Fentanyl Blockade Study in OT patients

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1. Signed the ICF and able to comply with the requirements and restrictions listed therein;
2. Male and female, age 18 to 55 years, inclusive;
3. Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative pregnancy test prior to enrolment and must agree to use a medically acceptable means of contraception from screening through at least 3 months after the last dose of study drug.
4. BMI 18 to 32 kg/m2, inclusive;
5. Opioid-tolerant patients administered opioids at daily doses = 60 mg oral morphine equivalents
6. Stable as defined by the Investigator, based on a medical evaluation that includes the patient’s medical and surgical history, physical examination, vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis;
7. No current use of any CNS depressants, besides opioids, prescribed or otherwise for 5 half-lives of the product before first study drug administration unless assessed as safe by the principal investigator

Exclusion Criteria

1. Clinically significant risk factors of Torsades de Pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome) or an ECG demonstrating a Fridericia’s corrected QT interval (QTcF) > 450 msec in males and QTcF > 470 msec in females at screening;
2. Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than opioids, caffeine, or nicotine;
3. Any active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints (including sleep apnoea, other significant respiratory illness, history or risk of difficult intubation, limited cervical spine mobility or limited oral excursion);
4. Not able to abstain from smoking cigarettes during each dose administration day;
5. Consume, on average, >27 units/week of alcohol in men and >20 units/week of alcohol in women (1 unit = 1 glass (250 mL) beer, 125 mL glass of wine or 25 mL of 40% spirit);
6. Use of buprenorphine 10 days prior to the first study drug administration;
7. Use of prescription or OTC medications that are clinically relevant CYP P450 3A4 or CYP P450 2D6 inducers or inhibitors from 14 days prior to study drug administration;
8. History of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent;
9. Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg prior to Day 1;
10. History or presence of allergic response to buprenorphine or fentanyl;
11. Opioid-tolerant patients who have demonstrated allergic reactions (e.g., food, drug, atopic reactions or asthmatic episodes) which, in the opinion of the Investigator and sponsor, interfere with their ability to participate in the trial.
12. Estimated glomerular filtration rate <60 mL/min as estimated by the CKD-EPI equation;
13. Clinical significant anaemia at screening or donation of > 250 mL of blood or plasma within the last 3 months;
14. Positive serology tests for HIV, acute hepatitis B, or acute hepatitis C (OT patients with asymptomatic hepatitis B or C infection may be enrolled);
15. AST or ALT levels >3.0 times the upper limit of normal at screening;
16. Any current, clinically significant, known medical condition in particular any existing conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud’s disease, urticaria, hypothyroidism);
17. Treatment with another investigational drug within 3 months prior to dosing or having participated in more than 4 investigational drug studies within 1 year prior to screening;
18. Site staff or subjects affiliated with, or a family member of, site staff directly involved in the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
• Thermal pain: PDT (°C)<br>• Pressure Pain: PDT (kPa), PTT (kPa), area-under-the-curve (AUC) (kPamm) and post-test VAS (mm)<br>• Electrical Burst: PDT (mA), PTT (mA), AUC (mAmm) and post-test VAS (mm)<br>• Electrical Stair: PDT (mA), PTT (mA), AUC (mAmm) and post-test VAS (mm)<br>• Cold Pressor: pain detection threshold (PDT) (s), area-above-the-curve (AAC) (smm) and post-test visual analogue scale (VAS) (mm)

Secondary Outcome Measures

Name	Time	Method
• Saccadic eye movement<br>o saccadic reaction time (s),<br>o saccadic peak velocity (°/s), and<br>o saccadic inaccuracy (%);<br>• Smooth pursuit eye movements:<br>o percentage of time the eyes of the subjects are in smooth pursuit of the target (%);<br>• Body sway:<br>o antero-posterior sway (mm);<br>• Adaptive tracking:<br>o average performance (%);<br>• Pupillometry (mm)<br>• VAS Bond & Lader (Alertness, mood, calmness) (mm)<br>• VAS Bowdle (internal perception, external perception, ‘feeling high’) (mm)<br>• ARCI-49<br><br>Exploratory<br>• Treatment-emergent (serious) adverse events ((S)AEs)<br>• Concomitant medication throughout the study at every study visit<br>• Pharmacokinetic parameters such as Cmax and AUC