Phase 2
Completed N=66
Phase II Pharmacokinetics Study of CAM2038
Source: ClinicalTrials.gov NCT02710526 ↗Enrolled (actual)
66
Serious AEs
0.0%
Results posted
Apr 2020
Primary outcomePrimary: 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 — 700; 657; 613; 591 ng*h/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
700; 657; 613; 591 | — |
| PRIMARY Css,av(Average Plasma Concentration During a Dosing Interval at Steady State) for Each Injection Site for the Evaluable Pharmacokinetic (PKEVAL) Population |
4.17; 3.91; 3.65; 3.52 | — |
| PRIMARY Css,Max (Maximum Observed Plasma Concentration During a Dosing Interval at Steady State) for Each Injection Site. |
1.85; 1.78; 1.74; 1.84 | — |
| PRIMARY Tss,Max (Time to Maximum Concentration at Steady State) for Each Injection Site |
72.0; 72.0; 72.0; 30.0 | — |
| PRIMARY Area Under the Curve at Steady State (AUC During a 28-day Dosing Interval at Steady State)-Buprenorphine |
2610; 3540 | — |
| PRIMARY Average Steady State Concentration-Buprenorphine |
3.89; 5.27 | — |
| PRIMARY Maximum Steady State Concentration-Buprenorphine |
11.1; 15.4; 11.1 | — |
| PRIMARY Time to Maximum Concentration at Steady State-Buprenorphine |
10.0; 24.0; 1.69 | — |
| PRIMARY Norbuprenorphine/Buprenorphine Ratios at Maximum Concentration at Steady State |
0.305; 0.307; 0.366; 0.366 | — |
| 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. |
204; 192; 208; 197 | — |
| PRIMARY Css,av(Average Plasma Concentration During a Dosing Interval at Steady State) for Each Injection Site |
1.22; 1.15; 1.24; 1.17 | — |
| PRIMARY Norbuprenorphine/Buprenorphine Ratios for Area Under the Curve at Steady State |
0.354; 0.341; 0.355; 0.370 | — |
| PRIMARY Area Under the Curve at Steady State (AUC During a 28-day Dosing Interval at Steady State)-Norepinephrine |
795; 1590 | — |
| PRIMARY Average Steady State Concentration-Norbuprenorphine |
1.18; 2.37 | — |
| PRIMARY Maximum Steady State Concentration-Norbuprenorphine |
2.14; 4.61; 7.92 | — |
| PRIMARY Time to Maximum Concentration at Steady State-Norbuprenorphine |
84.1; 121; 1.78 | — |
| SECONDARY Number of Participants With Adverse Events for Both Weekly and Monthly CAM2038 |
14; 10; 9; 0; 0; 0 | — |
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 a
Data sourced from ClinicalTrials.gov (NCT02710526). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.