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Drug Metabolism | Open Label Pharmacokinetic-Pharmacogenetic Study on Polymorphisms in the Organic Cation Transporter OCT1

Drug Metabolism research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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)

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Drug Metabolism

Membrane Transport

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Drug application AmitriptylineAmitriptyline: 25 mg, single oral application

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

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

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

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

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

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Drug application6 treatment periods. On each period one of the following interventions

Study Status

Completed

Start Date: April 2013

Completed Date: February 2016

Phase: Phase 1

Type: Interventional

Design:

Primary Outcome: Area under the plasma concentration-time curve (AUC) of the investigational drugs

Secondary Outcome: 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

Study sponsors, principal investigator, and references

Principal Investigator: Juergen Brockmoeller, Prof.

Lead Sponsor: University Medical Center Goettingen

Collaborator:

More information:https://clinicaltrials.gov/show/NCT02054299

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