E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy (pain) and patients (pain). |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009093 |
E.1.2 | Term | Chronic pancreatitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012594 |
E.1.2 | Term | Diabetes |
E.1.2 | System Organ Class | 100000004861 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048516 |
E.1.2 | Term | Gastrointestinal disorder (NOS) |
E.1.2 | System Organ Class | 100000004856 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050554 |
E.1.2 | Term | Gastric bypass NOS |
E.1.2 | System Organ Class | 100000004865 |
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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 |
The main objective of this study is to investigate the impact of GI-pathophysiology on net absorption of oxycodone administered as immediate release formulations and two different types of CRFs in patients with gastrointestinal disorders and to compare results obtained in healthy volunteers. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to investigate if the pharmacodynamic effect of oxycodone is different depending on the formulation both within patients groups and when compared to healthy volunteers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
General inclusion criteria: • Signed informed consent. • Able to read and understand Danish. • Northern European descent (in order to minimize genetic variance influences on pain perception and drug metabolism). • The researcher believes that the participant understands the study details, is compliant and is expected to complete the study. • 25-80 years of age • The investigator will ensure that fertile female participants use a safe contraception method during the study and for at least 32,5 hours after termination of the last treatment visit. The following methods are considered as safe contraception methods: the pill, spiral, injection of controlled release progestogen, subdermal implantation, hormonal vaginal ring or transdermal patches. • The investigator will ensure that fertile female participants have a negativ pregnancy test before each treatment visit.
Specific inclusion criteria for healthy volunteers • Opioid naïve* • BMI between 18,5-29,9 kg/m2 • eGFR, ALAT, bilirubin, hemglobin and HbA1c levels are all normal or non-clinical significant (Assessed by a medical doctor) • Healthy (Assessed by a medical doctor)
Specific inclusion criteria for the diabetic patients • Diagnosed with diabetes mellitus • GI symptoms (eg. nausea, abdominal pain) • Oxycodone naïve (has not taken oxycodone for at least 1 week)
Specific inclusion criteria for the chronic pancreatitis patients • Diagnosed with chronic pancreatitis and exocrine insufficiency (f-elastase below 100 μg/g stool) • Oxycodone naïve (has not taken oxycodone for at least 1 week)
Specific inclusion criteria for the gastric bypass patients • Have undergone a gastric bypass surgery at least one year ago or longer • Oxycodone naïve (has not taken oxycodone for at least 1 week)
Specific inclusion criteria for the short bowel patients • Has a stoma • Resection occurred at least one year ago or longer • Has at least 150 cm small intestine • Oxycodone naïve (has not taken oxycodone for at least 1 week)
Specific inclusion criteria for the short bowel patients (pilot study) • Has a stoma • Has less than 150 cm small intestine • Has not taken oxycodone for at least 48 hours
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E.4 | Principal exclusion criteria |
General exclusion criteria for all participants • Known hypersensitivity or allergy towards the pharmaceutical compounds used in the study or pharmaceutical compounds similar to those used in the study • Participation in other intervention studies within 14 days prior to first visit • Expected need of new medication or surgical treatment during the course of the study • Any diagnosed disease, which investigator concludes will affect the trial • Daily alcohol consumption • Intake of alcohol 48 hours prior or during the study days • Consumption of grapefruit juice or juice from Seville oranges (strong CYP3A4 inhibitors) 48 hours prior or during the study days • (Daily) use of any prescription, non-prescription and/or herbal medicines that may influence the study results (eg. strong inhibitors or inducers of CYP3A4, oxycodone) • Any contraindications related to the investigational drugs (severe respiratory depression, severe heart disease, chronic obstructive pulmonary disease or acute severe asthma and paralytic ileus) • Female participants who are lactating • Intake of non-opioids 24 hours prior or during the study days • Known allergy towards any of the Smartbar content
Specifik exclusion criteria for healthy volunteers • Has persistent pain. • Daily nicotine comsumption (e.g. cigarette smoking, nicotine patch etc.) • History of substance abuse • Family history of substance abuse
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are the pharmacokinetic parameters defined as Cmax (maximum plasma concentration), Tmax (time at maximum plasma concentration), F (bioavailabilty), ka (rate of absorption) and AUC (area under the plasma concentration curve). These values are all derived from the blood concentrations of oxycodone. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Eighteen blood samples (9 mL each) will be taken at specified times over a periode of 12 hours. One before drug administration and the rest after. A final blood sample will be taken the next morning (approx. 24 hours after drug administration). |
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E.5.2 | Secondary end point(s) |
Pharmadynamics parameters defined as o Change in pupil size when given oxycodone. o Pain response to muscle pressure.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pupil eye diameter will be recorded 19 times during the day. One time before drug administration and the rest afterwards. Muscle pressure will be applied 9 times during the day. One before drug administration and the rest afterwards. |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 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 | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Semi-double blinded (no placebo but participants are unknown to the effects of the drug formulations |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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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LVLS (last visit of the last participant) |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |