Chronic Lower Back Pain, Chronic Pain
Conditions
Brief summary
This is a Phase III, placebo-controlled, multicenter study with an enriched-enrollment withdrawal (EEW) design to evaluate the efficacy and safety of CAM2038 in opioid-experienced subjects with moderate to severe CLBP that requires continuous, around-the-clock (ATC) opioid treatment ≥ 40 mg morphine equivalent dose (MED). The study includes 5 phases: A Screening Phase (up to 2 weeks), a Transition Phase (up to 2 weeks), an Open-Label Titration Phase (up to 10 weeks), a Double-Blind Treatment Phase including a Final Study Visit (12 weeks), and a Follow-up Phase (4 weeks). The overall duration of participation in the core phase of the study (randomized Double-Blind Phase) is up to 30 weeks, from the Screening Phase through the Follow-up Phase. Subjects who complete the Double-Blind Treatment Study Phase will be offered an opportunity to continue treatment in an open label safety extension for up to 60 weeks. Additional subjects may be recruited to open label safety extension to meet the goal of 100 subjects with 60 weeks of treatment.
Interventions
DRUGbuprenorphine
OTHERPlacebo
Sponsors
Medpace, Inc.
Camurus AB
Braeburn Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent provided prior to the conduct of any study-related procedures. 2. Male or non-pregnant, non-lactating female subject, greater than or equal to 18 years old. 3. Body mass index (BMI) between 18 and 38 kg/m2, inclusive. 4. Treated with daily opioids for moderate to severe CLBP for a minimum of 3 months prior to Screening. 5. On a stable dose of ≥40 mg/day of oral morphine or MED during the 14 days prior to Screening. 6. Systolic blood pressure ≥100 mmHg and diastolic blood pressure ≥60 mmHg. 7. Female subject of childbearing potential who is willing to use a reliable method of contraception during the entire study (Screening Visit to final Follow-up). To be considered not of childbearing potential, female subjects must be surgically sterile (hysterectomy or bilateral oophorectomy, or bilateral tubal ligation with surgery at least 6 weeks before Screening). 8. Male subject who is willing to use reliable contraception 9. Willing and able to comply with all study procedures and requirements.
Exclusion criteria
1. Positive for hepatitis B surface antigen, hepatitis C viral RNA, or antibodies to human immunodeficiency virus (HIV). 2. Clinically significant symptoms, medical conditions, or other circumstances which, in the opinion of the investigator, would preclude compliance with the protocol, adequate cooperation in the study, or obtaining informed consent, or may prevent the subject from safely participating in the study, including the following: 1. Severe respiratory insufficiency, respiratory depression, airway obstruction, gastrointestinal motility disorders, biliary tract disease, severe hepatic insufficiency, or planned surgery. 2. Bipolar disorder 3. Current diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-defined moderate to severe substance use disorder (including alcohol), other than caffeine or nicotine. 4. Female subject planning to become pregnant during the study. 5. Surgical procedure(s) for CLBP within 6 months prior to Screening. 6. Concomitant disease(s) that could prolong the QTcF interval, such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, Long QT Syndrome, or family history of Long QT Syndrome. 7. QTcF \>450 ms for males and \>470 ms for females, or clinically significant electrocardiogram (ECG) abnormality at Screening, at the investigator's discretion. 8. Currently taking medications that have the potential to prolong the QTcF interval or may require such medications during the course of the study (Appendix 1) and has clinically significant abnormalities on screening ECG readings, as determined by the investigator. 9. A nerve or plexus block, including epidural steroid injections or facet blocks, within 1 month prior to Screening or botulinum toxin injection in the lower back region within 3 months of Screening. 10. History of chemotherapy or confirmed malignancy (except basal cell carcinoma) within the past 2 years. 11. Any other acute or chronic pain condition that could interfere with the subject's ability to report their CLBP accurately and consistently and/or interfere with the study staff's ability to assess the subjects CLBP. 12. An active or pending workman's compensation, insurance claim, or litigation related to back pain (i.e., primary claim is back pain). 13. Clinically significant history, in the opinion of the investigator, of suicidal ideation or current evidence that the subject is actively suicidal. 14. Clinically significant history of major depressive disorder that is poorly controlled with medication, per investigator judgment. 15. Hypersensitivity or allergy to BPN, other opioids, or excipients of CAM2038. 16. Hypersensitivity or allergy to acetaminophen. 17. Use of strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4), such as some azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., clarithromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir) within the 30 days prior to Screening, 18. Use or planned use of natural supplements that can affect CYP3A4, such as St. John's Wort, throughout the study. 19. Has a major bleeding disorder, such as hemophilia, or treated with high levels of anticoagulants per the investigator's discretion. 20. Current or confirmed past diagnosis of Sphincter of Oddi dysfunction. 21. Has a significant hepatic disease, as indicated by Screening clinical laboratory assessment results (aspartate aminotransferase, alanine aminotransferase, or lactate dehydrogenase values ≥3 × the upper limit of normal \[ULN\]) or has a creatinine value ≥1.5 × ULN). 22. Is an employee of the investigator or the trial site, with direct involvement in the proposed trial or other studies under the direction of the investigator or trial site or is a family member of the investigator or of an employee of the investigator. 23. Has any pending legal action that could prohibit participation or compliance in the study. Criteria for Entry into the Titration Phase: 1. After at least a 12-hour washout from the last IR morphine dose, subject must have a COWS ≥5 and an API pain score over the past 24 hours ≥5 in order to receive a test dose of Buprenex. 2. Passed all baseline criteria, including a normal QTcF, had no change in QTcF \>30 ms at 1 hour after the test dose with Buprenex, and had a COWS score \<5 after the test dose with Buprenex. Note: * Subjects on BPN at Screening are required to participate in the down titration and will undergo a washout period prior to the test dose and first on-study treatment. Subjects entering the study on BPN will not transition to IR Morphine, but will refrain from taking their BPN for 12 -24 hours prior to the test dose to achieve the desired washout period. * Subjects on BPN at Screening are still required to follow the same Day 1 procedures (e.g., confirmation of pain scores, COWS assessment and Buprenex test dose) as non-BPN subjects. Criteria for Randomization into the Double-Blind Phase: 1. Been on a stable dose of CAM2038 q1w for at least 2 consecutive weeks. 2. CAM2038 titrated to a dose that provides analgesia (i.e., 7-day API score of ≤4 and at least 2 points below the value at the start of Titration Phase) and is well tolerated for 7 days before randomization. 3. Requires no more than an average of one hydrocodone/acetaminophen 5 mg/325 mg/day during the last 7 days prior to randomization. 4. Demonstrated study medication (CAM2038) compliance ≥80% during the previous 14 days. 5. Demonstrated daily compliance with pain intensity scoring for ≥11 of the previous 14 days, including the last 3 days prior to randomization. Inclusion Criteria for Open Label Extension For Subjects Continuing from The Randomized Double-Blind Phase. Subjects must have: 1. Completed Double Blind Phase of the study 2. Signed Informed Consent for Safety Extension Subjects completing the double-blind phase will be enrolled directly into the open label extension at their respective dose level of CAM2038. They will not be required to participate in a Buprenex treatment test dosing or participate in a titration phase. For De Novo Subjects (New Subjects Recruited Directly into The Open Label Extension) Subjects who are not participating in the Double-Blind Phase of the Study must meet all of the following inclusion criteria in order to be eligible for participation in the study: 1. Written informed consent provided prior to the conduct of any study-related procedures. 2. Male or non-pregnant and non-lactating female subject, greater than or equal to 18 years old. 3. BMI between 18 and 38 kg/m2, inclusive. 4. Treated with daily opioids for moderate to severe chronic pain disorder such as CLBP or osteoarthritis for a minimum of 3 months prior to Screening. 5. On a stable dose of \>40 mg/day of oral morphine or MED during the 14 days prior to Screening. 6. Systolic blood pressure ≥100 mmHg and diastolic blood pressure ≥60 mmHg. 7. Female subject of childbearing potential who is willing to use a reliable method of contraception during the entire study (Screening Visit to final Follow-up). To be considered not of childbearing potential, female subjects must be surgically sterile (hysterectomy or bilateral oophorectomy, or bilateral tubal ligation with surgery at least 6 weeks before Screening). 8. Male subject who is willing to use reliable contraception 9. Willing and able to comply with all study procedures and requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase. | 12 weeks- from randomization baseline to 12 weeks after randomization | Change from baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the primary timepoint will be Week 12 of the Double-Blind Phase based on the 11-Point numerical rating scale with 0 being no pain and 10 being the worst pain. |
| Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Change from baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase based on the 11-Point numerical rating scale with 10 being the worst pain. Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Rescue Medication Usage- Double-Blind Phase. | 12 weeks- from randomization baseline to 12 weeks after randomization | Rescue medication usage (number of days used) during the Double-Blind Phase. |
| Change From Open Label Titration Baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level Self-report Questionnaire Score. | 12 weeks- from randomization baseline to 12 weeks after randomization | Change from Open Label Titration baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level self-report questionnaire score. The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) descriptive system is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows subjects to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood, using a 5-level scale. These combinations of attributes were converted into a weighted health-state index score, according to the US population-based algorithm, with higher scores indicating better quality of life. The score ranges from 0-100 with 0 as the worst health and 100 as the best health. |
| Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | 23 weeks- from baseline to 12 weeks after randomization | Change from baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment score. The Work Productivity and Activity Impairment (WPAI) is a self-administered instrument used to measure the effect of general health and symptom severity on work productivity and regular activities, and yields 4 types of scores (higher scores indicate greater impairment): Absenteeism (work time missed)，Presenteeism (impairment at work/reduced on-the-job effectiveness), Work Productivity Loss (overall work impairment/absenteeism plus presenteeism)，and Activity Impairment. Scores range from 0-100 for each of the four types with higher scores indicating greater impairment. |
| Number of Subjects Discontinued Due to Loss of Efficacy | 12 weeks- from randomization baseline to 12 weeks after randomization | Number of Subjects Discontinued due to loss of efficacy, defined as discontinuation of study drug for lack of efficacy. |
| Change From Baseline to Week 12 of the Double-Blind Phase in Patient Global Impression of Improvement (PGI-I) Scale | 12 weeks- from baseline (randomization) to 12 weeks after randomization | Change from baseline to Week 12 of the Double-Blind Phase in Patient global Impression of Improvement (PGI-I) Scale. PGI-I)Scale is a single question 7-point likert scale that required the subject to assess how much his/her pain had improved or worsened relative to the start of the study at the beginning of the intervention . Ratings were: 1, much worse; 2, worse; 3, a little worse; 4, no change; 5, a little better; 6, better; or 7, much better |
| Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Change from baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) and the primary timepoint will be Week 52 of the Open Label Phase based on the 11-Point numerical rating scale with 10 being the worst pain. Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects. |
| Change From Baseline in the Weekly Average of (Daily) Worst Pain Intensity Scores at Week 12 of the Double-Blind Phase Based on 11-Point Numerical Rating Scale With 10 Being the Worst Pain. | 12 weeks- from randomization baseline to 12 weeks after randomization | Change from baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) and the primary timepoint will be Week 12 of the Double-Blind Phase based on the 11-Point numerical rating scale with 0 being no pain and 10 being the worst pain. |
| Summary of Rescue Medication Usage-Open Label Phase | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Rescue medication usage (number of days used) during the Open Label Phase. |
| Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Change from Open Label Titration baseline in EuroQol Group 5-dimension 5-level self-report questionnaire score in the Open Label Phase. The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) descriptive system is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows subjects to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood, using a 5-level scale. These combinations of attributes were converted into a weighted health-state index score, according to the US population-based algorithm, with higher scores indicating better quality of life. The score ranges from 0-100 with 0 as the worst health and 100 as the best health. |
| Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Summary of Change from Baseline in Clinical Global Impression of Improvement (CGI-I) scale. The Clinician Global Impression of Improvement (CGI-I) Scale is a 7-point scale that required the clinician to assess how much the subject's Pain had improved or worsened relative to the start of the study. Assessments were rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse |
| Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Change from baseline in the Open Label Phase in Patient global Impression of Improvement (PGI-I) Scale. PGI-I Scale is a single question 7-point likert scale that required the subject to assess how much his/her pain had improved or worsened relative to the start of the study. Ratings were: 1, much worse; 2, worse; 3, a little worse; 4, no change; 5, a little better; 6, better; or 7, much better |
| Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Change from baseline in the Open Label Phase in Work Productivity and Activity Impairment score with a range of 0-100 for 4 types of scores with higher scores indicating greater impairment. The Work Productivity and Activity Impairment (WPAI) is a self-administered instrument used to measure the effect of general health and symptom severity on work productivity and regular activities, and yields 4 types of scores (higher scores indicate greater impairment): Absenteeism (work time missed)，Presenteeism (impairment at work/reduced on-the-job effectiveness), Work Productivity Loss (overall work impairment/absenteeism plus presenteeism)，and Activity Impairment. Scores range from 0-100 for each of the four types with higher scores indicating greater impairment. |
| Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy. | 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects). | Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy Open Label Phase. |
| Number of Subjects With a 30% and 50% Reduction in WAAPI From Baseline to Week 12 of the Double-Blind Phase. | 12 weeks- from randomization baseline to 12 weeks after randomization | Number of Responders With a 30% and 50% Reduction in WAAPI from the Open-Label Titration Period Baseline to Week 12 of the Double-Blind Treatment Period (mITT Population) |
Countries
United States
Participant flow
Recruitment details
965 of those subjects entered the Double Blind phase of the study. 108 subjects signed consent as De Novo subjects, but 20 of those subjects were part of the Double Blind phase. The total number of subjects that signed consent was 1053 (965 + 88).Two sites had quality issues with the data, so those subjects were eliminated from the analysis. This made the total number of subjects who were analyzed 222 in the double blind randomized phase and 132 subjects for the open label phase.
Pre-assignment details
Subjects are screened prior to entry into a titration phase where they are titrated to an appropriate dose. Once they are titrated, they were randomized and entered the double blind period or open label period for de novo subjects.
Participants by arm
| Arm | Count |
|---|---|
| CAM2038 q1w or q4w BPN Treatment- Double Blind Phase CAM2038 50 mg/mL q1w at doses of 8 mg, 12 mg, 16 mg, 24 mg, or 32 mg. CAM2038 356 mg/mL q4w at doses of 64 mg, 96 mg, or 128 mg. buprenorphine | 112 |
| Placebo Subcutaneous Injections-Double Blind Phase CAM2038 placebo: 0.16, 0.18, 0.24, 0.27, 0.36, and 0.64 mL SC injection administered once weekly or once monthly (matching volumes for CAM2038 q1w and near-matching volumes for CAM2038 q4w). | 110 |
| De Novo Subjects-Open Label CAM2038 q1w (buprenorphine FluidCrystal®) : SC injection depot for once weekly or monthly administration at doses of 4, 8, 12, 16, 24 and 32 mg (buprenorphine base) 0.16, 0.24, and 0.64 mL SC injection CAM2038 (buprenorphine FluidCrystal® once-weekly injection depot)
CAM2038 q4w ( buprenorphine FluidCrystal®): SC injection depot for once monthly administration (356 mg/mL) at doses of 64, 96, 128 or 160 mg (buprenorphine base) 0.18, 0.27, and 0.36 mL SC injection CAM2038 (buprenorphine FluidCrystal® once-monthly injection depot) | 75 |
| Rollover Subjects-Open Label CAM2038 q1w (buprenorphine FluidCrystal®) : SC injection depot for once weekly or monthly administration at doses of 4, 8, 12, 16, 24 and 32 mg (buprenorphine base) 0.16, 0.24, and 0.64 mL SC injection CAM2038 (buprenorphine FluidCrystal® once-weekly injection depot)
CAM2038 q4w ( buprenorphine FluidCrystal®): SC injection depot for once monthly administration (356 mg/mL) at doses of 64, 96, 128 or 160 mg (buprenorphine base) 0.18, 0.27, and 0.36 mL SC injection CAM2038 (buprenorphine FluidCrystal® once-monthly injection depot) | 57 |
| Total | 354 |
Baseline characteristics
| Characteristic | CAM2038 q1w or q4w BPN Treatment- Double Blind Phase | Total | Placebo Subcutaneous Injections-Double Blind Phase | De Novo Subjects-Open Label | Rollover Subjects-Open Label |
|---|---|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 12.19 | 55.2 years STANDARD_DEVIATION 10.82 | 54.7 years STANDARD_DEVIATION 11.36 | 54.3 years STANDARD_DEVIATION 10.27 | 56.4 years STANDARD_DEVIATION 11.49 |
| Body Mass Index | 29.1 kg/m^2 STANDARD_DEVIATION 4.78 | 29.2 kg/m^2 STANDARD_DEVIATION 5.02 | 29.3 kg/m^2 STANDARD_DEVIATION 5.27 | 29.5 kg/m^2 STANDARD_DEVIATION 5.55 | 29.1 kg/m^2 STANDARD_DEVIATION 5.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 22 Participants | 11 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 101 Participants | 198 Participants | 97 Participants | 73 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants |
