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Open Label Pharmacokinetic-Pharmacogenetic Study on Polymorphisms in the Organic Cation Transporter OCT1 (PG-OCT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02054299
Recruitment Status : Completed
First Posted : February 4, 2014
Last Update Posted : May 12, 2016
Information provided by (Responsible Party):
Johannes Matthaei, University Medical Center Goettingen

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Drug Metabolism Membrane Transport Drug: Drug application Amitriptyline Drug: Drug application Desvenlafaxine Drug: Drug application Sumatriptan Drug: Drug application Proguanil Drug: Drug application Fenoterol Drug: Drug application Thiamine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effects of Genetic Polymorphisms in the Organic Cation Transporter OCT1 on Cellular Uptake and Metabolism of Antidepressants and Other Organic Cationic Drugs
Study Start Date : April 2013
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Arm Intervention/treatment
Experimental: Drug application
6 treatment periods. On each period one of the following interventions
Drug: Drug application Amitriptyline
Amitriptyline: 25 mg, single oral application

Drug: Drug application Desvenlafaxine
Desvenlafaxine: 50 mg, single oral application

Drug: Drug application Sumatriptan
Sumatriptan: 50 mg, single oral application

Drug: Drug application Proguanil
Proguanil: 200mg, single oral application

Drug: Drug application Fenoterol
Fenoterol: 180 mcg, single intravenous application

Drug: Drug application Thiamine
Thiamine: 200mg, single oral application

Primary Outcome Measures :
  1. Area under the plasma concentration-time curve (AUC) of the investigational drugs [ Time Frame: up to 60 hours ]

Secondary Outcome Measures :
  1. 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 ]
  2. Dry mouth, fatigue, nausea, headache, vertigo, tinnitus, chills, anxiety and difficulties to read on Visual Analog Scales. [ Time Frame: up to 60 hours ]
  3. Sedation on Stanford sedation scale [ Time Frame: up to 60 hours ]
  4. 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 ]
  5. Genetic variants in OCT1, CYP2C19, CYP2D6 and MAO A [ Time Frame: Baseline ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. 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.
  2. 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.
  3. Healthy adults aged ≥18 to < 50 years
  4. 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.
  5. Willingness to meet the study instructions and to co-operate with the study personal
  6. 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
  7. 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
  8. 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:

  1. Unwillingness or inability to give informed consent
  2. Involvement in the planning and conduct of the study (applies to staff directly employed at the study site / department)
  3. 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.
  4. Blood, plasma or thrombocyte donation during the last 15 days prior to application of the test drugs.
  5. Any planned surgical treatment during the last 14 days prior and 14 days after the application of the test drugs.
  6. Known pregnancy or lactation period
  7. 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.
  8. QTcF > 450 ms in screening ECG
  9. 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)
  10. Any disease affecting liver or kidney or impairment of the liver or kidney-function
  11. Any cardiovascular disease
  12. Moderate to severe hypertension requiring medication therapy
  13. Bronchogenic asthma requiring constant drug treatment (stages 2 to 4 asthma)
  14. Diabetes mellitus, hyperthyroidism, hypothyroidism
  15. Glaucoma
  16. Symptomatic prostatic hyperplasia
  17. Any medical constellation that increases risk of bleeding, including chronic treatment with NSAID or COX-2 inhibitors
  18. History of alcohol and/or drug abuse and/or any abusive use of medicaments and/or positive drug screen
  19. 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.
  20. Any major gastrointestinal disease and any gastrointestinal disorder that is expected to significantly interfere with the pharmacokinetics of the study drug
  21. Gastrointestinal surgery which may interfere with the pharmacokinetics of the study drug (except appendectomy or herniotomy)
  22. 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.
  23. Any other findings that could compromise the safety of the participant or the quality of the study-results
  24. Any known hypersensitivity or allergic reactions to any of the tested drugs
  25. History of severe hypersensitivity reactions and anaphylaxis
  26. Any other clinically significant diseases as judged by the investigator
  27. Body temperature > 37.5°C prior to drug application
  28. Known infection with HIV, Hepatitis B (HBsAg) or Hepatitis C (no laboratory diagnostics concerning these diseases will be performed within the present study)
  29. Inability or unwillingness to avoid any intake of alcohol from 48 h prior to until 72 hours after Investigational Medicinal Product (IMP) application application
  30. Pregnancy (positive pregnancy test performed prior to drug administration)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02054299

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Department of Clinical Pharmacology, University Medical Center Goettingen
Goettingen, Germany, 37075
Sponsors and Collaborators
University Medical Center Goettingen
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Study Director: Juergen Brockmoeller, Prof. University Medical Center Goettingen

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Johannes Matthaei, Sub-investigator, Principal investigator is Prof. Juergen Brockmoeller, University Medical Center Goettingen Identifier: NCT02054299    
Other Study ID Numbers: PG-OCT
2012-003546-33 ( EudraCT Number )
First Posted: February 4, 2014    Key Record Dates
Last Update Posted: May 12, 2016
Last Verified: May 2016
Additional relevant MeSH terms:
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Amitriptyline, perphenazine drug combination
Desvenlafaxine Succinate
Vasoconstrictor Agents
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents