Nalorex in people with Opioid-use Disorder, run by Indivior Inc. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of PK of INDV-6200 (buprenorphine) (time frame: 84 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2019.