| Pain Score at Start of Open-Label Titration Period | 7.0 units on a scale STANDARD_DEVIATION 1.42 | 7.0 units on a scale STANDARD_DEVIATION 1.4 | 7.0 units on a scale STANDARD_DEVIATION 1.39 | 6.7 units on a scale STANDARD_DEVIATION 1.46 | 6.6 units on a scale STANDARD_DEVIATION 1.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 22 Participants | 12 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 100 Participants | 116 Participants | 97 Participants | 67 Participants | 49 Participants |
| Sex: Female, Male Female | 66 Participants | 78 Participants | 56 Participants | 44 Participants | 34 Participants |
| Sex: Female, Male Male | 46 Participants | 54 Participants | 54 Participants | 31 Participants | 23 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 468 | 0 / 112 | 1 / 110 | 0 / 75 | 0 / 46 | 0 / 54 | 0 / 55 |
| other Total, other adverse events | 300 / 468 | 36 / 112 | 32 / 110 | 41 / 75 | 15 / 46 | 41 / 54 | 46 / 55 |
| serious Total, serious adverse events | 10 / 468 | 3 / 112 | 3 / 110 | 1 / 75 | 1 / 46 | 7 / 54 | 7 / 55 |
Outcome results
Primary
Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase.
Change from baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the primary timepoint will be Week 12 of the Double-Blind Phase based on the 11-Point numerical rating scale with 0 being no pain and 10 being the worst pain.
Time frame: 12 weeks- from randomization baseline to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase. | Baseline | 2.7 score on a scale | Standard Deviation 1.26 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase. | Change from Baseline to Week 12 | -0.9 score on a scale | Standard Deviation 1.62 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase. | Baseline | 2.4 score on a scale | Standard Deviation 1.25 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) and the Primary Timepoint Will be Week 12 of the Double-Blind Phase. | Change from Baseline to Week 12 | -1.9 score on a scale | Standard Deviation 1.97 |
Primary
Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase.
Change from baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase based on the 11-Point numerical rating scale with 10 being the worst pain. Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects.
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 44 | -0.767 score on a scale | Standard Deviation 1.32 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 32 | -0.941 score on a scale | Standard Deviation 1.64 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 20 | -0.690 score on a scale | Standard Deviation 1.47 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 8 | -0.555 score on a scale | Standard Deviation 1.28 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 28 | -0.905 score on a scale | Standard Deviation 1.56 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 24 | -0.718 score on a scale | Standard Deviation 1.46 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Baseline | 2.839 score on a scale | Standard Deviation 1.0753 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 4 | -0.434 score on a scale | Standard Deviation 0.94 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 40 | -0.913 score on a scale | Standard Deviation 1.37 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 12 | -0.752 score on a scale | Standard Deviation 1.35 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 48 | -0.996 score on a scale | Standard Deviation 1.39 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 36 | -0.920 score on a scale | Standard Deviation 1.48 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 16 | -0.543 score on a scale | Standard Deviation 1.19 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 24 | -0.872 score on a scale | Standard Deviation 1.51 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Baseline | 2.256 score on a scale | Standard Deviation 1.1642 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 4 | -0.531 score on a scale | Standard Deviation 0.93 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 8 | -0.729 score on a scale | Standard Deviation 0.99 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 12 | -0.767 score on a scale | Standard Deviation 1.2 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 16 | -0.312 score on a scale | Standard Deviation 0.68 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 20 | -0.566 score on a scale | Standard Deviation 1.05 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 28 | -0.338 score on a scale | Standard Deviation 1.06 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 32 | -0.275 score on a scale | Standard Deviation 1.41 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 36 | -0.623 score on a scale | Standard Deviation 1.36 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 40 | -0.519 score on a scale | Standard Deviation 1.51 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 44 | -0.560 score on a scale | Standard Deviation 1.37 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 48 | -0.619 score on a scale | Standard Deviation 1.58 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 32 | -1.111 score on a scale | Standard Deviation 1.27 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 12 | -2.079 score on a scale | Standard Deviation 2.01 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 44 | -1.282 score on a scale | Standard Deviation 1.57 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 36 | -1.119 score on a scale | Standard Deviation 1.42 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 8 | -2.165 score on a scale | Standard Deviation 2.2 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Baseline | 1.944 score on a scale | Standard Deviation 1.1288 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 40 | -1.113 score on a scale | Standard Deviation 1.49 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 24 | -1.220 score on a scale | Standard Deviation 1.41 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 20 | -1.013 score on a scale | Standard Deviation 1.63 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 4 | -1.586 score on a scale | Standard Deviation 1.8 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 28 | -1.212 score on a scale | Standard Deviation 1.46 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 16 | -1.229 score on a scale | Standard Deviation 1.42 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Average Pain Intensity (WAAPI) of the Open Label Phase. | Change from Baseline to Week 48 | -1.215 score on a scale | Standard Deviation 1.57 |
Secondary
Change From Baseline in the Weekly Average of (Daily) Worst Pain Intensity Scores at Week 12 of the Double-Blind Phase Based on 11-Point Numerical Rating Scale With 10 Being the Worst Pain.
