Opioid-Related Disorders
Conditions
Keywords
Opioid dependence
Brief summary
This study will evaluate the safety and tolerability on the oral mucosa of buprenorphine/naloxone film strips administered either sublingually or buccally daily for 12 weeks in opioid dependent individuals who are already on a stable regimen of buprenorphine/naloxone.
Detailed description
Buprenorphine and naloxone soluble film was developed as an alternative dosage form to Suboxone (buprenorphine and naloxone) sublingual tablets and was evaluated for both sublingual and buccal administration. The soluble film dosage is expected to provide the following enhancements and potential advantages over the current Suboxone (buprenorphine and naloxone) product: * mitigation against unintentional pediatric exposure by providing child-resistant packaging in unit dose format. * improvement in subject convenience and compliance by ensuring rapid disintegration. * protection against diversion by providing a dosage form that is very difficult for the subject to remove from the sublingual or buccal mucosa after administration. This provides assurance to the caregiver that the dose has actually been taken appropriately in a supervised setting. * provision of a unit dose product format for hospital and institutional use. * decreased product damage during shipping as compared to Suboxone tablets.
Interventions
Buprenorphine/naloxone dosed between 4/1 mg to 32/8 mg once a day for 12 weeks by sublingual route
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
Subjects must: * Be 18-to-65 years of age, inclusive. * Have a diagnosis of opioid dependence by medical history according to DSM-IV-TR criteria. * Be on stable dose of 4 to 32 mg (expressed as the buprenorphine component)daily of Suboxone for at least 30 days. * If female, have a negative pregnancy test during screening and agree to use an acceptable method of birth control which may include:
Exclusion criteria
Subjects must not: * Have participated in an experimental drug or device study within the last 30 days. * If female, be breast feeding or lactating. * Have any medical condition that in the opinion of the physician investigator would preclude the subject from completing the study. * Have a clinically significant abnormal finding (in the opinion of the Investigator) on oral cavity exam (e.g., active mouth ulcers). * Have any piercing of the tongue or mouth within 30 days prior to the first dose of study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-emergent Adverse Events Associated With the Oral Cavity. | 12 weeks | Safety and tolerability were evaluated during the 12-week Treatment Phase by oral cavity examination and assessment. Oral mucosa was graded as follows: Grade 0: Normal mucosa Grade 1: Localized mucosal erythema and/or irritation without ulceration Grade 2: Erythema and/or irritation and induration without ulceration Grade 3: Ulceration, with or without any other combination of signs |
| Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity | 12 weeks | Safety and tolerability were evaluated during the 12-week Treatment Phase by oral cavity examination and assessment. |
Countries
United States
Participant flow
Recruitment details
Patient enrollment commenced 02/28/08 and was completed 04/15/08. All sites were medical clinics.
Pre-assignment details
Subjects were required to be on a stabilized dose of buprenorphine and naloxone for at least 30 days prior to study drug administration, either during the screening period, or as part of routine medical treatment during the previous 30 days.
Participants by arm
| Arm | Count |
|---|---|
| Buprenorphine/Naloxone Film Strip Administered Sublingually | 194 |
| Buprenorphine/Naloxone Film Strip Administered Buccally | 188 |
| Total | 382 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Lost to Follow-up | 17 | 13 |
| Overall Study | Other Reason | 19 | 4 |
| Overall Study | Physician Decision | 10 | 14 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Sponsor's Decision | 11 | 7 |
| Overall Study | Withdrawal by Subject | 12 | 14 |
Baseline characteristics
| Characteristic | Buprenorphine/Naloxone Film Strip Administered Sublingually | Buprenorphine/Naloxone Film Strip Administered Buccally | Total |
|---|---|---|---|
| Age Categorical <21 | 4 Participants | 0 Participants | 4 Participants |
| Age Categorical 21 - 35 | 102 Participants | 99 Participants | 201 Participants |
| Age Categorical 36 - 50 | 71 Participants | 67 Participants | 138 Participants |
| Age Categorical >50 | 17 Participants | 22 Participants | 39 Participants |
| Age Continuous | 36.1 years STANDARD_DEVIATION 10.19 | 36.7 years STANDARD_DEVIATION 10.09 | 36.4 years STANDARD_DEVIATION 10.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 194 Participants | 188 Participants | 382 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 192 Participants | 187 Participants | 379 Participants |
| Region of Enrollment United States | 194 participants | 188 participants | 382 participants |
| Severity Grading of Oral Mucosa Grade 0 | 192 Participants | 185 Participants | 377 Participants |
| Severity Grading of Oral Mucosa Grade 1 | 2 Participants | 1 Participants | 3 Participants |
| Severity Grading of Oral Mucosa Grade 2 | 0 Participants | 1 Participants | 1 Participants |
| Severity Grading of Oral Mucosa Grade 3 | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 70 Participants | 72 Participants | 142 Participants |
| Sex: Female, Male Male | 124 Participants | 116 Participants | 240 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 194 | 16 / 188 |
| serious Total, serious adverse events | 4 / 194 | 2 / 188 |
Outcome results
Primary
Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity
Safety and tolerability were evaluated during the 12-week Treatment Phase by oral cavity examination and assessment.
Time frame: 12 weeks
Population: The population was defined as all subjects who received at least a single dose of study drug and was the only population considered in the analysis plan. Missing data values were not imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Buprenorphine/Naloxone Film Strip Administered Sublingually | Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity | Mild | 9 Participants |
| Buprenorphine/Naloxone Film Strip Administered Sublingually | Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity | Severe | 0 Participants |
| Buprenorphine/Naloxone Film Strip Administered Sublingually | Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity | Moderate | 2 Participants |
| Buprenorphine/Naloxone Film Strip Administered Buccally | Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity | Mild | 12 Participants |
| Buprenorphine/Naloxone Film Strip Administered Buccally | Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity | Moderate | 3 Participants |
| Buprenorphine/Naloxone Film Strip Administered Buccally | Number of Subjects With Mild, Moderate or Severe Treatment-emergent Adverse Events Associated With the Oral Cavity | Severe | 1 Participants |
Primary
Number of Subjects With Treatment-emergent Adverse Events Associated With the Oral Cavity.
Safety and tolerability were evaluated during the 12-week Treatment Phase by oral cavity examination and assessment. Oral mucosa was graded as follows: Grade 0: Normal mucosa Grade 1: Localized mucosal erythema and/or irritation without ulceration Grade 2: Erythema and/or irritation and induration without ulceration Grade 3: Ulceration, with or without any other combination of signs
Time frame: 12 weeks
Population: The population was defined as all subjects who received at least a single dose of study drug and was the only population considered in the analysis plan. Missing data values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Naloxone Film Strip Administered Sublingually | Number of Subjects With Treatment-emergent Adverse Events Associated With the Oral Cavity. | 11 Participants |
| Buprenorphine/Naloxone Film Strip Administered Buccally | Number of Subjects With Treatment-emergent Adverse Events Associated With the Oral Cavity. | 16 Participants |