Oral Pharmacokinetics of Sulfasalazine, Paracetamol, Fexofenadine and Valsartan Using Different Administration Mediums

Sponsor

University Medicine Greifswald (Other)

Overall Status

Completed

CT.gov ID

NCT03012763

Collaborator

(none)

Enrollment

Arms

Study Details

Study Description

Brief Summary

The purpose of this study is to determine pharmacokinetics of the probe-drugs sulfasalazine, given in 240 ml non-caloric water and paracetamol, fexofenadine and valsartan after oral administration, given in 240 ml non-caloric water, in 240 ml caloric drink or in 240 ml grapefruit juice prior to ingestion and to visualize the localization and to measure the filling volume of stomach, small intestine as well as ascending, transverse and descending colon by T2-weighted magnetic resonance imaging after oral administration of 240 ml water (non-caloric water), after administration of 240 ml caloric drink and after administration of 240 ml grapefruit juice.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics Magnetic Resonance Imaging Administration, Oral	Drug: Paracetamol Drug: Sulfasalazine Drug: Fexofenadine Drug: Valsartan Device: non-caloric water Device: caloric drink Device: grapefruit juice	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Pharmacokinetics of Sulfasalazine, Paracetamol, Fexofenadine and Valsartan After Oral Administration Using 240 ml Non-caloric Water, a Carbohydrate Enriched Drink and Grapefruit Juice in Correlation to the Intestinal Availability of Water as Quantified by MRI-based Volumetry in 9 Healthy Male and Female Subjects

Study Start Date :

Apr 1, 2016

Actual Primary Completion Date :

Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: non-caloric water 50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml non-caloric water 3 h thereafter	Drug: Paracetamol Oral administration of 250 mg paracetamol Drug: Sulfasalazine Oral administration of 50 mg sulfasalazine Drug: Fexofenadine Oral administration of 120 mg fexofenadine Drug: Valsartan Oral administration of 40 mg valsartan Device: non-caloric water Oral administration of 240 ml non-caloric water
Active Comparator: caloric drink 50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml caloric drink 3 h thereafter	Drug: Paracetamol Oral administration of 250 mg paracetamol Drug: Sulfasalazine Oral administration of 50 mg sulfasalazine Drug: Fexofenadine Oral administration of 120 mg fexofenadine Drug: Valsartan Oral administration of 40 mg valsartan Device: caloric drink Oral administration of 240 ml caloric drink
Active Comparator: grapefruit juice 50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml grapefruit juice 3 h thereafter	Drug: Paracetamol Oral administration of 250 mg paracetamol Drug: Sulfasalazine Oral administration of 50 mg sulfasalazine Drug: Fexofenadine Oral administration of 120 mg fexofenadine Drug: Valsartan Oral administration of 40 mg valsartan Device: grapefruit juice Oral administration of 240 ml grapefruit juice

Arm

Intervention/Treatment

Placebo Comparator: non-caloric water

50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml non-caloric water 3 h thereafter

Drug: Paracetamol

Oral administration of 250 mg paracetamol

Drug: Sulfasalazine

Oral administration of 50 mg sulfasalazine

Drug: Fexofenadine

Oral administration of 120 mg fexofenadine

Drug: Valsartan

Oral administration of 40 mg valsartan

Device: non-caloric water

Oral administration of 240 ml non-caloric water

Active Comparator: caloric drink

50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml caloric drink 3 h thereafter

Drug: Paracetamol

Oral administration of 250 mg paracetamol

Drug: Sulfasalazine

Oral administration of 50 mg sulfasalazine

Drug: Fexofenadine

Oral administration of 120 mg fexofenadine

Drug: Valsartan

Oral administration of 40 mg valsartan

Device: caloric drink

Oral administration of 240 ml caloric drink

Active Comparator: grapefruit juice

50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml grapefruit juice 3 h thereafter

Drug: Paracetamol

Oral administration of 250 mg paracetamol

Drug: Sulfasalazine

Oral administration of 50 mg sulfasalazine

Drug: Fexofenadine

Oral administration of 120 mg fexofenadine

Drug: Valsartan

Oral administration of 40 mg valsartan

Device: grapefruit juice

Oral administration of 240 ml grapefruit juice

Outcome Measures

Primary Outcome Measures

area under the concentration time curve (AUC) [up to 51 h after drug administration]
Computed with the measured concentration of Paracetamol, Fexofenadine and Valsartan in blood samples.
area under the curve of small bowel water volume [up to 6.75 h after drug administration]
Dynamic enhanced magnetic resonance examination gradient-echo T2-weighted HASTE images (TR 1300 ms, TR 321 ms, flip-angle 160°) will be acquired on a 1.5 Tesla MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging. The obtained MRI files will be investigated with common radiological software (OsiriX, Voxar 3D, Fiji, 3D slicer). From the DICOM files there will obtained: Gastrointestinal volumes and their kinetics for stomach, small bowel, colon segments and gallbladder.
gastric emptying rate [up to 6.75 h after drug administration]
Dynamic enhanced magnetic resonance examination gradient-echo T2-weighted HASTE images (TR 1300 ms, TR 321 ms, flip-angle 160°) will be acquired on a 1.5 Tesla MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging. The obtained MRI files will be investigated with common radiological software (OsiriX, Voxar 3D, Fiji, 3D slicer). From the DICOM files there will obtained: Gastrointestinal volumes and their kinetics for stomach, small bowel, colon segments and gallbladder. Gastric emptying rate will be estimated as the half life of water volumen in the stomach.
lag-Time of sulfapyridine (orocecal transit times) [up to 51 h after drug administration]
Estimated as the first significant concentration (>50 or 100 ng/ml) of sulfapyridine in blood samples after administration of Sulfasalazine.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

ethnic origin: Caucasian
body mass index: ≥ 18.5 kg/m² and ≤ 30 kg/m²
good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
written informed consent

Exclusion Criteria:

weight less than 45 kg
claustrophobia
tinnitus
cardiac pacemakers, metallic, plastic or silicone implants, dental retainer or metal-containing tattoos and piercings, Permanent Make-Ups, intrauterine devices
known allergic reactions/ hypersensitivity to the active ingredients used or to constituents of the study medication (e.g. lactose, lecithin, sulfonamides, salicylates)
bronchial asthma (all stages) and other known allergic diseases
existing cardiac, haematopoietic or hematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability and/or pharmacokinetics or the requirements for the magnetic resonance tomography
known hyperkalemia, hyponatremia or hypovolemia or medications that may cause these conditions.
Hepatic, renal or metabolic diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication (e.g. liver failure, kidney failure, acute intermittent porphyria).
gastrointestinal diseases and/or pathological findings, which might interfere with gastrointestinal motility and emptying processes and interfering with pharmacokinetics and pharmacodynamics of the study medication (e.g. ileus)
Erythema exsudativum multiforme.
Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency).
Acute, chronic or recurrent infections.
drug or alcohol dependence
positive drug or alcohol screening
smokers of 10 or more cigarettes per day
positive results in HIV, hepatitis B virus and hepatitis C virus screenings
subjects who are on a diet which could affect gastrointestinal motility or the pharmacokinetics of the drug (vegetarian, vegan)
eating disorders e.g. anorexia, bulimia
heavy tea or coffee drinkers (more than 1l per day)
lactation and/or pregnancy test positive or not performed
subjects suspected or known not to follow instructions
subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
subjects liable to orthostatic dysregulation, fainting or blackouts
participation in a clinical trial during the last 3 months prior to the planned start of the study less than 3 months after last blood donation
therapy with transdermal patches
any systemically available medication within 2 weeks prior to the intended first administration unless because of the terminal elimination half-life complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)
intake of grapefruit or poppy seeds containing products within 14 days prior to the start of the study
Females who don't fulfil the criteria for contraception as listed in section 7.5.1 of this protocol

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University Medicine Greifswald

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Medicine Greifswald

ClinicalTrials.gov Identifier:

NCT03012763

Other Study ID Numbers:

GIT-Physiol_2016

First Posted:

Jan 6, 2017

Last Update Posted:

Jan 6, 2017

Last Verified:

Jan 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 6, 2017