Change from baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) and the primary timepoint will be Week 12 of the Double-Blind Phase based on the 11-Point numerical rating scale with 0 being no pain and 10 being the worst pain.
Time frame: 12 weeks- from randomization baseline to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in the Weekly Average of (Daily) Worst Pain Intensity Scores at Week 12 of the Double-Blind Phase Based on 11-Point Numerical Rating Scale With 10 Being the Worst Pain. | Baseline | 3.8 score on a scale | Standard Deviation 1.59 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in the Weekly Average of (Daily) Worst Pain Intensity Scores at Week 12 of the Double-Blind Phase Based on 11-Point Numerical Rating Scale With 10 Being the Worst Pain. | Change from Baseline to Week 12 | -1.1 score on a scale | Standard Deviation 1.81 |
| Placebo Subcutaneous Injections | Change From Baseline in the Weekly Average of (Daily) Worst Pain Intensity Scores at Week 12 of the Double-Blind Phase Based on 11-Point Numerical Rating Scale With 10 Being the Worst Pain. | Baseline | 3.7 score on a scale | Standard Deviation 1.65 |
| Placebo Subcutaneous Injections | Change From Baseline in the Weekly Average of (Daily) Worst Pain Intensity Scores at Week 12 of the Double-Blind Phase Based on 11-Point Numerical Rating Scale With 10 Being the Worst Pain. | Change from Baseline to Week 12 | -2.2 score on a scale | Standard Deviation 2.18 |
Secondary
Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase.
Change from baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) and the primary timepoint will be Week 52 of the Open Label Phase based on the 11-Point numerical rating scale with 10 being the worst pain. Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects.
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 44 | -0.897 score on a scale | Standard Deviation 1.56 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 32 | -0.996 score on a scale | Standard Deviation 1.9 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 20 | -0.725 score on a scale | Standard Deviation 1.59 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 8 | -0.625 score on a scale | Standard Deviation 1.48 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 28 | -1.013 score on a scale | Standard Deviation 1.55 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 24 | -0.735 score on a scale | Standard Deviation 1.67 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Baseline | 4.139 score on a scale | Standard Deviation 1.55 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 4 | -0.517 score on a scale | Standard Deviation 1.34 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 40 | -0.935 score on a scale | Standard Deviation 1.5 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 12 | -0.846 score on a scale | Standard Deviation 1.53 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 48 | -1.059 score on a scale | Standard Deviation 1.59 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 36 | -1.044 score on a scale | Standard Deviation 1.71 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 16 | -0.689 score on a scale | Standard Deviation 1.51 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 24 | -0.902 score on a scale | Standard Deviation 2.13 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Baseline | 3.717 score on a scale | Standard Deviation 3.86 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 4 | -0.859 score on a scale | Standard Deviation 1.57 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 8 | -1.066 score on a scale | Standard Deviation 1.68 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 12 | -1.157 score on a scale | Standard Deviation 1.95 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 16 | -0.487 score on a scale | Standard Deviation 1.14 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 20 | -0.592 score on a scale | Standard Deviation 1.157 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 28 | -0.518 score on a scale | Standard Deviation 1.74 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 32 | -0.322 score on a scale | Standard Deviation 1.76 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 36 | -0.682 score on a scale | Standard Deviation 0.2 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 40 | -0.658 score on a scale | Standard Deviation 1.92 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 44 | -0.764 score on a scale | Standard Deviation 2.03 |
| Placebo Subcutaneous Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 48 | -0.896 score on a scale | Standard Deviation 2.26 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 32 | -1.462 score on a scale | Standard Deviation 2.06 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 12 | -2.455 score on a scale | Standard Deviation 2.26 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 44 | -1.216 score on a scale | Standard Deviation 1.68 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 36 | -1.112 score on a scale | Standard Deviation 1.34 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 8 | -2.404 score on a scale | Standard Deviation 2.47 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Baseline | 3.246 score on a scale | Standard Deviation 3.29 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 40 | -1.087 score on a scale | Standard Deviation 1.48 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 24 | -1.461 score on a scale | Standard Deviation 1.97 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 20 | -1.391 score on a scale | Standard Deviation 2.18 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 4 | -1.734 score on a scale | Standard Deviation 1.97 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 28 | -1.531 score on a scale | Standard Deviation 2.13 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 16 | -1.587 score on a scale | Standard Deviation 2.03 |
| Rollover Placebo Injections | Change From Baseline in Weekly Average of (Daily) Worst Pain Intensity (WAWPI) of the Open Label Phase. | Change from Baseline to Week 48 | -1.292 score on a scale | Standard Deviation 1.78 |
Secondary
Change From Baseline to Week 12 of the Double-Blind Phase in Patient Global Impression of Improvement (PGI-I) Scale
Change from baseline to Week 12 of the Double-Blind Phase in Patient global Impression of Improvement (PGI-I) Scale. PGI-I)Scale is a single question 7-point likert scale that required the subject to assess how much his/her pain had improved or worsened relative to the start of the study at the beginning of the intervention . Ratings were: 1, much worse; 2, worse; 3, a little worse; 4, no change; 5, a little better; 6, better; or 7, much better
Time frame: 12 weeks- from baseline (randomization) to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Patient Global Impression of Improvement (PGI-I) Scale | Baseline | 6.0 units on a scale | Standard Deviation 0.96 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Patient Global Impression of Improvement (PGI-I) Scale | Change from Baseline to Week 12 | 0.4 units on a scale | Standard Deviation 1.48 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Patient Global Impression of Improvement (PGI-I) Scale | Baseline | 6.2 units on a scale | Standard Deviation 0.74 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Patient Global Impression of Improvement (PGI-I) Scale | Change from Baseline to Week 12 | 1.5 units on a scale | Standard Deviation 1.63 |
Secondary
Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score
Change from baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment score. The Work Productivity and Activity Impairment (WPAI) is a self-administered instrument used to measure the effect of general health and symptom severity on work productivity and regular activities, and yields 4 types of scores (higher scores indicate greater impairment): Absenteeism (work time missed)，Presenteeism (impairment at work/reduced on-the-job effectiveness), Work Productivity Loss (overall work impairment/absenteeism plus presenteeism)，and Activity Impairment. Scores range from 0-100 for each of the four types with higher scores indicating greater impairment.
