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A study of the effects of different doses of oliceridine on several brain functions and a pain test, in healthy volunteers, compared to morphine

Phase 1
Completed
Conditions
Effects of oliceridine and morphine on neurocognition and pain in healthy participants
Not Applicable
Registration Number
ISRCTN13308001
Lead Sponsor
Trevena, Inc.
Brief Summary

2023 Results article in https://doi.org/10.1097/ALN.0000000000004758 (added 15/09/2023)

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
All
Target Recruitment
23
Inclusion Criteria

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 investigational product (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 over-the-counter (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 Scre

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
eurocognitive function is measured using the saccadic eye movement's peak velocity (°/s) at pre-dose, 30min, 1, 2 , 3, 4, 5, and 6 h.
Secondary Outcome Measures
NameTimeMethod
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