Phase II Pharmacokinetics Study of CAM2038

NCT02710526 | Completed Phase 2 Results

• 1 other identifier: HS-15-549
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

Brief Summary

Phase II, open label, partially randomized, three treatment group study designed to evaluate the steady state pharmacokinetics of buprenorphine and norbuprenorphine following repeated subcutaneous administrations of CAM2038.

Conditions

Opioid Use Disorder; Chronic Pain

Outcome Measures

Primary Outcomes (18)

• 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.

• Area Under the Curve at Steady State (AUC During a 28-day Dosing Interval at Steady State)-Buprenorphine

  Area Under the Curve at steady state (AUC during a 28-day dosing interval at steady state)-Buprenorphine for Pharmacokinetic Population

  PK samples were collected at pre-dose, 0.5, 1, 2, 4, 6, and 10 hours and at approximately 24, 48, 72,96, 120, 168 (7 days), 240 (10 days), 336 (14 days), 504 (21 days) and 672 (28 days) hours after CAM2038 q4w Dose 4

• Average Steady State Concentration-Buprenorphine

  Average steady state concentration-Buprenorphine-Pharmacokinetic Population

  PK samples were collected at pre-dose, 0.5, 1, 2, 4, 6, and 10 hours and at approximately 24, 48, 72,96, 120, 168 (7 days), 240 (10 days), 336 (14 days), 504 (21 days) and 672 (28 days) hours after CAM2038 q4w Dose 4

• Maximum Steady State Concentration-Buprenorphine

  Maximum steady state concentration-BuprenorphinePharmacokinetic (PK) Population

  PK samples were collected at pre-dose, 0.5, 1, 2, 4, 6, and 10 hours and at approximately 24, 48, 72,96, 120, 168 (7 days), 240 (10 days), 336 (14 days), 504 (21 days) and 672 (28 days) hours after CAM2038 q4w Dose 4

• Time to Maximum Concentration at Steady State-Buprenorphine

  Time to maximum concentration at steady state-Buprenorphine Pharmacokinetic (PK) Population

  PK samples were collected at pre-dose, 0.5, 1, 2, 4, 6, and 10 hours and at approximately 24, 48, 72,96, 120, 168 (7 days), 240 (10 days), 336 (14 days), 504 (21 days) and 672 (28 days) hours after CAM2038 q4w Dose 4

• Norbuprenorphine/Buprenorphine Ratios at Maximum Concentration at Steady State

  Norbuprenorphine/buprenorphine ratios at maximum concentration at steady state 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.

• 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.

  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-Norbuprenorphine 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

  Css,av (average plasma concentration during a dosing interval at steady state) for each injection site-Norbuprenorphine-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-Norbuprenorphine-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.

• 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-Norbuprenorphine-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.

• Norbuprenorphine/Buprenorphine Ratios for Area Under the Curve at Steady State

  Norbuprenorphine/buprenorphine ratios for Area Under the Curve at steady state 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.

• Area Under the Curve at Steady State (AUC During a 28-day Dosing Interval at Steady State)-Norepinephrine

  Area Under the Curve at steady state (AUC during a 28-day dosing interval at steady state)-Norepinephrine-Pharmacokinetic (PK) Population

  PK samples were collected at pre-dose, 0.5, 1, 2, 4, 6, and 10 hours and at approximately 24, 48, 72,96, 120, 168 (7 days), 240 (10 days), 336 (14 days), 504 (21 days) and 672 (28 days) hours after CAM2038 q4w Dose 4

• Average Steady State Concentration-Norbuprenorphine

  Average steady state concentration-Norbuprenorphine-Pharmacokinetic (PK) Population

  PK samples were collected at pre-dose, 0.5, 1, 2, 4, 6, and 10 hours and at approximately 24, 48, 72,96, 120, 168 (7 days), 240 (10 days), 336 (14 days), 504 (21 days) and 672 (28 days) hours after CAM2038 q4w Dose 4

• Maximum Steady State Concentration-Norbuprenorphine

  Maximum steady state concentration-Norbuprenorphine-Pharmacokinetic (PK) Population

  PK samples at pre-dose, 0.5, 1, 2, 4, 6,10 hrs and approx. 24, 48, 72, 96, 120, 168, 240, 336, 504 and 672 hrs after CAM2038 q4w Dose 4 and pre-dose (within 45 mins), 10, 20, 30 and 40 mins, and 1, 1.5, 2, 3, 4, 6, 10, and 24 hrs after SL BPN dose 7

• Time to Maximum Concentration at Steady State-Norbuprenorphine

  Time to maximum concentration at steady state-Norbuprenorphine-Pharmacokinetic (PK) Population

  PK samples at pre-dose, 0.5, 1, 2, 4, 6,10 hrs and approx. 24, 48, 72, 96, 120, 168, 240, 336, 504 and 672 hrs after CAM2038 q4w Dose 4 and pre-dose (within 45 mins), 10, 20, 30 and 40 mins, and 1, 1.5, 2, 3, 4, 6, 10, and 24 hrs after SL BPN dose 7

Secondary Outcomes (1)

• Number of Participants With Adverse Events for Both Weekly and Monthly CAM2038

  99 days for Group 1, 162 days for Group 2, 127 days for Group 3

Other Outcomes (3)

• Summary of Average Daily Pain by Week (ITT Population)

  99 days for Group 1, 162 days for Group 2, 127 days for Group 3

• Number of Participants With Confirmed Opiate Independence as Confirmed by Negative Urine Toxicology Tests

  99 days for Group 1, 162 days for Group 2, 127 days for Group 3

• Subject-rated Worst Daily Pain

  99 days for Group 1, 162 days for Group 2, 127 days for Group 3

Study Arms (3)

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

CAM2038 DRUG

Long-Acting Subcutaneous Injectable Depot of Buprenorphine

Also known as: Buprenorphine

128 mg CAM2038 monthly injection; 160 mg CAM2038 monthly injection; 32 mg CAM2038 weekly

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Braeburn Pharmaceuticals: lead

Study Sites (3)

Parkway Medical

Birmingham, Alabama, 35215, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

The Rivus Wellness & Research Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Related Publications (1)

• 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.

  PMID: 37584841 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders; Chronic Pain

Interventions

Buprenorphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Sonnie Kim
• Organization: Braeburn Inc

sonnie@braeburnrx.com

6104678718

Study Officials

• James Sullivan

  Parkway Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 16, 2016
• Study Start: February 1, 2015
• Primary Completion: May 17, 2017
• Study Completion: July 3, 2017
• Last Updated: April 30, 2020
• Results First Posted: April 30, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)