Time frame: 23 weeks- from baseline to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Activity Impairment | 58.8 score on a scale | Standard Deviation 23.68 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization-Activity impairment | 18.1 score on a scale | Standard Deviation 24.88 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Absenteesim | 5.1 score on a scale | Standard Deviation 10.19 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization-Absenteesim | -0.8 score on a scale | Standard Deviation 10.75 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Presenteeism | 38.9 score on a scale | Standard Deviation 22.33 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization-Presenteeism | 5.0 score on a scale | Standard Deviation 27.47 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Work Productivity Loss | 41.3 score on a scale | Standard Deviation 23.09 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization- Work Productivity Loss | 5.4 score on a scale | Standard Deviation 23.05 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization- Work Productivity Loss | 7.8 score on a scale | Standard Deviation 26.4 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Activity Impairment | 61.2 score on a scale | Standard Deviation 22.74 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Presenteeism | 47.8 score on a scale | Standard Deviation 25.2 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization-Activity impairment | 11.7 score on a scale | Standard Deviation 26.28 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Work Productivity Loss | 52.3 score on a scale | Standard Deviation 26.77 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Baseline-Absenteesim | 9.9 score on a scale | Standard Deviation 22.5 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization-Presenteeism | 9.0 score on a scale | Standard Deviation 27.37 |
| Placebo Subcutaneous Injections | Change From Baseline to Week 12 of the Double-Blind Phase in Work Productivity and Activity Impairment Score | Change from Baseline to Week 12 after randomization-Absenteesim | -4.6 score on a scale | Standard Deviation 22.88 |
Secondary
Change From Open Label Titration Baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level Self-report Questionnaire Score.
Change from Open Label Titration baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level self-report questionnaire score. The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) descriptive system is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows subjects to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood, using a 5-level scale. These combinations of attributes were converted into a weighted health-state index score, according to the US population-based algorithm, with higher scores indicating better quality of life. The score ranges from 0-100 with 0 as the worst health and 100 as the best health.
Time frame: 12 weeks- from randomization baseline to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Open Label Titration Baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level Self-report Questionnaire Score. | Titration Baseline | 63.7 units on a scale | Standard Deviation 20.55 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Change From Open Label Titration Baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level Self-report Questionnaire Score. | Change from Baseline to Week 12 | -9.4 units on a scale | Standard Deviation 18.47 |
| Placebo Subcutaneous Injections | Change From Open Label Titration Baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level Self-report Questionnaire Score. | Titration Baseline | 61.3 units on a scale | Standard Deviation 22.05 |
| Placebo Subcutaneous Injections | Change From Open Label Titration Baseline to Week 12 of the Double-Blind Phase in EuroQol Group 5-dimension 5-level Self-report Questionnaire Score. | Change from Baseline to Week 12 | -7.2 units on a scale | Standard Deviation 23.04 |
Secondary
Number of Subjects Discontinued Due to Loss of Efficacy
Number of Subjects Discontinued due to loss of efficacy, defined as discontinuation of study drug for lack of efficacy.
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Number of Subjects Discontinued Due to Loss of Efficacy | 1 Participants |
| Placebo Subcutaneous Injections | Number of Subjects Discontinued Due to Loss of Efficacy | 0 Participants |
| Rollover Placebo Injections | Number of Subjects Discontinued Due to Loss of Efficacy | 1 Participants |
Secondary
Number of Subjects Discontinued Due to Loss of Efficacy
Number of Subjects Discontinued due to loss of efficacy, defined as discontinuation of study drug for lack of efficacy.
Time frame: 12 weeks- from randomization baseline to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Number of Subjects Discontinued Due to Loss of Efficacy | 7 Participants |
| Placebo Subcutaneous Injections | Number of Subjects Discontinued Due to Loss of Efficacy | 21 Participants |
Secondary
Number of Subjects With a 30% and 50% Reduction in WAAPI From Baseline to Week 12 of the Double-Blind Phase.
