E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients undergoing elective major abdominal surgery |
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E.1.1.1 | Medical condition in easily understood language |
Patients undergoing elective major abdominal surgery |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054799 |
E.1.2 | Term | Perioperative analgesia |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054711 |
E.1.2 | Term | Postoperative pain |
E.1.2 | System Organ Class | 100000004863 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the analgesic efficacy of perioperative Namisol® for postoperative pain in the first 5 days after abdominal surgery. Analgesic efficacy is measured as the difference in visual analog scale (VAS) area under the curve (AUC) for the first 5 postoperative days between placebo and Namisol®. |
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E.2.2 | Secondary objectives of the trial |
To investigate the analgesic efficacy of Namisol for persistent postoperative pain after major abdominal surgery.
To investigate the effect of Namisol on total consumption of analgesics the first 5 postoperative days.
To investigate the effect of Namisol on total consumption of analgesics for the first 24 postoperative weeks.
To investigate the effect of Namisol on the incidence and severity of postoperative nausea/vomiting
To investigate the effect of Namisol on sedation level
To investigate the effect of Namisol on central nervous system processing, and sensitization
To evaluate the effect of Namisol on anxiety and depression, general health, pain catastrophizing, global impression of change, pain related anxiety , postoperative recovery, treatment satisfaction, and appetite
To evaluate the effect of Namisol on safety and tolerability
To evaluate the effect of Namisol on pharmacodynamics
To evaluate the effects of Namisol on perioperative cytokine levels |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is between 18 and on the day the informed consent form will be signed.
2. Patient has persistent or intermittent abdominal pain, due to underlying pathology including diverticulitis, m. Crohn, ulcerative colitis, endometriosis, or abdominal adhesions. Other pathology may be included if so judged by the investigator.
3. Patient is undergoing elective, open abdominal surgery with planned use of an epidural catheter the surgical procedure has an estimated duration of at least two hours, not including the time to induce anesthesia.
4. Patient scores I to III in the American Society of Anesthesiologists physical status classification system (ASA I-III).
5. Patient has a stable medication regimen of analgesics for at least 2 weeks prior to study entry.
6. Patient is willing and able to comply with the lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other trial procedures.
7. Patient is able to speak, read and understand the local language of the investigational site, is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent prior to screening evaluations.
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E.4 | Principal exclusion criteria |
1. Patient is diagnosed with chronic pancreatitis, ACNES, abdominal hernia, inguinal hernia, abdominal wall pathology or intestinal fistula.
2. Patient suffers from persistent or intermittent abdominal pain (on a daily basis in at least 3 months) with average NRS ≥ 3, based or probably based on past abdominal surgery or other causes for the pain, for example, continuing malignancy, chronic infection or from diabetes mellitus.
3. Patient has an unstable regimen of analgesics or a regimen of analgesics which includes tricyclic antidepressants or 2--binding Ca++ channel blockers such as gabapentin.
4. Patient is ineligible for the anesthesia protocol, as judged by the investigator.
5. Patient is admitted to the hospital on the day of surgery itself
6. Patient used any cannabinoids (by smoking cannabis or oral intake) for at least one month on the day of screening.
7. Patient has a (history of) a malignant or other significant medical disorder that, in the opinion of the investigator, may interfere with the study or may pose a risk for the patient, including terminal illness.
8. Patient uses concomitant medication that, in the opinion of the investigator, may interfere with the study or may pose a risk for the patient (e.g. HIV antivirals).
9. Patient does not tolerate oral intake of food/liquids or is refrained from oral intake because of medical reasons.
10. Patient demonstrates clinical relevant deviations in the electrocardiogram (ECG) parameters at screening.
11. Patient is at the moment of screening diagnosed with moderate to severe renal impairment as judged by the investigator.
12. Patient is at the moment of screening diagnosed with moderate to severe hepatic failure as judged by the investigator.
13. Patient has a presence or history of major psychiatric illness as judged by the investigator, e.g. major depression, schizophrenia.
14. Patient demonstrates clinically significant laboratory abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
15. Patient has a known history of alcohol or substance abuse.
16. Patient has a history of sensitivity / idiosyncrasy to THC, compounds chemically related to these compounds, or to any other related drug used in the past.
17. Patient demonstrates a positive urine drug screen at screening visit for THC, cocaine, MDMA, and amphetamines.
18. Female patient is pregnant (childbearing potential must have a negative pregnancy test prior to each study day) or breastfeeding during the course of the study.
19. Female childbearing potential has to use acceptable birth control measures including oral contraceptives, intrauterine devices or mechanical methods.
20. Patient intends to conceive a child during the course of the study.
21. Patient participates in another investigational drug study within 90 days prior to the first dose and/or participates in more than 2 clinical trials in the last year.
22. Patient has a clinical significant exacerbation in illness within two weeks of participating in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
o Short-term postoperative pain intensity
Daily VAS average pain |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Repeatedly, from five days before surgery (-5, baseline) up to +6 postoperative months |
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E.5.2 | Secondary end point(s) |
o Long-term postoperative pain intensity
Weekly pain diary
o Short-term postoperative consumption of analgesics
Number of PCA requests and deliveries
Total dose of escape medication
o Long-term postoperative consumption of analgesics
Post-discharge use of analgesics
o Central nerve system processing and sensitization
QST (focal and peripheral)
• Pressure pain thresholds
• Electric pain thresholds
• Electric wind-up response
Conditioned Pain Modulation (CPM)
Sensitization
• Peri-incisional Von Frey filament testing
• Peri-incisional brush stroke testing
o Questionnaires
VAS Bond & Lader
VAS Bowdle
HADS
SF-36
PCS
PGIC
PASS
QoR-40
AppLe
TSQM v. II
o Postoperative sedation level
Ramsay sedation score
o Postoperative nausea and vomiting (PONV)
Incidence of nausea and vomiting
Rescue medication
o Immune system response
TNF-
Interleukins IL-1, IL-6 and IL-10
Matrix metalloproteases MMP-2 and MMP-9
o Pharmacogenetics
o Safety
Laboratory
ECG
HF and BP
Adverse events, including postoperative nausea/vomiting
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Repeatedly, from twenty days before surgery (-20, baseline) up to +6 postoperative months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |