Long-Term Safety Study of Buprenorphine (CAM2038) in Adult Outpatients With Opioid Use Disorder

An Open-Label Multicenter Study Assessing the Long-Term Safety of a Once-Weekly and Once-Monthly, Long-Acting Subcutaneous Injection Depot of Buprenorphine (CAM2038) in Adult Outpatients With Opioid Use Disorder

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02672111

Enrollment

228

Registered

2016-02-03

Start date

2015-11-30

Completion date

2017-05-31

Last updated

2020-05-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Opioid Use Disorder

Brief summary

Detailed description

Open-label multi-center, 48 week safety study, consistent with standard practice for long-term safety studies. This one year safety study will utilize CAM2038 q1w (once weekly) and q4w (once monthly) and will have 3 phases: Screening, Treatment, and Follow-up. Patients who are currently taking sublingual (SL) BPN (weekly or monthly prescription visits) or individuals who are actively seeking BPN treatment but who have not yet begun a treatment regimen, may be eligible for the study. Following Screening, qualified subjects meeting inclusion criteria and not meeting exclusion criteria will be initiated on either CAM2038 q1w or q4w, based on their current treatment status (qualified subjects currently on SL BPN or seeking BPN treatment). Qualified subjects will be initiated or transitioned to CAM2038 q1w or q4w as follows: Initiation of BPN treatment - initiate with CAM2038 q1w Currently receiving SL BPN treatments - transfer to corresponding CAM2038 q1w or q4w dose

Interventions

DRUGCAM2038 q1w or q4w exposure to SL BPN/NX

DRUGCAM2038 q1w or q4w new to BPN treatment

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

1. Subject must provide written informed consent prior to the conduct of any study-related procedures. 2. Male or female, 18-65 years of age, inclusive. 3. Female subjects of childbearing potential must be willing to use a highly effective method of contraception during the entire study (Screening Visit to Follow-Up Visit). 4. Current diagnosis of moderate or severe opioid use disorder (DSM-V) or past medical history of opioid use disorder currently being treated with SL BPN. 5. Considered by the Investigator to be a good candidate for BPN treatment, based on medical and psychosocial history. 6. Subjects must meet one of the following criteria for BPN treatment history: * Voluntarily seeking treatment for opioid use disorder (not currently on BPN treatment for at least last 60 days but seeking BPN treatment), or; * Currently on SL BPN treatment.

Exclusion criteria

1. Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS). 2. Current diagnosis of chronic pain requiring opioids for treatment. 3. Current DSM-V diagnosis for moderate to severe substance use disorder (including alcohol) other than opioids, caffeine or nicotine and currently being treated as the primary substance use disorder. 4. Recent history of or current evidence of suicidal ideation or active suicidal behavior as based on the Columbia Suicide Severity Rating Scale (C-SSRS) (Yes responses to questions 4 or 5). 5. Pregnant or lactating or planning to become pregnant during the study. 6. Hypersensitivity or allergy to naloxone (only for subjects receiving the SL BPX test dose), BPN or excipients of CAM2038. 7. Requires chronic use of agents that are strong inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4) such as some azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., clarithromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir). 8. Hepatitis, unless under stable treatment, at the discretion of the Investigator. 9. Any pending legal action that could prohibit participation or compliance in the study. 10. Exposure to any investigational drug within the 4 weeks prior to Screening. 11. Aspartate aminotransferase (AST) levels ≥3 X the upper limit of normal, alanine aminotransferase (ALT), levels ≥ 3 X the upper limit of normal, total bilirubin ≥ 1.5 X the upper limit of normal, or creatinine ≥ 1.5 X upper limit of normal on the Screening laboratory assessments, or other clinically significant laboratory abnormalities, which in the opinion of the Investigator may prevent the subject from safely participating in study. 12. Participants with a history of risk factors of Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or an ECG demonstrating a Fridericia's corrected QT interval (QTcF) \>450 msec in males and QTcF \> 470 in females at screening. 13. 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 study. This includes, but is not limited to, subjects with attention deficit hyperactivity disorder receiving central stimulants (e.g. methylphenidate or other central stimulants), as well as subjects with severe respiratory insufficiency, respiratory depression, airway obstruction, gastrointestinal motility disorders, severe hepatic insufficiency, planned surgery and prior treatment with monoamine oxidase inhibitors. 14. 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 an employee or of the Investigator.

Design outcomes

Primary

Measure	Time frame	Description
Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	12 months- 48 week	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period. Safety Assessments: Adverse events (AEs) and serious adverse events (SAEs)-Overall Safety Population
Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	12 months- 48 week	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period. Safety Assessments: Adverse events (AEs) and serious adverse events (SAEs)-Full Exposure Safety Population