Number of Responders With a 30% and 50% Reduction in WAAPI from the Open-Label Titration Period Baseline to Week 12 of the Double-Blind Treatment Period (mITT Population)
Time frame: 12 weeks- from randomization baseline to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Number of Subjects With a 30% and 50% Reduction in WAAPI From Baseline to Week 12 of the Double-Blind Phase. | >= 30% improvement | 60 Participants |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Number of Subjects With a 30% and 50% Reduction in WAAPI From Baseline to Week 12 of the Double-Blind Phase. | >= 50% improvement | 44 Participants |
| Placebo Subcutaneous Injections | Number of Subjects With a 30% and 50% Reduction in WAAPI From Baseline to Week 12 of the Double-Blind Phase. | >= 30% improvement | 47 Participants |
| Placebo Subcutaneous Injections | Number of Subjects With a 30% and 50% Reduction in WAAPI From Baseline to Week 12 of the Double-Blind Phase. | >= 50% improvement | 32 Participants |
Secondary
Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy.
Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy Open Label Phase.
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy. | 1 Participants |
| Placebo Subcutaneous Injections | Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy. | 0 Participants |
| Rollover Placebo Injections | Subject Discontinued Due to Loss of Efficacy, Defined as Discontinuation of Study Drug for Lack of Efficacy. | 1 Participants |
Secondary
Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label
Summary of Change from Baseline in Clinical Global Impression of Improvement (CGI-I) scale. The Clinician Global Impression of Improvement (CGI-I) Scale is a 7-point scale that required the clinician to assess how much the subject's Pain had improved or worsened relative to the start of the study. Assessments were rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label | Baseline | 1.9 score on a scale | Standard Deviation 0.79 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label | Change from Baseline at End of Treatment Visit | -0.4 score on a scale | Standard Deviation 1.25 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label | Baseline | 1.7 score on a scale | Standard Deviation 0.56 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label | Change from Baseline at End of Treatment Visit | -0.1 score on a scale | Standard Deviation 1.08 |
| Rollover Placebo Injections | Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label | Baseline | 2.0 score on a scale | Standard Deviation 1.13 |
| Rollover Placebo Injections | Summary of Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Scale-Open Label | Change from Baseline at End of Treatment Visit | 0.1 score on a scale | Standard Deviation 1.31 |
Secondary
Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase
Change from Open Label Titration baseline in EuroQol Group 5-dimension 5-level self-report questionnaire score in the Open Label Phase. The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) descriptive system is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows subjects to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood, using a 5-level scale. These combinations of attributes were converted into a weighted health-state index score, according to the US population-based algorithm, with higher scores indicating better quality of life. The score ranges from 0-100 with 0 as the worst health and 100 as the best health.
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase | Baseline | 76.59 score on a scale | Standard Deviation 13.31 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase | Change from Baseline at End of Treatment Visit | 5.17 score on a scale | Standard Deviation 15.43 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase | Baseline | 83.38 score on a scale | Standard Deviation 14.89 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase | Change from Baseline at End of Treatment Visit | 9.95 score on a scale | Standard Deviation 18.83 |
| Rollover Placebo Injections | Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase | Baseline | 79.65 score on a scale | Standard Deviation 14 |
| Rollover Placebo Injections | Summary of Change From Baseline in EuroQoL Group EQ-5D-5L Scores Over Time-Open Label Phase | Change from Baseline at End of Treatment Visit | 6.35 score on a scale | Standard Deviation 18.95 |
Secondary
Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale
Change from baseline in the Open Label Phase in Patient global Impression of Improvement (PGI-I) Scale. PGI-I Scale is a single question 7-point likert scale that required the subject to assess how much his/her pain had improved or worsened relative to the start of the study. Ratings were: 1, much worse; 2, worse; 3, a little worse; 4, no change; 5, a little better; 6, better; or 7, much better
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale | Baseline | 5.8 score on a scale | Standard Deviation 0.84 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale | Change from Baseline at End of Treatment Visit | 0.2 score on a scale | Standard Deviation 1.16 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale | Baseline | 6.1 score on a scale | Standard Deviation 1.1 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale | Change from Baseline at End of Treatment Visit | -0.2 score on a scale | Standard Deviation 1.04 |
| Rollover Placebo Injections | Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale | Baseline | 6.3 score on a scale | Standard Deviation 0.84 |
| Rollover Placebo Injections | Summary of Change From Baseline in Patient Global Impression of Improvement (PGI-I) Scale | Change from Baseline at End of Treatment Visit | 0.5 score on a scale | Standard Deviation 0.92 |
Secondary
Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase
Change from baseline in the Open Label Phase in Work Productivity and Activity Impairment score with a range of 0-100 for 4 types of scores with higher scores indicating greater impairment. The Work Productivity and Activity Impairment (WPAI) is a self-administered instrument used to measure the effect of general health and symptom severity on work productivity and regular activities, and yields 4 types of scores (higher scores indicate greater impairment): Absenteeism (work time missed)，Presenteeism (impairment at work/reduced on-the-job effectiveness), Work Productivity Loss (overall work impairment/absenteeism plus presenteeism)，and Activity Impairment. Scores range from 0-100 for each of the four types with higher scores indicating greater impairment.
