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

NCT03012763 | Completed Phase 1

• 1 other identifier: GIT-Physiol_2016
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pharmacokinetics; Magnetic Resonance Imaging; Administration, Oral

Outcome Measures

Primary Outcomes (4)

• area under the concentration time curve (AUC)

  Computed with the measured concentration of Paracetamol, Fexofenadine and Valsartan in blood samples.

  up to 51 h after drug administration

• area under the curve of small bowel water volume

  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.

  up to 6.75 h after drug administration

• gastric emptying rate

  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.

  up to 6.75 h after drug administration

• lag-Time of sulfapyridine (orocecal transit times)

  Estimated as the first significant concentration (\>50 or 100 ng/ml) of sulfapyridine in blood samples after administration of Sulfasalazine.

  up to 51 h after drug administration

Study Arms (3)

non-caloric water

PLACEBO COMPARATOR

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; Drug: Sulfasalazine; Drug: Fexofenadine; Drug: Valsartan; Device: non-caloric water

caloric drink

ACTIVE COMPARATOR

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; Drug: Sulfasalazine; Drug: Fexofenadine; Drug: Valsartan; Device: caloric drink

grapefruit juice

ACTIVE COMPARATOR

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; Drug: Sulfasalazine; Drug: Fexofenadine; Drug: Valsartan; Device: grapefruit juice

Interventions

Paracetamol DRUG

Oral administration of 250 mg paracetamol

caloric drink; grapefruit juice; non-caloric water

Sulfasalazine DRUG

Oral administration of 50 mg sulfasalazine

caloric drink; grapefruit juice; non-caloric water

Fexofenadine DRUG

Oral administration of 120 mg fexofenadine

caloric drink; grapefruit juice; non-caloric water

Valsartan DRUG

Oral administration of 40 mg valsartan

caloric drink; grapefruit juice; non-caloric water

non-caloric water DEVICE

Oral administration of 240 ml non-caloric water

non-caloric water

caloric drink DEVICE

Oral administration of 240 ml caloric drink

caloric drink

grapefruit juice DEVICE

Oral administration of 240 ml grapefruit juice

grapefruit juice

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medicine Greifswald: lead

MeSH Terms

Interventions

Acetaminophen; Sulfasalazine; fexofenadine; Valsartan

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfonamides; Sulfones; Sulfur Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2017
• First Posted: January 6, 2017
• Study Start: April 1, 2016
• Primary Completion: January 1, 2017
• Last Updated: January 6, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share