A randomized, double-blind, double dummy, placebo-controlled, four-way cross-over study to investigate the analgesic effects and CNS effects of morphine and pregabalin in healthy subjects

Completed

• Conditions: Chronic Pain

• Registration Number: NL-OMON51629
• Lead Sponsor: Centre for Human Drug Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

1. Healthy subjects, 18 to 65 years of age, inclusive. Healthy status is
defined by absence of evidence of any active or chronic disease following a
detailed medical and surgical history, a complete physical examination
including vital signs, 12-lead ECG, haematology, blood chemistry, and
urinalysis.
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum
weight of 50 kg and a maximum weight of 100 kg.
3. Able to participate and willing to give written informed consent and to
comply with the study restrictions.

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) and 12-lead electrocardiogram (ECG)). Minor deviations 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 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. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus antibody (HIV Ab) at screening.
4. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and
diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg at
screening.
5. Abnormal findings in the resting ECG at screening defined as:
a. QTcF> 450 or < 300 msec for men and QTcF> 470 or < 300 msec for women
b. Notable resting bradycardia (HR < 45 bpm) or tachycardia (HR > 100 bpm)
c. Personal or family history of congenital long QT syndrome or sudden death;
d. ECG with QRS and/or T wave judged to be unfavourable for a consistently
accurate QT measurement (e.g., neuromuscular artefact that cannot be readily
eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T-
and U-waves, prominent U waves);
e. Evidence of atrial fibrillation, atrial flutter, complete branch block,
Wolf-Parkinson-White Syndrome, or cardiac pacemaker
6. 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). Exceptions are paracetamol (up to 4 g/day) and ibuprofen (up to
1g/day), which are allowed up to 2 days before screening and 2 days before each
study drug administration. Other exceptions will only be made if the rationale
is clearly documented by the investigator.
7. 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.
8. Participation in an investigational drug or device study (last dosing of
previous study was within 90 days prior to first dosing of this study).
9. History of abuse of addictive substances (alcohol, illegal substances) or
current use of more than 21 units (for males) or 14 units (for females) of
alcohol per week, drug abuse, or regular user of sedatives, hypnotics,
tranquillisers, or any other addictive agent
10. Positive test for drugs of abuse at screening or pre-dose.
11. Alcohol will not be allowed from at least 24 hours before screening or each
admission.
12. Current use of tobacco or nicotine products and unable to abstain from use
of these products within the previous 3 months before the f

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• Pressure Pain: Pain Detection Threshold (PDT), Pain Tolerance Threshold<br /><br>(PTT), Area Under the Curve (AUC), post-test Visual Analogue Scale (VAS)<br /><br>• • Heat pain (pre-cold pressor: unexposed/normal and UVB-exposed skin, the<br /><br>latter only for subjects with MED lower than 355 mJ/cm2 at screening): PDT, and<br /><br>post-test VAS<br /><br>• Cold Pressor: PDT, PTT, Area Above the Curve (AAC), post-test VAS<br /><br>• Electrical Stair test: PDT, PTT, AUC, post-test VAS<br /><br>• Electrical burst test: PDT, PTT, AUC, post-test VAS<br /><br>• Conditioned Pain Modulation (CPM) Response (change from heat pain pre- and<br /><br>post-cold pressor): PDT<br /><br>• Short Form McGill Pain Questionnaire (SFMPQ) for pressure pain, heat<br /><br>pain, cold pressor, electrical stair test and electrical burst test.</p><br>