Drug Release and Absorption from Controlled Release Formulations in Patients with Gastrointestinal Dysfunctions.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2017-000732-34-DK
• Date of registration: 25/04/2017
• Prospective Registration: Yes
• Primary sponsor: Mech-Sense, Dept. Gastroenterology & Hepatology, Aalborg University Hospital
• Public title: Drug Release and Absorption from Controlled Release Formulations in Patients with Gastrointestinal Dysfunctions.
• Scientific title: Oral Controlled Release Formulations to Patients with Gastrointestinal Dysfunction – Is the Release of Drug and the Absorption Impaired? - ABOXY
• Date of first enrolment: 21/06/2017
• Target sample size: 135
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000732-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: yes; Other: yes; Other trial design description: Semi-double blinded (no placebo but participants are unknown to the effects of the drug formulations; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Denmark

Contacts

• Name: Louise Ladebo Rasmussen
• Affiliation: Mech-Sense, Dept. Gastroenterology & Hepatology, Aalborg University Hospital

• Name: Louise Ladebo Rasmussen
• Affiliation: Mech-Sense, Dept. Gastroenterology & Hepatology, Aalborg University Hospital

Key inclusion & exclusion criteria

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


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Healthy (pain) and patients (pain).
MedDRA version: 20.1 Level: LLT Classification code 10009093 Term: Chronic pancreatitis System Organ Class: 100000004856
MedDRA version: 20.0 Level: LLT Classification code 10012594 Term: Diabetes System Organ Class: 100000004861
MedDRA version: 20.0 Level: LLT Classification code 10048516 Term: Gastrointestinal disorder (NOS) System Organ Class: 100000004856
MedDRA version: 20.0 Level: LLT Classification code 10050554 Term: Gastric bypass NOS System Organ Class: 100000004865

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Oxynorm
Product Name: Oxynorm
Pharmaceutical Form: Oral solution
INN or Proposed INN: Oxycodone
CAS Number: 124-90-3
Other descriptive name: OXYCODONE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Oxycodonhydrochlorid ”Lannacher”, depot tablets
Product Name: Oxycodonhydrochlorid ”Lannacher”, depot tablets
Pharmaceutical Form: Modified-release tablet
INN or Proposed INN: Oxycodone
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Oxycodone Depot ”Sandoz”, depot tablets
Product Name: Oxycodone Depot ”Sandoz”, depot tablets
Pharmaceutical Form: Modified-release tablet
INN or Proposed INN: Oxycodone
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

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.

Main Objective: 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.

Secondary Objective: 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.

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).

Secondary Outcome(s)

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.

Secondary end point(s): Pharmadynamics parameters defined as
o Change in pupil size when given oxycodone.
o Pain response to muscle pressure.

Secondary ID(s)

ABOXY_2017

Source(s) of Monetary Support

Mech-Sense, Aalborg University Hospital

Aalborg University

Ethics review

Status: Approved
Approval date:
Contact: