Impact of Two Genetic Variants of OATP1B3 or MRP2 or Rifampin on Systemic Disposition and Biological Efficacy of CCK-8

University Medicine Greifswald

Status and phase

Completed

Phase 1

Conditions

Gastrointestinal Hormones

Treatments

Drug: Rifampin

Dietary Supplement: mixed meal

Study type

Interventional

Funder types

Other

Identifiers

NCT02507167

CCK8/RIFA-2012

Details and patient eligibility

About

The purpose of this study is to evaluate the impact of genetic variants of OATP 1B3 or MRP 2 on the systemic disposition of endogenously formed CCK-8 and to determine the influence of a single-dose of the transporter inhibitor rifampin (600 mg) on the systemic disposition of endogenously formed CCK-8. Endogenous CCK-8 secretion will be induced by a single-dose standardized liquid mixed meal.

Enrollment

19 patients

Sex

Male

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

age: 18-45 years
sex: male
12 subjects being homozygote wild-type carriers of OATP 1B3 (c.SLCO 1B3 699 AA and c.SLCO 1B3 334 GG) and MRP 2
12 subjects being homozygotes of the MRP 2 variants (genetic loss of function) and homozygote wild-type carriers of OATP 1B3
12 subjects being homozygotes of the OATP 1B3 variants (c.SLCO 1B3 699 GG and c.SLCO 1B3 334 TT) and homozygotes wild-type carriers of MRP 2
BMI: ≥ 19 kg/m2 and ≤ 27 kg/m2
good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which will be judged by the clinical investigator not to differ in a clinical relevant way from the healthy state
written informed consent given by the volunteer after being provided with detailed information (both, verbally and written) about the nature, risks, and scope of the clinical trial as well as the expected desirable and adverse effects of the drug

Exclusion criteria

hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication
gastrointestinal diseases and/or pathological findings (e.g. stenoses), which might interfere with pharmacokinetics and pharmacodynamics of the study medication
subjects with existing dysfunction in regulation of glucose metabolism, e.g. deficiency of glucose-6-phosphate dehydrogenase (Glc-6-P DHG) and/ or pathological findings
subjects with alcohol and/ or drug dependence and a alcohol consumption more than 20 g alcohol/ day
excessive smoking (more than 10 cigarettes or equivalents/ day)
subjects with positive finding of HBsAG, HIV and/ or drugs
subjects being on a diet (inclusive special or uniform nutritional habits, e.g. vegetarians or undercaloric diet)
strong coffee and/ or tea consumption (≥ 1 liter a day)
subjects suspected or known not to follow instructions
subjects who are unable to understand 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 blackout
subjects who took part in other clinical trials in the last 3 months (blocking time due to another clinical trial with investigational products)
acute illness less than 14 d in the past
blood donation within the last 3 months
any medication within 4 weeks prior to the intended first administration of the study medication which might influence functions of the gastrointestinal tract (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists, proton pump inhibitors, anticholinergics)
any other medication within 2 weeks prior to the first administration of the study medication or less than 10-time the half-live of the respective drug
intake of grapefruit containing food or beverages and poppy seeds containing products 14 d prior to the first drug administration until the last blood sampling of the study