E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
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 study the pharmacokinetics of acetaminophen and metabolites in morbidly obese patients and compare with normal weight patients. |
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E.2.2 | Secondary objectives of the trial |
- To compare the pharmacokinetics of acetaminophen and metabolites in morbidly obese patients at the time of bariatric surgery and 0.5 – 2 year after bariatric surgery. - To compare the safety of acetaminophen in morbidly obese patients with normal weight patients. - Assess the influence of both demographic (age, sex) and physiologic covariates (body weight, insulin resistance, lipid levels and inflammation markers) on acetaminophen pharmacokinetics. - To evaluate the metabolomic profile in morbidly obese patients and normal weight patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for morbidly obese patients: - BMI > 40 kg/m2 undergoing bariatric surgery. - 18 -60 years old - ASA physical classification of II or III - All racial and ethnic groups will be included
Inclusion criteria for normal weight patients: - BMI between 18 and 25 kg/m2 undergoing general surgery - 18 -60 years old - ASA physical classification of I, II or III - All racial and ethnic groups will be included
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E.4 | Principal exclusion criteria |
Exclusion criteria for all patient groups: - Renal insufficiency identified by GFR < 60 ml/min/1.73m2 - Liver disease identified by liver function tests: ASAT, ALAT, prothrombin time, γ-GT, bilirubin, creatinine, albumin and alkaline phosphatase (ALP) ( > 3 times upper limit of normal values) - Patients with Gilbert-Meulendracht syndrome - Chronic alcohol intake or use of alcohol within last 72 hours - Pregnancy or breastfeeding - Patients who are treated with drugs know to affect CYP2E1 and UGT (UDP-glucuronyltransferases) - Diabetes mellitus type II patients - Smoking - Acetaminophen intake before the study (24 hours before study)
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E.5 End points |
E.5.1 | Primary end point(s) |
Clearance (total, glucuronidation, sulphation, CYP2E1 oxidation and unchanged) and volume of distribution of acetaminophen in morbidly obese patients in comparison with normal weight patients. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Around bariatric surgery for the morbidly obese patients and around general surgery for the normal weight patients. |
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E.5.2 | Secondary end point(s) |
- Difference in clearance (total, glucuronidation, sulphation, CYP2E1 oxidation) and volume of distribution of acetaminophen in morbidly obese patients at the time of bariatric surgery and at 0.5 – 2 year after bariatric surgery. - Liver function tests (ASAT, ALAT, prothrombin time, gamma- GT, bilirubin, creatinine and albumin) in morbidly obese patients in comparison with normal weight patients.
Other endpoints that will be measured: - Total body weight, length and fat (free) mass - Insulin resistance: homa IR (fasting insulin and glucose levels) - Lipid levels: free fatty acids, triglycerides, cholesterol - Inflammation markers: TNF-alfa, IL-6, leptin, adiponectin and CRP - Metabolomic profile
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the time of bariatric surgery and 0.5-2 years after bariatric surgery At the time of general surgery for the normal weight patients. |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
patient with normal weight |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |