A Phase I, randomized, open-label, active-controlled, three-way treatment trial assessing pharmacokinetics, bioavailability and safety of three doses of CAM2038 q1w (once-weekly) (buprenorphine FluidCrystal® injection depot), versus active comparators, intravenous and sublingual buprenorphine, in healthy volunteers under naltrexone blockage

Phase 1

Completed

• Conditions: Treatment of opioid dependence; Mental and Behavioural Disorders; Mental and behavioural disorders due to use of opioids

• Registration Number: ISRCTN41550730
• Lead Sponsor: Camurus AB (Sweden)

Brief Summary

2018 results in https://pubmed.ncbi.nlm.nih.gov/29102550/ (added 12/02/2021)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2014-04-30
• Study Start: 2014-05-19
• Last Update Posted: 22 February 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Participants who meet the following criteria will be considered suitable to participate in the clinical study:
1. Are able to provide written informed consent to participate in the trial and able to understand the procedures and trial requirements
2. Are healthy adult male or female, =18 and =65 years of age at the time of signing of informed consent
3. Body mass index (BMI) range of 18.5 to 30.0 kg/m2, inclusive, and body mass of at least 50 kg
4. If female and of childbearing potential, is not lactating and not pregnant (has negative pregnancy test results at screening)
5. If female, is of non-childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or practicing one of the following medically acceptable methods of birth control and agrees to continue with the regimen throughout the trial:
5.1. Oral, implantable, or injectable contraceptives for 3 consecutive months before screening, in combination with a condom
5.2. Intrauterine device (IUD) in combination with a condom
5.3. Double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream)
6. Are willing and able to comply with the trial requirements and complete the trial assessments (e.g., providing urine sample under observation, completing questionnaires, abstaining from activities that require focused attention, e.g., driving a car or other vehicles, operating machines or engaging in potentially dangerous activities that require focused attention and intact physical balance during the study)

Exclusion Criteria

Participants who meet one or more of the following criteria will not be considered eligible to participate in the clinical study:
1. Have a known contraindication or hypersensitivity to buprenorphine or other opioids.
2. Have any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated asymptomatic, seasonal allergies).
3. Have any clinically significant laboratory test result that, in the opinion of the investigator, could compromise the participant's welfare, ability to communicate with the trial staff, or otherwise contraindicate trial participation.
4. Have any clinically significant unstable cardiac, respiratory, neurological, immunological, endocrinological, hematological, bile duct, urological or renal disease or any other condition that, in the opinion of the investigator, could compromise the participant's welfare, ability to communicate with the trial staff, or otherwise contraindicate trial participation.
5. Current use of agents metabolized through Cytochrome P450 3A4 (CYP 3A4) such as azole, antifungals (e.g. ketoconazole), macrolide antibiotics (e.g. erythromycin), or protease inhibitors (e.g. ritonavir, indinavir and saquinavir).
6. Current dependence (by DSM-IV criteria) of any psychoactive substance other than opiates, caffeine or nicotine dependence.
7. Prior or current enrolment in an opiate substitution or addiction rehabilitation program (i.e. methadone, levoalphaacetylmethadol).
8. Have tested positive for human immunodeficiency virus (HIV). Participants with hepatitis infection and no significant viral load, no acute signs of inflammation, and no clinical necessity for therapy will be allowed.
9. Are considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator?s Brochure for CAM2038 50 mg/mL q1w [buprenorphine FluidCrystal® injection depot]), to be an unsuitable candidate to receive the trial medication.
10. Have any other condition or deviation that, in the opinion of the investigator, makes the participant unsuitable for participation in the trial.
11. 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.
12. Veins unsuitable for repeat venipuncture.
13. Any condition requiring regular concomitant medication including herbal products, or predicted need of any concomitant medication during the study.
14. Intake of any medication (except paracetamol [up to 2 g per day]) including over-the-counter (OTC) medication, herbal and dietary supplements such as St John?s Wort, vitamins and minerals that could affect the outcome of the study, within 2 weeks before the first administration of the IMP or less than 5 times the half-life of that medication, whichever is the longer.
15. A pulse of <40 bpm or >90 bpm; mean systolic blood pressure (SBP) <90 mmHg or >140 mmHg; mean diastolic blood pressure (DBP) <40 mmHg or >90 mmHg (triplicate measurements, resting in supine position for

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Pharmacokinetics sampling times:<br> 1.1. Single IV buprenorphine injection on Day 1: predose (within 45 minutes) and at 5, 10, 15, 20, 30 and at 40 minutes, and at 1, 1.5, 2, 4, 6, 10 and 24 hours post dosing.<br> 1.2. Buprenorphine: sublingual 8 mg, 16 mg or 24 mg: predose (within 45 minutes) and at 10, 20, 30 and 40 minutes and at 1, 1.5, 2, 3, 4, 6, 10 and 24 hours post dosing for the 1st dose and 7th dose, and additionally at 48 and<br> 72 hours post dosing for the 7th dose.<br> 1.3. CAM2038 50 mg/mL q1w 8 mg, 16 mg and 32 mg: predose (within 45 minutes) and at 0.5, 1, 2, 4, 6, 10, 24, 36 and 48 hours post dosing, subcutaneous injection: and at 3, 4, 5, 7, 14, 21 and 28 days post dose.<br>