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Drug MetabolismPhase 1PG-OCTNCT02054299

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

A Phase 1 study testing Drug application Amitriptyline, Drug application Desvenlafaxine and Drug application Sumatriptan in people with Drug Metabolism and Membrane Transport, run by University Medical Center Goettingen at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Drug Metabolism, Membrane Transport
What is being tested?
Drug application Amitriptyline, Drug application Desvenlafaxine and Drug application Sumatriptan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteGermany
Study dates
Apr 2013to Feb 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Department of Clinical Pharmacology, University Medical Center Goettingen

    Göttingen, 37075

Other trials in Germany

About this study

Official title: 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.

Being tested
Drug application Amitriptyline, Drug application Desvenlafaxine, Drug application Sumatriptan, Drug application Proguanil, Drug application Fenoterol

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Drug application AmitriptylineDrug

    Amitriptyline: 25 mg, single oral application

  • Drug application DesvenlafaxineDrug

    Desvenlafaxine: 50 mg, single oral application

  • Drug application SumatriptanDrug

    Sumatriptan: 50 mg, single oral application

  • Drug application ProguanilDrug

    Proguanil: 200mg, single oral application

  • Drug application FenoterolDrug

    Fenoterol: 180 mcg, single intravenous application

  • Drug application ThiamineDrug

    Thiamine: 200mg, single oral application

Study groups in NCT02054299
Study groupRoleWhat they receive
Drug applicationExperimental6 treatment periods. On each period one of the following interventions
Receives: Drug: Drug application Amitriptyline; Drug: Drug application Desvenlafaxine; Drug: Drug application Sumatriptan; Drug: Drug application Proguanil; Drug: Drug application Fenoterol; Drug: Drug application Thiamine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area under the plasma concentration-time curve (AUC) of the investigational drugs

    Measured: up to 60 hours

Secondary outcomes (5)

  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

    Measured: up to 60 hours

  2. Dry mouth, fatigue, nausea, headache, vertigo, tinnitus, chills, anxiety and difficulties to read on Visual Analog Scales.

    Measured: up to 60 hours

  3. Sedation on Stanford sedation scale

    Measured: 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

    Measured: up to 60 hours

  5. Genetic variants in OCT1, CYP2C19, CYP2D6 and MAO A

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2014 (estimated)
  2. Study startApr 2013
  3. Primary completionFeb 2016
  4. Study completionFeb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02054299
Sponsor's protocol ID
PG-OCT
Other IDs
2012-003546-33
Acronym
PG-OCT
Status last verified
May 2016
First submitted
30 Jan 2014
Last updated
12 May 2016
Results posted
No
Data monitoring committee
No

Publications

  • Tzvetkov MV, Matthaei J, Pojar S, Faltraco F, Vogler S, Prukop T, Seitz T, Brockmoller J. Increased Systemic Exposure and Stronger Cardiovascular and Metabolic Adverse Reactions to Fenoterol in Individuals with Heritable OCT1 Deficiency. Clin Pharmacol Ther. 2018 May;103(5):868-878. doi: 10.1002/cpt.812. Epub 2017 Dec 8.

    PubMed 28791698

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Drug application Amitriptyline, Drug application Desvenlafaxine and Drug application Sumatriptan in people with Drug Metabolism and Membrane Transport, run by University Medical Center Goettingen at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under the plasma concentration-time curve (AUC) of the investigational drugs (time frame: up to 60 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02054299, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2016.

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