Pain Pain
Conditions
Interventions
Investigational drug
4-hour (part 1) and 48-hour (part 2) continuous i.v. infusion of STR-324 or
placebo. In part 1, a total of 8 dose levels will be administered in 40 mL
during a 4-hour infusion.
Sponsors
Stragen France
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to any study-mandated procedure 2. Healthy male subjects, 18 to 45 years of age, inclusive at screening. 3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg. 4. All males must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment. 5. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator [(following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature), 12-lead electrocardiogram (ECG)]. Minor deviations of laboratory values from the normal range may be accepted, if judged by the Investigator to have no clinical relevance. 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel, coagulation and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. 3. Abnormal renal function (eGFR (MDRD) 450 or 100 bpm) - Evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker 9. Use of any medications (prescription or over-the-counter [OTC]), within 14 days of study drug administration, or less than 5 half-lives (whichever is longer). Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor. No exceptions will be made for known analgesics (e.g. paracetamol or ibuprofen) 10. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days of study drug administration, or less than 5 half-lives (whichever is longer). Exceptions will only be made if the rationale is clearly documented by the investigator. 11. Participation in an investigational drug or device study within 3 months prior to first dosing. 12. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillizers, or any other addictive agent. 13. Positive test for drugs of abuse at screening or pre-dose. 14. Positive alcohol breath test at screening or pre-dose. Alcohol will not be allowed from at least 24 hours before screening or pre-dose. 15. Smoker of more than 5 cigarettes per day prior to screening or who use tobacco products equivalent to more than 5 cigarettes per day and unable to abstain from smoking whilst in the unit. 16. Is demonstrating excess in xanthine consumption (more than eight cups of coffee or equivalent per day) 17. Any confirmed significant allergic reactions (urticaria or anaphylaxi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability / safety endpoints Treatment-emergent (serious) adverse events ((S)AEs) will be documented, regarding incidence, nature and severity from the time the subject signs the consent until the follow-up visit (End of Study Visit). The following endpoints will be determined at time points indicated in the Schedule of Assessments. * Clinical laboratory tests o Hematology o Chemistry o Coagulation o Urinalysis * Vital signs (supine and standing) o Pulse Rate (bpm) o Systolic blood pressure (mmHg) o Diastolic blood pressure (mmHg) o Respiratory rate o SpO2 o Temperature * ECG o Heart Rate (HR) (bpm), PR, QRS, QT, QTcF. * Continuous cardiac Holter monitoring (From 30 min before dosing to the end of study drug administration) o Minimum heart rate o Maximum heart rate o Mean Heart rate o Number of single supraventricular ectopy o Number of couplets supraventricular ectopy o Number of single ventricular ectopy o Number of couplets ventricular ectopy o Longest RR pauses o Number of RRs > 2.0 sec * Urine production (L/24h) * Angiotensin 2 in plasma (pg/mL) | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic endpoints (plasma and urine) Pharmacodynamic endpoints Part 1 PainCart Analogue Scale (VAS) pain Curve (AUC), and post-test VAS. Opioid effects * VAS Bond & Lader (Alertness, mood, calmness) * VAS Bowdle (internal perception, external perception, *feeling high*) Pharmacodynamic endpoints Part 2 PainCart * Thermal Pain (Normal Skin): Pain Detection Threshold (PDT). * Electrical pain Stair and Burst (pre-cold pressor): Pain Tolerance Threshold (PTT). * Pressure Pain: Pain Tolerance Threshold (PTT). * Cold Pressor: Pain Tolerance Threshold (PTT). * UVB model Thermal pain (Normal skin): Pain Detection Threshold (PDT) * UVB model Thermal pain (Eerythema skin): Pain Detection Threshold (PDT) NeuroCart * Saccadic eye movement * Smooth pursuit eye movement * Adaptive tracking * Body sway * N-Back * Pharmaco-EEG: power (resting eyes closed, eyes open condition) Opioid effects * Pupillometry (Pupil- and cornea diameter left/right eye) * VAS Bond & Lader (Alertness, mood, calmness) * VAS Bowdle (internal perception, external perception, *feeling high*) * 49-item Addiction Center Research Inventory (ARCI) * Bowel Function Index [BFI] (Baseline *In last 7 days* and Adapted to *Since start of treatment*) Enzyme activity * Aminopeptidase N (APN) (plasma) * Big Endothelin-1 (Big-ET-1) (plasma) | — |
Countries
Netherlands
Outcome results
None listed