A randomised, double-blind, placebo-controlled, dose-ranging partial-block crossover study to investigate the effect of intravenous oliceridine on CNS functioning and nociceptive thresholds in healthy subjects, compared to morphine.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

Subjects must meet all the following criteria to be included in this study:
1. Signed informed consent prior to any study-mandated procedure.
2. Ability to communicate well with the Investigator in the Dutch language and
willing and able to follow the procedures and comply with study restrictions as
outlined in the protocol.
3. Healthy male and female volunteers aged *18 years and *55 years old at the
time of informed consent.
4. Body mass index (BMI) *18 and <32 kg/m2 at Screening.
5. Females of childbearing potential must agree to the use of the
double-barrier contraceptive method, meaning the use of a highly effective
method of contraception (e.g., intrauterine device (IUD), diaphragm with
spermicide, oral contraceptive, injectable progesterone, subdermal implant or a
tubal ligation) in combination with the use of a condom by a male partner of
the female subject, from screening through 5 half-lives or 90 days, whichever
is longer, after administration of the last dose of IP.
6. Males who are sexually active and whose partners are females of childbearing
potential must agree to use condoms from screening through 5 half-lives or 90
days, whichever is longer, after administration of the last dose of IP, and
their partners must be willing to use a highly effective method of
contraception (e.g., IUD, diaphragm with spermicide, oral contraceptive,
injectable progesterone, subdermal implant or a tubal ligation) from screening
through 5 half-lives or 90 days after administration of the last dose of IP.

Exclusion Criteria

1. Poor metabolisers of CYP 2D6 substrates, as defined after genotyping
assessment at screening.
2. 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 until follow up.
3. Any current, clinically significant, known medical condition that would
affect sensitivity to cold (such as atherosclerosis, Raynaud*s disease,
urticaria, hypothyroidism) or pain (including pain disorders, such as chronic
low back pain and osteoarthritis, or diseases or conditions that cause pain,
hypaesthesia, hyperalgesia, allodynia, paraesthesia, neuropathy, etc.), in the
opinion of the investigator.
4. Subjects indicating pain test intolerability at Screening or achieving pain
tolerance at >80% of maximum input intensity for the cold pressor pain test.
5. Clinically significant illness or disease (e.g., psychiatric disorders,
disorders of the gastrointestinal tract, liver [excluding Gilbert*s syndrome],
kidney [including nephrectomy], respiratory system, endocrine system,
haematological system, neurological system, or cardiovascular system,
dermatologic condition, clinically significant infection within 2 weeks of
dosing, or subjects who have a congenital abnormality in metabolism), or any
clinically significant abnormal symptom or organ impairment, as judged by the
Investigator, found by medical history, physical examinations, vital signs,
electrocardiogram (ECG) finding, or either abnormal laboratory values or
laboratory test results at Screening or Baseline.
6. Any finding that may compromise the safety of the subject or affect their
ability to adhere to the protocol requirements (e.g., difficulty with venous
access or fear of needles).
7. Presence of any condition in which an opioid is contraindicated (e.g.,
opioid intolerance, significant respiratory depression, acute or severe
bronchial asthma, gastrointestinal ileus, etc.).
8. A prolonged corrected QT interval (Fridericia-corrected QT interval [QTcF]
>450 ms in males and >470 in females) demonstrated on ECG at Screening or
Baseline.
9. A history of risk factors for torsade de pointes (e.g., heart failure,
hypokalaemia, family history of long QT syndrome). A history of myocardial
infarction, ischaemic heart disease, or cardiac failure at Screening. History
of clinically significant arrhythmia or uncontrolled arrhythmia as determined
by the Investigator at Screening.
10. Left bundle branch block at Screening or Baseline.
11. Systolic blood pressure (BP) >140 or <90 mmHg or diastolic BP >90 or <50
mmHg at Screening or Baseline, or history of clinically significant orthostatic
hypotension.
12. Heart rate (HR) <45 beats per minute (bpm) or >100 bpm at Screening or
Baseline.
13. Demonstrated allergic reactions (e.g., food, drug, atopic reactions, or
asthmatic episodes) which, in the opinion of the Investigator, interfere with
the subject*s ability to participate in the trial.
14. Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibodies
(Anti-HBc), hepatitis C antibodies (HCV Ab), or human immunodeficiency virus
antibody (HIV Ab) at Screening.
15. Use of nicotine-containing products within 4 weeks before the Screening
visit and not able to withhold from smoking during the study.
16. History o