Phase II Pharmacokinetics Study of CAM2038 | NCT02710526

NCT02710526

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
32 mg CAM2038 weekly	Experimental	Group 1, 32 mg of CAM2038 subcutaneous weekly injection at multiple injection sites	Drug: CAM2038
128 mg CAM2038 monthly injection	Experimental	Group 2: 128 mg of CAM2038 subcutaneous monthly injection in the buttocks	Drug: CAM2038
160 mg CAM2038 monthly injection	Experimental	Group 3: 24mg sublingual BPN for the first 7 days, and then 160 mg of CAM2038 subcutaneous monthly injection in the buttocks starting on Day 8.	Drug: CAM2038

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CAM2038	Drug	Long-Acting Subcutaneous Injectable Depot of Buprenorphine	128 mg CAM2038 monthly injection 160 mg CAM2038 monthly injection 32 mg CAM2038 weekly

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
AUCss(Area Under the Plasma Concentration-time Curve During a 7-day Dosing Interval at Steady State) for Each Injection Site, i.e., Buttock (Reference), Abdomen, Thigh and Back of Upper Arm for the Evaluable Pharmacokinetic (PKEVAL) Population	AUCss (area under the plasma concentration-time curve during a 7-day dosing interval at steady state) for each injection site, i.e., buttock (reference), abdomen, thigh and back of upper arm-Buprenorphine for the Evaluable Pharmacokinetic (PKEVAL) Population	PK samples were collected at pre-dose and at 0.5, 1, 2, 4, 6, 10, 24, 30, 48, 72, 96, 120 and 168 hours post-CAM2038 q1w for Doses/Weeks 4, 5, 6, and 7.
Css,av(Average Plasma Concentration During a Dosing Interval at Steady State) for Each Injection Site for the Evaluable Pharmacokinetic (PKEVAL) Population	Css,av (average plasma concentration during a dosing interval at steady state) for each injection site-Buprenorphine for the Evaluable Pharmacokinetic (PKEVAL) Population	PK samples were collected at pre-dose and at 0.5, 1, 2, 4, 6, 10, 24, 30, 48, 72, 96, 120 and 168 hours post-CAM2038 q1w for Doses/Weeks 4, 5, 6, and 7.
Css,Max (Maximum Observed Plasma Concentration During a Dosing Interval at Steady State) for Each Injection Site.	Css,max (maximum observed plasma concentration during a dosing interval at steady state) for each injection site-Buprenorphine	PK samples were collected at pre-dose and at 0.5, 1, 2, 4, 6, 10, 24, 30, 48, 72, 96, 120 and 168 hours post-CAM2038 q1w for Doses/Weeks 4, 5, 6, and 7.
Tss,Max (Time to Maximum Concentration at Steady State) for Each Injection Site	Tss,max (time to maximum concentration at steady state) for each injection site-buprenorphine	PK samples were collected at pre-dose and at 0.5, 1, 2, 4, 6, 10, 24, 30, 48, 72, 96, 120 and 168 hours post-CAM2038 q1w for Doses/Weeks 4, 5, 6, and 7.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events for Both Weekly and Monthly CAM2038	Number of Participants with Adverse Events for Both weekly and monthly CAM2038-Safety Population	99 days for Group 1, 162 days for Group 2, 127 days for Group 3

Other Outcomes

Measure	Description	Time Frame
Summary of Average Daily Pain by Week (ITT Population)	Summary of Average Daily Pain, using an 11-point Numerical Rating Scale (NRS) for pain, following repeated subcutaneous administration of CAM2038 weekly and CAM2038 monthly in adult opioid-dependent subjects. 11 point scale ranging from 0-10, with 0 being the least amount of pain to 10 being the worst pain imaginable. (ITT Population)	99 days for Group 1, 162 days for Group 2, 127 days for Group 3