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Absenteesim | 1.538 score on a scale | Standard Deviation 5.55 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Absenteesim | 0 score on a scale | Standard Deviation 0 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Presenteeism | 26.9 score on a scale | Standard Deviation 18.43 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Presenteeism | 1.0 score on a scale | Standard Deviation 15.95 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Work Productivity Loss | 27.846 score on a scale | Standard Deviation 19.42 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit- Work Productivity Loss | 1.000 score on a scale | Standard Deviation 15.95 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Activity Impairment | 32.1 score on a scale | Standard Deviation 20.55 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Activity Impairment | -12.1 score on a scale | Standard Deviation 22.2 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Presenteeism | 22.9 score on a scale | Standard Deviation 19.76 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Activity Impairment | 29.0 score on a scale | Standard Deviation 23.82 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Presenteeism | 1.7 score on a scale | Standard Deviation 7.53 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Work Productivity Loss | 22.857 score on a scale | Standard Deviation 19.76 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit- Work Productivity Loss | -0.043 score on a scale | Standard Deviation 11.05 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Absenteesim | 0 score on a scale | Standard Deviation 0 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Absenteesim | -2.137 score on a scale | Standard Deviation 5.23 |
| Placebo Subcutaneous Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Activity Impairment | -6.5 score on a scale | Standard Deviation 25.6 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Presenteeism | 21.0 score on a scale | Standard Deviation 11.97 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Absenteesim | 0 score on a scale | Standard Deviation 0 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Absenteesim | 0 score on a scale | Standard Deviation 0 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Presenteeism | 6.7 score on a scale | Standard Deviation 23.98 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Activity Impairment | 22.9 score on a scale | Standard Deviation 16.52 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit- Work Productivity Loss | 6.667 score on a scale | Standard Deviation 23.98 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Baseline-Work Productivity Loss | 21.000 score on a scale | Standard Deviation 11.97 |
| Rollover Placebo Injections | Summary of Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Open Label Phase | Change from Baseline at End of Treatment Visit-Activity Impairment | -18.2 score on a scale | Standard Deviation 22.45 |
Secondary
Summary of Rescue Medication Usage- Double-Blind Phase.
Rescue medication usage (number of days used) during the Double-Blind Phase.
Time frame: 12 weeks- from randomization baseline to 12 weeks after randomization
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage- Double-Blind Phase. | Baseline | 3.4 Days | Standard Deviation 2.84 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage- Double-Blind Phase. | Change from Baseline to Week 12 | -1.5 Days | Standard Deviation 2.58 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage- Double-Blind Phase. | Baseline | 3.5 Days | Standard Deviation 2.91 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage- Double-Blind Phase. | Change from Baseline to Week 12 | -2.1 Days | Standard Deviation 2.63 |
Secondary
Summary of Rescue Medication Usage-Open Label Phase
Rescue medication usage (number of days used) during the Open Label Phase.
Time frame: 48 weeks -From baseline to 48 weeks after baseline (Baseline is defined as the last week prior to Visit 14 (Randomization Visit) for the roll-over subjects and the last week prior to Visit 14 (Enrollment Visit) for de novo subjects).
Population: Modified Intent-to-Treat (mITT) Population: The mITT Population consisted of all randomized subjects, with the exception of the subjects from Sites 068 and 077 due to persistent site non-compliance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 8 | -0.301 Days | Standard Deviation 1.75 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 40 | -0.941 Days | Standard Deviation 2.41 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 44 | -1.050 Days | Standard Deviation 2.54 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 12 | -0.472 Days | Standard Deviation 1.99 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 48 | -1.088 Days | Standard Deviation 2.2 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 24 | -0.689 Days | Standard Deviation 1.96 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 20 | -0.562 Days | Standard Deviation 2 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 16 | -0.679 Days | Standard Deviation 1.87 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 4 | -0.744 Days | Standard Deviation 1.54 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 28 | -1.045 Days | Standard Deviation 2.17 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Baseline | 1.172 Days | Standard Deviation 1.99 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 32 | -0.864 Days | Standard Deviation 2.36 |
| CAM2038 (Buprenorphine FluidCrystal®) q1w and q4w | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 36 | -0.989 Days | Standard Deviation 2.29 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 4 | -0.793 Days | Standard Deviation 2.47 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 36 | -0.359 Days | Standard Deviation 1.63 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 8 | -0.671 Days | Standard Deviation 2.18 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 32 | -0.577 Days | Standard Deviation 2.12 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 40 | -0.980 Days | Standard Deviation 2.26 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Baseline | 0.352 Days | Standard Deviation 0.68 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 16 | -0.418 Days | Standard Deviation 2.33 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 44 | -0.767 Days | Standard Deviation 1.9 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 20 | -0.745 Days | Standard Deviation 2.02 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 28 | -0.553 Days | Standard Deviation 1.64 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 48 | -0.929 Days | Standard Deviation 2.15 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 12 | -1.180 Days | Standard Deviation 2.48 |
| Placebo Subcutaneous Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 24 | -0.959 Days | Standard Deviation 2.52 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 24 | -0.933 Days | Standard Deviation 2.64 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Baseline | 1.330 Days | Standard Deviation 2.23 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 4 | -1.124 Days | Standard Deviation 2.32 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 8 | -1.672 Days | Standard Deviation 2.29 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 12 | -1.817 Days | Standard Deviation 2.53 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 20 | -0.490 Days | Standard Deviation 2.48 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 16 | -0.990 Days | Standard Deviation 2.07 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 28 | -0.875 Days | Standard Deviation 2.8 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 32 | -1.280 Days | Standard Deviation 2.7 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 36 | -1.479 Days | Standard Deviation 2.91 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 40 | -1.339 Days | Standard Deviation 2.81 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 44 | -1.465 Days | Standard Deviation 2.51 |
| Rollover Placebo Injections | Summary of Rescue Medication Usage-Open Label Phase | Change from Baseline to Week 48 | -2.302 Days | Standard Deviation 2.89 |