Opioid Use Disorder
Conditions
Keywords
medicine for opioid use disorder (MOUD)
Brief summary
Extended-release buprenorphine (SUBLOCADE®) injection is currently approved for subcutaneous administration in the abdomen for treatment of opioid use disorder (OUD). Having alternative injection sites is desirable to provide additional flexibility to patients, particularly for those who may prefer less visible or more convenient injection locations. The primary objective of this study is to assess the relative bioavailability of extended-release buprenorphine when administered at alternative injection locations (test treatments), in comparison to the abdomen (reference treatment).
Interventions
DRUGBuprenorphine Extended-Release Injection
Administered as a subcutaneous injection.
Sponsors
Indivior Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Signed the informed consent form (ICF) and have the ability to comply with the requirements and restrictions listed therein. 2. Sex: male or female. 3. Between the ages of 18 and 65 years inclusive, at the time of signing the ICF. 4. Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for moderate or severe opioid use disorder (OUD), or documented history of moderate to severe OUD and receiving/stabilized on medicine for opioid use disorder (MOUD). 5. Body mass index: ≥ 18.0 to ≤ 33.0 kg/m\^2. 6. New to treatment and seeking MOUD, or currently prescribed transmucosal (TM) buprenorphine (BUP) for OUD at the dose of 12 mg daily or can dose adjust to 12 mg daily. 7. Agree not to take any BUP-containing products, other than those administered for the current study, throughout the duration of the study.
Exclusion criteria
1. Has current diagnosis, other than OUD, requiring chronic opioid treatment. 2. Has concurrent primary substance use disorder, as defined by DSM-5 criteria, other than opioid, tobacco, cannabis, or mild to moderate alcohol use disorders. 3. Has target areas unsuitable for subcutaneous injections or evaluation of injections site (eg, nodules, scarring, lesions, excessive pigment) in the areas designated for possible injection in the study. 4. Has had significant traumatic injury or major surgical procedure (as defined by the investigator) within 30 days prior to the first dose of SUBLOCADE or still recovering from prior such injury or surgery. 5. Known personal and/or family history of congenital QT prolongation, or taking Class IA antiarrhythmic medications (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone) or other medications that prolong the QT interval. Known family history of sudden unexplained death. 6. Currently taking (within the 30 days prior to signing the ICF) prescription or over-the-counter medications that are clinically relevant CYP 3A4 or CYP 2C8 inducers or inhibitors (eg, rifampin, azole antifungals \[eg, ketoconazole\], macrolide antibiotics \[eg, erythromycin\]). 7. Has history of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent. 8. Has any active medical condition, or psychiatric illness, or social/legal situation (including court order requiring treatment for OUD), or organ disease, or concurrent medication/treatment that may compromise participant safety, interfere with study endpoints, or limit compliance with study requirements, or compromise the ability of the participant to provide written informed consent. 9. Moderate or severe hepatic impairment (Child-Pugh B or C). 10. Has known allergy or hypersensitivity to BUP or any component of the ATRIGEL Delivery System. 11. Concurrent or has had prior treatment with any BUP long-acting injectable product (eg, SUBLOCADE) in the past 3 years prior to consent; or treatment with depot naltrexone within the 3 months prior to consent. 12. Treatment with another investigational agent within 30 days prior to Screening or enrollment in another clinical study (except for an observational study). 13. Concurrent treatment with medications contraindicated for use with BUP as per local prescribing information. 14. Is a member of site staff, has a financial interest in Indivior, or is an immediate family member of anyone directly involved in the study (ie, site staff or Indivior employee).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration-time Curve From Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine | Day 1 at predose and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 hours post-dose and on Days 4, 6, 8, 11, 15, 18, 22, 25, and 29 |
| Maximum Observed Plasma Concentration (Cmax) of Buprenorphine | Day 1 at predose and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 hours post-dose and on Days 4, 6, 8, 11, 15, 18, 22, 25, and 29 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Serious Adverse Events | 28 days | — |
| Participants With Treatment-emergent Adverse Events | 28 days | — |
| Injection Site Pain | Day 1 at 1, 5, 10, 15, and 30 minutes post dosing | Measured on a 100 mm visual analog scale (VAS), where 0 represents no pain and 100 represents maximum pain. |
| Injection Site Grading | Day 1 at 10 minutes and 2 hours post dosing | Injection sites will be assessed for pain, tenderness, erythema/redness, induration, or swelling. Local injection site tolerability will be assigned a severity grade, including none (grade 0), mild (grade 1), moderate (grade 2), severe (grade 3), or potentially life-threatening (grade 4) utilizing the Injection Site Grading Scale. |
| Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | 28 days | — |
Countries
United States
Participant flow
Recruitment details
A total of 175 participants were screened to assess eligibility; of these, 132 received SUBOXONE during the Run-In Period (all eligible participants were attempted to be stabilized on 12 mg SUBOXONE \[buprenorphine/naloxone\] sublingual film once daily for a minimum of 7 days before the SUBLOCADE injection). 44 participants discontinued during the Run-In Period. A total of 88 participants were thus randomized (Started) to a treatment arm to receive extended-release buprenorphine on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Extended-release Buprenorphine: Abdomen Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the abdomen on Day 1.