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject must provide written informed consent prior to the conduct of any study related procedures.
Male or non pregnant, non lactating female subject, aged 19 to 65 years, inclusive.
Body mass index between 19 and 35 kg/m2, inclusive.
Current diagnosis of moderate to severe opioid use disorder (according to the DSM 5) or past medical history of opioid use disorder currently being treated with SL BPN.
Subject must be taking SL BPN (Subutex® equivalent) 24 mg (Group 1 and Group 2) or ≥24 mg (Group 3) daily for at least 30 days prior to Screening.
Subject has a history of moderate to severe chronic non cancer pain.
Male and female subjects of childbearing potential must be willing to use a reliable method of contraception during the entire study (Screening visit to Follow-up phone call).
Subject must be willing and able to comply with all study procedures and requirements.

Exclusion Criteria:

Individuals meeting DSM-V substance use disorder criteria for alcohol, benzodiazepines, central nervous system (CNS) stimulants, or other drugs of abuse (excluding caffeine, tobacco or THC/marijuana).
Any clinically significant abnormality on the basis of medical history, vital signs, physical examination, 12-lead electrocardiogram (ECG; Fridericia's corrected QT interval [QTcF] ≥450 msec. for males or ≥470 msec. for females), and laboratory evaluations (including hematology, clinical chemistry, urinalysis at Screening), in the opinion of the Investigator.
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, including subjects who are at a risk for gastrointestinal obstruction or paralytic ileus or who have severe respiratory insufficiency, respiratory depression, airway obstruction, gastrointestinal motility disorders, biliary tract disease, severe hepatic insufficiency, planned surgery and prior treatment with monoamine oxidase inhibitors.
Use (therapeutic or non-therapeutic) of opioids other than SL BPN.
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.
Pregnant or lactating or planning to become pregnant during the study.
Diagnosis of, or currently under investigation for, fibromyalgia, complex regional pain syndrome, neurogenic claudication due to spinal stenosis, spinal cord compression, acute nerve root compression, severe or progressive lower extremity weakness or numbness.
History of chemotherapy or confirmed malignancy (except basal cell or squamous carcinoma of the skin) within the past 2 years.
Clinically significant history of, or current evidence for, suicidal ideation or those who are actively suicidal, as based on the Columbia-Suicide Severity Rating Scale (C-SSRS; grade 4 or 5).
Clinically significant history of major depressive disorder that is poorly controlled with medication.
Hypersensitivity or allergy to BPN or other opioids, or excipients of CAM2038.
Exposure to any investigational drug within the 4 weeks prior to Screening.
Participants with a clinically significant history of risk factors of Torsades de Pointes and any existing ventricular tachyarrhythmias such as bigeminy, trigeminy, heart failure, hypokalemia, family history of Long QT Syndrome.
On medications that have the potential for prolonging the QT interval or who may require such medications during the course of the study along with clinically significant abnormalities on screening electrocardiogram (ECG) readings as deemed by the investigator.
Requires current use of agents that are 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).
Intolerance to venipuncture and/or difficulty with venous access, as per the judgment of the Investigator/research staff.
Is an employee of the Investigator or the study site, with direct involvement in the proposed study or other studies under the direction of the Investigator or study site, or is a family member of an employee or of the Investigator.
Any pending legal action that could prohibit participation or compliance in the study.

Contacts/Locations Module

Name	Affiliation	Role
James Sullivan	Parkway Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Parkway Medical		Birmingham	Alabama	35215	United States
Hassman Research Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37584841	Derived	Bjornsson M, Acharya C, Strandgarden K, Tiberg F. Population Pharmacokinetic Analysis Supports Initiation Treatment and Bridging from Sublingual Buprenorphine to Subcutaneous Administration of a Buprenorphine Depot (CAM2038) in the Treatment of Opioid Use Disorder. Clin Pharmacokinet. 2023 Oct;62(10):1427-1443. doi: 10.1007/s40262-023-01288-6. Epub 2023 Aug 16.

