NCT02507167

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2012

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2012

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2013

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

July 22, 2015

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 23, 2015

Completed
Last Updated

July 23, 2015

Status Verified

July 1, 2015

Enrollment Period

8 months

First QC Date

July 22, 2015

Last Update Submit

July 22, 2015

Conditions

Gastrointestinal Hormones

Outcome Measures

Primary Outcomes (1)

  • CCK-8

    Cholecystokinin amino acid 8 concentration in blood plasma

    3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal

Secondary Outcomes (7)

  • GLP-1

    3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal

  • GIP

    3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal

  • glucagon

    3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal

  • glucose

    3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal

  • potassium

    3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal

  • +2 more secondary outcomes

Other Outcomes (5)

  • area under the curve AUC from zero to the last sampling time above the limit of quantitation (AUC0-t) of rifampin and DAc-RIF (25-O-desacetyl-rifampin)

    3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2, 3, 4, 6, 8, 10 and 14 h after mixed meal

  • area under the curve AUC from zero to 4 h (AUC0-4h) of rifampin and DAc-RIF (25-O-desacetyl-rifampin)

    3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2 h after mixed meal

  • maximal concentration (Cmax) of rifampin and DAc-RIF (25-O-desacetyl-rifampin)

    3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2, 3, 4, 6, 8, 10 and 14 h after mixed meal

  • +2 more other outcomes

Study Arms (2)

mixed meal

PLACEBO COMPARATOR
Dietary Supplement: mixed meal

mixed meal 2 h after single dose rifampin (600 mg)

ACTIVE COMPARATOR
Dietary Supplement: mixed mealDrug: Rifampin

Interventions

mixed mealDIETARY_SUPPLEMENT

250 ml Fortimel compact (chocolate)

mixed mealmixed meal 2 h after single dose rifampin (600 mg)
RifampinDRUG

oral rifampin administration (600 mg EREMFAT®)

mixed meal 2 h after single dose rifampin (600 mg)

Eligibility Criteria

Age18 Years - 45 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • age: 18-45 years
  • sex: male
  • subjects being homozygote wild-type carriers of OATP 1B3 (c.SLCO 1B3 699 AA and c.SLCO 1B3 334 GG) and MRP 2
  • subjects being homozygotes of the MRP 2 variants (genetic loss of function) and homozygote wild-type carriers of OATP 1B3
  • 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

You may not qualify if:

  • 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)
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Clinical Pharmacology

Greifswald, 17489, Germany

Location

MeSH Terms

Interventions

Rifampin

Intervention Hierarchy (Ancestors)

RifamycinsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic Compounds

Study Officials

  • Werner Siegmund, Prof

    Department of Clinical Pharmacology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 22, 2015

First Posted

July 23, 2015

Study Start

November 1, 2012

Primary Completion

July 1, 2013

Study Completion

December 1, 2014

Last Updated

July 23, 2015

Record last verified: 2015-07

Locations

DE(1)