Buprenorphine Extended-Release Injection: Administered as a subcutaneous injection. | 22 |
| Extended-release Buprenorphine: Upper Arm Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the back of the upper arm on Day 1.
Buprenorphine Extended-Release Injection: Administered as a subcutaneous injection. | 21 |
| Extended-release Buprenorphine: Buttocks Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the buttocks on Day 1.
Buprenorphine Extended-Release Injection: Administered as a subcutaneous injection. | 22 |
| Extended-release Buprenorphine: Thigh Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the thigh on Day 1.
Buprenorphine Extended-Release Injection: Administered as a subcutaneous injection. | 23 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Extended-release Buprenorphine: Abdomen | Extended-release Buprenorphine: Upper Arm | Extended-release Buprenorphine: Buttocks | Extended-release Buprenorphine: Thigh | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 10.35 | 43.9 years STANDARD_DEVIATION 9.61 | 45.6 years STANDARD_DEVIATION 8.94 | 36.7 years STANDARD_DEVIATION 7.89 | 41.2 years STANDARD_DEVIATION 9.77 |
| Body mass index | 26.87 kg/m^2 STANDARD_DEVIATION 4.698 | 25.95 kg/m^2 STANDARD_DEVIATION 5.011 | 26.06 kg/m^2 STANDARD_DEVIATION 4.259 | 26.30 kg/m^2 STANDARD_DEVIATION 4.5 | 26.30 kg/m^2 STANDARD_DEVIATION 4.552 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 17 Participants | 19 Participants | 18 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 6 Participants | 8 Participants | 4 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 14 Participants | 13 Participants | 18 Participants | 59 Participants |
| Region of Enrollment United States | 22 participants | 21 participants | 22 participants | 23 participants | 88 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 7 Participants | 11 Participants | 31 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 15 Participants | 12 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 132 | 0 / 22 | 0 / 21 | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 26 / 132 | 5 / 22 | 3 / 21 | 4 / 22 | 2 / 23 |
| serious Total, serious adverse events | 0 / 132 | 0 / 22 | 0 / 21 | 0 / 22 | 0 / 23 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine
Time frame: Day 1 at predose and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 hours post-dose and on Days 4, 6, 8, 11, 15, 18, 22, 25, and 29
Population: Pharmacokinetic Evaluable Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Extended-release Buprenorphine: Abdomen | Area Under the Plasma Concentration-time Curve From Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine | 1640 h*ng/mL | Geometric Coefficient of Variation 41.8 |
| Extended-release Buprenorphine: Upper Arm | Area Under the Plasma Concentration-time Curve From Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine | 1720 h*ng/mL | Geometric Coefficient of Variation 57.4 |
| Extended-release Buprenorphine: Buttocks | Area Under the Plasma Concentration-time Curve From Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine | 1570 h*ng/mL | Geometric Coefficient of Variation 42.7 |
| Extended-release Buprenorphine: Thigh | Area Under the Plasma Concentration-time Curve From Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine | 1870 h*ng/mL | Geometric Coefficient of Variation 56.2 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Buprenorphine
Time frame: Day 1 at predose and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 hours post-dose and on Days 4, 6, 8, 11, 15, 18, 22, 25, and 29
Population: Pharmacokinetic Evaluable Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Extended-release Buprenorphine: Abdomen | Maximum Observed Plasma Concentration (Cmax) of Buprenorphine | 6.61 ng/mL | Geometric Coefficient of Variation 46.9 |
| Extended-release Buprenorphine: Upper Arm | Maximum Observed Plasma Concentration (Cmax) of Buprenorphine | 9.17 ng/mL | Geometric Coefficient of Variation 85.8 |
| Extended-release Buprenorphine: Buttocks | Maximum Observed Plasma Concentration (Cmax) of Buprenorphine | 7.11 ng/mL | Geometric Coefficient of Variation 39.7 |
| Extended-release Buprenorphine: Thigh | Maximum Observed Plasma Concentration (Cmax) of Buprenorphine | 10.1 ng/mL | Geometric Coefficient of Variation 73.2 |
Secondary
Injection Site Grading
Injection sites will be assessed for pain, tenderness, erythema/redness, induration, or swelling. Local injection site tolerability will be assigned a severity grade, including none (grade 0), mild (grade 1), moderate (grade 2), severe (grade 3), or potentially life-threatening (grade 4) utilizing the Injection Site Grading Scale.