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	32 mg CAM2038 Weekly	Group 1, 32 mg of CAM2038 subcutaneous weekly injections at multiple injection sites CAM2038: Long-Acting Subcutaneous Injectable Depot of Buprenorphine
FG001	128 mg CAM2038 Monthly Injection	Group 2: 128 mg of CAM2038 subcutaneous monthly injections during Treatment Phase and 32 mg of CAM2038 subcutaneous weekly injections during Safety Extension in the buttocks CAM2038: Long-Acting Subcutaneous Injectable Depot of Buprenorphine
FG002	160 mg CAM2038 Monthly Injection	Group 3: 24 mg SL BPN for the first 7 days and then 160 mg of CAM2038 subcutaneous monthly injections in the buttocks starting on Day 8 CAM2038: Long-Acting Subcutaneous Injectable Depot of Buprenorphine

Periods

Title

Milestones

Reasons Not Completed

Treatment Phase

Type	Comment	Milestone Data
STARTED		FG00028 subjects FG00120 subjects FG00218 subjects
COMPLETED		FG00022 subjects FG00116 subjects FG00212 subjects
NOT COMPLETED		FG0006 subjects FG0014 subjects FG0026 subjects

Safety Extension

Type	Comment	Milestone Data
STARTED		FG00015 subjects FG00112 subjects FG0020 subjects
COMPLETED		FG000

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	32 mg CAM2038 Weekly	Group 1, 32 mg of CAM2038 subcutaneous weekly injection at multiple injection sites CAM2038: Long-Acting Subcutaneous Injectable Depot of Buprenorphine
BG001	128 mg CAM2038 Monthly Injection

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

AUCss(Area Under the Plasma Concentration-time Curve During a 7-day Dosing Interval at Steady State) for Each Injection Site, i.e., Buttock (Reference), Abdomen, Thigh and Back of Upper Arm for the Evaluable Pharmacokinetic (PKEVAL) Population

AUCss (area under the plasma concentration-time curve during a 7-day dosing interval at steady state) for each injection site, i.e., buttock (reference), abdomen, thigh and back of upper arm-Buprenorphine for the Evaluable Pharmacokinetic (PKEVAL) Population

Evaluable Pharmacokinetic (PKEVAL) Population consisted of all subjects who had sufficient PK data for all 4 randomized injection sites to derive PK parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

PK samples were collected at pre-dose and at 0.5, 1, 2, 4, 6, 10, 24, 30, 48, 72, 96, 120 and 168 hours post-CAM2038 q1w for Doses/Weeks 4, 5, 6, and 7.

ID	Title	Description
OG000	32 mg CAM2038 Weekly-Buttock

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	32 mg CAM2038 Weekly	Group 1, 32 mg of CAM2038 subcutaneous weekly injection at multiple injection sites CAM2038: Long-Acting Subcutaneous Injectable Depot of Buprenorphine

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial Fibrillation	Cardiac disorders		Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Sonnie Kim	Braeburn Inc	6104678718		sonnie@braeburnrx.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Dec 16, 2016	Sep 13, 2018	SAP_000.pdf
Prot	Yes	No	No	Study Protocol	Oct 5, 2016	Sep 13, 2018	Prot_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009293	Opioid-Related Disorders
D059350	Chronic Pain

ID	Term
D000079524	Narcotic-Related Disorders
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders
D001523	Mental Disorders

Intervention Browse Module

ID	Term
D002047	Buprenorphine

ID	Term
D009019	Morphinans
D053610	Opiate Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds

Masking Info

Group 2: 128 mg of CAM2038 subcutaneous monthly injection in the buttocks

CAM2038: Long-Acting Subcutaneous Injectable Depot of Buprenorphine

Group 1, 32 mg of CAM2038 subcutaneous weekly injection at Buttock

CAM2038: Long-Acting Subcutaneous Injectable Depot of Buprenorphine

EG0000 events0 affected28 at risk

EG0011 events1 affected20 at risk

EG0020 events0 affected17 at risk

EG0030 events0 affected18 at risk