Secondary

Measure	Time frame	Description
Summary of Retention in Treatment (Efficacy Population)	48 weeks of treatment	The following is a summary of treatment retention over 48 weeks
Summary of Clinical Opiate Withdrawal Scale (COWS) at Selected Time Points (Efficacy Population)	12 months- 48 week	A summary of COWS (administered by the Clinician) over 48 weeks to show withdrawal symptoms from baseline to end of treatment. This scale consists of 11 common opiate withdrawal signs or symptoms, rated on a numeric scale from 0 to 4 or 5 and based on a timed period of observation of the subject by the rater. Higher scores are associated with greater withdrawal symptoms with a total range for all items of between 0-48
Mean Percentage of Negative Urine Toxicology Results for Illicit Opioid Use Supported by Self Reported Illicit Opioid Use (Efficacy Population)	12 months (48 weeks)	The following is a summary of Mean Percentage of Negative Urine Toxicology Results for Illicit Opioid Use Supported by Self Reported Illicit Opioid Use (Efficacy Population)
Summary of Desire to Use Visual Analog Scale (VAS) at Selected Time Points (Efficacy Population)	12 months- 48 week	The following table summarizes the desire to use measurements over a period of 12 months - 48 weeks. Desire to Use assessments were administered using a unipolar 100 mm VAS. Subjects were asked Since your last scheduled assessment visit, indicate your worst or strongest desire to use opioids, where 0 = No desire to use and 100 mm = Strongest possible desire.
Summary of Need to Use Visual Analog Scale (VAS) at Selected Time Points (Efficacy Population)	12 months- 48 week	The following results summarize the need to use VAS over a period of 12 months - 48 weeks. Need to Use assessments were administered using a unipolar 100 mm VAS. Subjects were asked Since your last scheduled assessment visit, indicate your worst or strongest need to use opioids, where 0 = No need to use and 100 mm = Strongest possible need.
Summary of Subjective Opiate Withdrawal Scale (SOWS) at Selected Time Points (Efficacy Population)	12 months- 48 week	Summary of SOWS over time to show withdrawal symtons, from baseline to end of treatment. This form contains 16 questions that rate the intensity of withdrawal from 0 (Not at all) to 4 (Extremely), with higher scores associated with greater withdrawal symptoms and total range for all items of 0-64
Mean Percentage of Self-reported No Illicit Opioid Use (Efficacy Population)	12 months (48 weeks)	The following is a summary of Mean Percentage of Self-Reported No Illicit Opioid Use during the entire study (Efficacy Population). The proportion of patients who reported no illicit opioid use during the study was analyzed. For example if a subject provided 10 self reports and 2 out of the 10 were Used, the percentage for the subject would be 20%. The average percentage of all patients is provided.

Countries

Australia, Denmark, Germany, Hungary, Sweden, Taiwan, United Kingdom, United States

Participant flow

Pre-assignment details

One patient enrolled in the study but did not receive CAM2038

Participants by arm

Arm	Count
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX Subjects previously exposed to SL BPN/NX who received CAM2038 q1w or q4w	190
CAM2038 q1w or q4w New to BPN Treatment New to BPN Treatment who received CAM2028 q1w or q4w	37
Total	227

Baseline characteristics

Characteristic	CAM2038 q1w or q4w New to BPN Treatment	Total	CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX
Age, Continuous	41.8 years	41.4 years	41.3 years
BMI (kg/m^2)	25.3 kg/m^2	26.5 kg/m^2	26.7 kg/m^2
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	4 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants	222 Participants	187 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	17 Participants	20 Participants	3 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	4 Participants	4 Participants
Race (NIH/OMB) White	20 Participants	203 Participants	183 Participants
Region of Enrollment Australia	1 Participants	24 Participants	23 Participants
Region of Enrollment Europe	0 Participants	76 Participants	76 Participants
Region of Enrollment United States	36 Participants	127 Participants	91 Participants
Sex: Female, Male Female	13 Participants	84 Participants	71 Participants
Sex: Female, Male Male	24 Participants	143 Participants	119 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 190	0 / 37
other Total, other adverse events	131 / 190	11 / 37
serious Total, serious adverse events	13 / 190	2 / 37

Outcome results

Primary

Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population

Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period. Safety Assessments: Adverse events (AEs) and serious adverse events (SAEs)-Full Exposure Safety Population

Time frame: 12 months- 48 week

Population: Full Exposure Safety Population-Subjects treated with CAM2038

Arm	Measure	Group	Value (NUMBER)
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 TEAE	95 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 drug-related TEAE	41 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 severe TEAE	11 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Deaths	0 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 non-fatal SAE	8 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 non-fatal drug related SAE	0 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Hospitalizations	7 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject discontinued study drug due to a TEAE	0 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject discontinued study drug due to a TEAE	0 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 TEAE	8 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 non-fatal SAE	1 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 drug-related TEAE	1 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Hospitalizations	1 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 severe TEAE	1 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Subject had at least 1 non-fatal drug related SAE	0 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population	Deaths	0 participants

Primary

Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population

Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period. Safety Assessments: Adverse events (AEs) and serious adverse events (SAEs)-Overall Safety Population

Time frame: 12 months- 48 week

Population: Overall Safety Population-Subjects treated with CAM2038

Arm	Measure	Group	Value (NUMBER)
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 TEAE	131 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 drug-related TEAE	58 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 severe TEAE	13 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Deaths	0 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 non-fatal SAE	10 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 non-fatal drug related SAE	0 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Hospitalizations	9 participants
CAM2038 q1w or q4w With Prior Exposure to SL BPN/NX	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject discontinued study drug due to a TEAE	4 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject discontinued study drug due to a TEAE	1 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 TEAE	12 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 non-fatal SAE	2 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 drug-related TEAE	2 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Hospitalizations	1 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 severe TEAE	2 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Subject had at least 1 non-fatal drug related SAE	0 participants
CAM2038 q1w or q4w New to BPN Treatment	Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population	Deaths	0 participants

Secondary

Mean Percentage of Negative Urine Toxicology Results for Illicit Opioid Use Supported by Self Reported Illicit Opioid Use (Efficacy Population)

The following is a summary of Mean Percentage of Negative Urine Toxicology Results for Illicit Opioid Use Supported by Self Reported Illicit Opioid Use (Efficacy Population)

Time frame: 12 months (48 weeks)