- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02054299
Open Label Pharmacokinetic-Pharmacogenetic Study on Polymorphisms in the Organic Cation Transporter OCT1 (PG-OCT)
May 11, 2016 updated by: Johannes Matthaei, University Medical Center Goettingen
Effects of Genetic Polymorphisms in the Organic Cation Transporter OCT1 on Cellular Uptake and Metabolism of Antidepressants and Other Organic Cationic Drugs
The purpose of this study is to determine the effect of the organic cation transporter OCT1 polymorphisms on the pharmacokinetics of several drugs in order to explain efficacy and adverse effects.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Goettingen, Germany, 37075
- Department of Clinical Pharmacology, University Medical Center Goettingen
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Written informed consent obtained prior to study entry including informed consent for molecular genetic analysis concerning candidate genes relevant for pharmacokinetics and pharmacodynamics of the study medication.
- Both genders (male and female), as far as feasible, in each of the 3 OCT1 genotype groups, an equal proportion of males and females will be included.
- Healthy adults aged ≥18 to < 50 years
- Body weight not less than 48 kg and body mass index (BMI) not less than 17 kg/m² and not greater than 32 kg/m².
- Willingness to meet the study instructions and to co-operate with the study personal
- No clinically relevant pathological findings in any of the investigations at the screening visit. Minor deviations of laboratory values from the normal range may be accepted, if judged by the investigator to have no clinical relevance
- Systolic blood pressure ≤ 140 mmHg and ≥ 100 mmHg, diastolic blood pressure ≤ 90 mmHg and ≥ 60 mmHg and heart rate ≤ 90 bpm and ≥ 50 bpm at screening visit
- Female subjects will only be included if they express their willingness not to become pregnant during the entire study period by practicing abstinence or reliable methods of contraception as specified in the respective protocol section.
Exclusion Criteria:
- Unwillingness or inability to give informed consent
- Involvement in the planning and conduct of the study (applies to staff directly employed at the study site / department)
- Participation in a clinical study or use of any other investigational or non-registered drug or vaccine during the study period or within 30 days preceding the first dose of study drugs.
- Blood, plasma or thrombocyte donation during the last 15 days prior to application of the test drugs.
- Any planned surgical treatment during the last 14 days prior and 14 days after the application of the test drugs.
- Known pregnancy or lactation period
- Any relevant pathological findings in any of the investigations at the screening visit including significant abnormalities as result of the medical-screening-laboratory-analysis, especially of the liver and kidney related parameters unless judged as medically irrelevant.
- QTcF > 450 ms in screening ECG
- Systolic blood pressure > 140 mmHg and < 100 mmHg, diastolic blood pressure > 90 mmHg and < 60 mmHg and heart rate > 90 bpm and < 50 bpm pre-dose at treatment period 4 (Amitriptyline)
- Any disease affecting liver or kidney or impairment of the liver or kidney-function
- Any cardiovascular disease
- Moderate to severe hypertension requiring medication therapy
- Bronchogenic asthma requiring constant drug treatment (stages 2 to 4 asthma)
- Diabetes mellitus, hyperthyroidism, hypothyroidism
- Glaucoma
- Symptomatic prostatic hyperplasia
- Any medical constellation that increases risk of bleeding, including chronic treatment with NSAID or COX-2 inhibitors
- History of alcohol and/or drug abuse and/or any abusive use of medicaments and/or positive drug screen
- History of any psychiatric or neurologic disorder. If there are any doubts at the screening visit on whether a person is suffering from a depression or not he or she will be excluded from the study or examined by a psychiatrist for clarification before inclusion.
- Any major gastrointestinal disease and any gastrointestinal disorder that is expected to significantly interfere with the pharmacokinetics of the study drug
- Gastrointestinal surgery which may interfere with the pharmacokinetics of the study drug (except appendectomy or herniotomy)
- Taking any medication within 7 days before or during the trial with the following exceptions: Oral contraceptive drug used will be documented but will not be an exclusion criterion. Other medication might be allowed on single case basis if considered necessary for the subject's safety and well-being and if interactions with the study medication are judged as irrelevant.
- Any other findings that could compromise the safety of the participant or the quality of the study-results
- Any known hypersensitivity or allergic reactions to any of the tested drugs
- History of severe hypersensitivity reactions and anaphylaxis
- Any other clinically significant diseases as judged by the investigator
- Body temperature > 37.5°C prior to drug application
- Known infection with HIV, Hepatitis B (HBsAg) or Hepatitis C (no laboratory diagnostics concerning these diseases will be performed within the present study)
- Inability or unwillingness to avoid any intake of alcohol from 48 h prior to until 72 hours after Investigational Medicinal Product (IMP) application application
- Pregnancy (positive pregnancy test performed prior to drug administration)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Drug application
6 treatment periods.
On each period one of the following interventions
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Amitriptyline: 25 mg, single oral application
Desvenlafaxine: 50 mg, single oral application
Sumatriptan: 50 mg, single oral application
Proguanil: 200mg, single oral application
Fenoterol: 180 mcg, single intravenous application
Thiamine: 200mg, single oral application
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area under the plasma concentration-time curve (AUC) of the investigational drugs
Time Frame: up to 60 hours
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up to 60 hours
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Total clearance, Cmax, Tmax, Mean AbsorptionTime, Alpha and Beta half-lives, Mean Residence Time (MRT) and Volume of distribution of the investigated drugs and their metabolites
Time Frame: up to 60 hours
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up to 60 hours
|
Dry mouth, fatigue, nausea, headache, vertigo, tinnitus, chills, anxiety and difficulties to read on Visual Analog Scales.
Time Frame: up to 60 hours
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up to 60 hours
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Sedation on Stanford sedation scale
Time Frame: up to 60 hours
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up to 60 hours
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Pupil diameter, latency, diameter at maximal constriction, amplitude and time for 33% recovery of initial pupil diameter measured by pupillometrie
Time Frame: up to 60 hours
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up to 60 hours
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Genetic variants in OCT1, CYP2C19, CYP2D6 and MAO A
Time Frame: Baseline
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Baseline
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Juergen Brockmoeller, Prof., University Medical Center Goettingen
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2013
Primary Completion (Actual)
February 1, 2016
Study Completion (Actual)
February 1, 2016
Study Registration Dates
First Submitted
January 30, 2014
First Submitted That Met QC Criteria
February 3, 2014
First Posted (Estimate)
February 4, 2014
Study Record Updates
Last Update Posted (Estimate)
May 12, 2016
Last Update Submitted That Met QC Criteria
May 11, 2016
Last Verified
May 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antimetabolites
- Adrenergic Agonists
- Micronutrients
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Serotonin 5-HT1 Receptor Agonists
- Serotonin Receptor Agonists
- Serotonin and Noradrenaline Reuptake Inhibitors
- Antidepressive Agents, Tricyclic
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Vitamins
- Reproductive Control Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Vitamin B Complex
- Antimalarials
- Adrenergic beta-2 Receptor Agonists
- Adrenergic beta-Agonists
- Tocolytic Agents
- Sympathomimetics
- Adrenergic Uptake Inhibitors
- Vasoconstrictor Agents
- Proguanil
- Amitriptyline
- Desvenlafaxine Succinate
- Thiamine
- Fenoterol
- Sumatriptan
Other Study ID Numbers
- PG-OCT
- 2012-003546-33 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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