Time frame: Day 1 at 10 minutes and 2 hours post dosing
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Pain, None (Grade 0) at 10 minutes | 59.1 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Induration, Mild (Grade 1) at 2 hours | 13.6 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Erythema/redness, None (Grade 0) at 10 minutes | 86.4 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Tenderness, None (Grade 0) at 10 minutes | 59.1 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Tenderness, None (Grade 0) at 2 hours | 86.4 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Pain, Mild (Grade 1) at 10 minutes | 31.8 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 10 minutes | 13.6 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Injection site swelling, None (Grade 0) at 2 hours | 95.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 2 hours | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Induration, None (Grade 0) at 2 hours | 86.4 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Induration, None (Grade 0) at 10 minutes | 95.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Tenderness, Mild (Grade 1) at 10 minutes | 31.8 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Pain, Moderate (Grade 2) at 10 minutes | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Tenderness, Mild (Grade 1) at 2 hours | 13.6 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Induration, Mild (Grade 1) at 10 minutes | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Pain, Mild (Grade 1) at 2 hours | 0 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Pain, None (Grade 0) at 2 hours | 100.0 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 2 hours | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Injection site swelling, None (Grade 0) at 10 minutes | 90.9 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Tenderness, Moderate (Grade 2) at 10 minutes | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Erythema/redness, None (Grade 0) at 2 hours | 95.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 10 minutes | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Erythema/redness, None (Grade 0) at 2 hours | 90.5 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 10 minutes | 14.3 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Injection site swelling, None (Grade 0) at 2 hours | 85.7 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Tenderness, Mild (Grade 1) at 2 hours | 19.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Pain, None (Grade 0) at 2 hours | 81.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Pain, Mild (Grade 1) at 2 hours | 19.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Tenderness, None (Grade 0) at 10 minutes | 66.7 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Tenderness, None (Grade 0) at 2 hours | 81.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Tenderness, Mild (Grade 1) at 10 minutes | 33.3 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Pain, Mild (Grade 1) at 10 minutes | 28.6 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Induration, Mild (Grade 1) at 2 hours | 19.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Tenderness, Moderate (Grade 2) at 10 minutes | 0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Erythema/redness, None (Grade 0) at 10 minutes | 81.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Pain, None (Grade 0) at 10 minutes | 57.1 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Induration, None (Grade 0) at 2 hours | 81.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 10 minutes | 19.0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Induration, None (Grade 0) at 10 minutes | 85.7 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 2 hours | 9.5 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Induration, Mild (Grade 1) at 10 minutes | 14.3 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Pain, Moderate (Grade 2) at 10 minutes | 14.3 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Injection site swelling, None (Grade 0) at 10 minutes | 85.7 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 2 hours | 14.3 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Tenderness, Moderate (Grade 2) at 10 minutes | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Pain, None (Grade 0) at 10 minutes | 68.2 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Pain, Mild (Grade 1) at 10 minutes | 18.2 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Pain, Moderate (Grade 2) at 10 minutes | 13.6 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Tenderness, None (Grade 0) at 10 minutes | 77.3 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Tenderness, Mild (Grade 1) at 10 minutes | 22.7 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Erythema/redness, None (Grade 0) at 10 minutes | 86.4 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 10 minutes | 13.6 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Induration, None (Grade 0) at 10 minutes | 95.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Induration, Mild (Grade 1) at 10 minutes | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Injection site swelling, None (Grade 0) at 10 minutes | 90.9 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 10 minutes | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Pain, None (Grade 0) at 2 hours | 90.9 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Pain, Mild (Grade 1) at 2 hours | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Tenderness, None (Grade 0) at 2 hours | 95.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Tenderness, Mild (Grade 1) at 2 hours | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Erythema/redness, None (Grade 0) at 2 hours | 95.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 2 hours | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Induration, None (Grade 0) at 2 hours | 95.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Induration, Mild (Grade 1) at 2 hours | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Injection site swelling, None (Grade 0) at 2 hours | 90.9 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 2 hours | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Injection site swelling, None (Grade 0) at 10 minutes | 82.6 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Pain, Moderate (Grade 2) at 10 minutes | 8.7 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Erythema/redness, None (Grade 0) at 2 hours | 100.0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Induration, Mild (Grade 1) at 10 minutes | 13.0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Induration, None (Grade 0) at 10 minutes | 87.0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 2 hours | 13.0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 2 hours | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Erythema/redness, Mild (Grade 1) at 10 minutes | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Erythema/redness, None (Grade 0) at 10 minutes | 100.0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Pain, Mild (Grade 1) at 10 minutes | 34.8 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Induration, None (Grade 0) at 2 hours | 95.7 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Tenderness, Moderate (Grade 2) at 10 minutes | 4.3 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Tenderness, Mild (Grade 1) at 10 minutes | 39.1 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Pain, None (Grade 0) at 10 minutes | 56.5 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Pain, Mild (Grade 1) at 2 hours | 8.7 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Induration, Mild (Grade 1) at 2 hours | 4.3 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Tenderness, None (Grade 0) at 2 hours | 91.3 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Pain, None (Grade 0) at 2 hours | 91.3 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Injection site swelling, Mild (Grade 1) at 10 minutes | 17.4 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Tenderness, None (Grade 0) at 10 minutes | 56.5 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Tenderness, Mild (Grade 1) at 2 hours | 8.7 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Injection Site Grading | Injection site swelling, None (Grade 0) at 2 hours | 87.0 Percentage of participants |
Secondary
Injection Site Pain
Measured on a 100 mm visual analog scale (VAS), where 0 represents no pain and 100 represents maximum pain.
Time frame: Day 1 at 1, 5, 10, 15, and 30 minutes post dosing
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Extended-release Buprenorphine: Abdomen | Injection Site Pain | 15 minutes | 4.8 score on a scale | Standard Deviation 6.58 |
| Extended-release Buprenorphine: Abdomen | Injection Site Pain | 5 minutes | 23.2 score on a scale | Standard Deviation 26.13 |
| Extended-release Buprenorphine: Abdomen | Injection Site Pain | 30 minutes | 1.8 score on a scale | Standard Deviation 2.56 |
| Extended-release Buprenorphine: Abdomen | Injection Site Pain | 10 minutes | 12.0 score on a scale | Standard Deviation 14.88 |
| Extended-release Buprenorphine: Abdomen | Injection Site Pain | 1 minute | 37.5 score on a scale | Standard Deviation 27.95 |
| Extended-release Buprenorphine: Upper Arm | Injection Site Pain | 10 minutes | 9.4 score on a scale | Standard Deviation 11.8 |
| Extended-release Buprenorphine: Upper Arm | Injection Site Pain | 15 minutes | 6.0 score on a scale | Standard Deviation 8.76 |
| Extended-release Buprenorphine: Upper Arm | Injection Site Pain | 30 minutes | 4.5 score on a scale | Standard Deviation 8.69 |
| Extended-release Buprenorphine: Upper Arm | Injection Site Pain | 5 minutes | 16.0 score on a scale | Standard Deviation 16.59 |
| Extended-release Buprenorphine: Upper Arm | Injection Site Pain | 1 minute | 29.0 score on a scale | Standard Deviation 24.1 |
| Extended-release Buprenorphine: Buttocks | Injection Site Pain | 10 minutes | 8.2 score on a scale | Standard Deviation 14.15 |
| Extended-release Buprenorphine: Buttocks | Injection Site Pain | 1 minute | 27.4 score on a scale | Standard Deviation 32.02 |
| Extended-release Buprenorphine: Buttocks | Injection Site Pain | 5 minutes | 13.6 score on a scale | Standard Deviation 23.62 |
| Extended-release Buprenorphine: Buttocks | Injection Site Pain | 15 minutes | 4.9 score on a scale | Standard Deviation 11.8 |
| Extended-release Buprenorphine: Buttocks | Injection Site Pain | 30 minutes | 1.4 score on a scale | Standard Deviation 2.46 |
| Extended-release Buprenorphine: Thigh | Injection Site Pain | 15 minutes | 8.6 score on a scale | Standard Deviation 20.64 |
| Extended-release Buprenorphine: Thigh | Injection Site Pain | 5 minutes | 19.0 score on a scale | Standard Deviation 23.56 |
| Extended-release Buprenorphine: Thigh | Injection Site Pain | 1 minute | 29.3 score on a scale | Standard Deviation 28.99 |
| Extended-release Buprenorphine: Thigh | Injection Site Pain | 10 minutes | 12.5 score on a scale | Standard Deviation 21.3 |
| Extended-release Buprenorphine: Thigh | Injection Site Pain | 30 minutes | 6.6 score on a scale | Standard Deviation 19.93 |
Secondary
Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions
Time frame: 28 days
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Extended-release Buprenorphine: Abdomen | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site swelling | 0 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site induration | 0 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site reaction | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site pain | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site erythema | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site pain | 4.8 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site swelling | 4.8 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site reaction | 0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site induration | 4.8 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site erythema | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site pain | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site erythema | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site induration | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site swelling | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site reaction | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site swelling | 4.3 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site induration | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site erythema | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site pain | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Number of Participants With Treatment-emergent Adverse Events Identified as Injection Site Reactions | Injection site reaction | 0 Percentage of participants |
Secondary
Number of Participants With Treatment-emergent Serious Adverse Events
Time frame: 28 days
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Extended-release Buprenorphine: Abdomen | Number of Participants With Treatment-emergent Serious Adverse Events | 0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Number of Participants With Treatment-emergent Serious Adverse Events | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Number of Participants With Treatment-emergent Serious Adverse Events | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Number of Participants With Treatment-emergent Serious Adverse Events | 0 Percentage of participants |
Secondary
Participants With Treatment-emergent Adverse Events
Time frame: 28 days
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Extended-release Buprenorphine: Abdomen | Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 22.7 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Participants With Treatment-emergent Adverse Events | TEAE identified as injection site reaction | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Participants With Treatment-emergent Adverse Events | Related TEAE | 9.1 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Participants With Treatment-emergent Adverse Events | TEAE of opioid withdrawal symptom | 0 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Participants With Treatment-emergent Adverse Events | TEAE leading to death | 0 Percentage of participants |
| Extended-release Buprenorphine: Abdomen | Participants With Treatment-emergent Adverse Events | Severe TEAE | 0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Participants With Treatment-emergent Adverse Events | Severe TEAE | 0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Participants With Treatment-emergent Adverse Events | TEAE leading to death | 0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Participants With Treatment-emergent Adverse Events | TEAE of opioid withdrawal symptom | 0 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Participants With Treatment-emergent Adverse Events | Related TEAE | 4.8 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Participants With Treatment-emergent Adverse Events | TEAE identified as injection site reaction | 4.8 Percentage of participants |
| Extended-release Buprenorphine: Upper Arm | Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 14.3 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Participants With Treatment-emergent Adverse Events | TEAE leading to death | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Participants With Treatment-emergent Adverse Events | Related TEAE | 13.6 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Participants With Treatment-emergent Adverse Events | Severe TEAE | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Participants With Treatment-emergent Adverse Events | TEAE identified as injection site reaction | 4.5 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Participants With Treatment-emergent Adverse Events | TEAE of opioid withdrawal symptom | 0 Percentage of participants |
| Extended-release Buprenorphine: Buttocks | Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 18.2 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Participants With Treatment-emergent Adverse Events | TEAE of opioid withdrawal symptom | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Participants With Treatment-emergent Adverse Events | Related TEAE | 4.3 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Participants With Treatment-emergent Adverse Events | TEAE identified as injection site reaction | 4.3 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 8.7 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Participants With Treatment-emergent Adverse Events | Severe TEAE | 0 Percentage of participants |
| Extended-release Buprenorphine: Thigh | Participants With Treatment-emergent Adverse Events | TEAE leading to death | 0 Percentage of participants |