Genotype-related Drug MetabolismPhase 1IKP243NCT01788254
Open Label Study for the Functional Characterization of Drug Metabolism and Transport
A Phase 1 study testing Codeine, Midazolam and pravastatin in people with Genotype-related Drug Metabolism, run by Matthias Schwab at 2 sites in Germany.
Trial summary
Aim of this study is to comprehensively assess in healthy volunteers the metabolic processes and factors that define drug response. Sources of variability are to be investigated and factors that can alter the hepatic metabolism and the pharmacokinetics of drugs shall be quantified. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Genotype-related Drug Metabolism
- What is being tested?
- Codeine, Midazolam and pravastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 2 sitesGermany
- Study dates
- Jan 2012to May 2015
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent obtained prior to study entry including informed consent for genetic research
- Both genders (male and female)
- Healthy adults aged ≥18 to <65 years
- Bodyweight not less than 48 kg and not more than 120 kg. BMI not less than 18 kg/m² and not greater than 33 kg/m².
- Smokers and nonsmokers. Smoking siblings will only be included if both siblings are smoking to a similar extend (+/- 10 cigarettes per day)
- healthy volunteers
- Dizygotic twins will only be included if both siblings are of the same gender, either male or female and triplets, quadruplets or other multiplets if at least two siblings of the same gender are considered.
Who cannot join
- Participation in a clinical trial involving the administration of medicines during the last 30 days 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 30 days prior to application of the test drugs.
- Pregnancy or lactation period
- Any relevant clinical and pathological findings at physical examination, ECG, taking blood pressure or in clinical chemistry tests (deviation of more than 10% of the normal range).
- Positive signal from urinary drug test
- Raynaud's syndrome
Show all 11Show fewer
- Taking any medication within 7 days before or during the trial with the following exceptions: Single doses of mild analgesics (e.g. aspirin, paracetamol, ibuprofen) an oral contraceptives.
- History of severe hypersensitivity reactions and anaphylaxis.
- History of intolerance or allergic reactions to or contraindication for any of the investigational products.
- Clinically significant diseases as judged by the investigator.
- Contraindication against MRI.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Stuttgart, 70376
Abteilung Klinische Pharmakologie
Tübingen, 72076
About this study
Aim of this study is to comprehensively assess in healthy volunteers the metabolic processes and factors that define drug response. Sources of variability are to be investigated and factors that can alter the hepatic metabolism and the pharmacokinetics of drugs shall be quantified.
Determination of variability is important when the pharmacokinetics of new drugs is being investigated and when the concept of individualized medicine is to be further developed. It is important to identify and differentiate between pharmaceutical, physiological (e.g. liver blood flow, renal function), environmental (e.g. foods and lifestyle), and genetic sources of inter-individual variability. For instance, inaccurate or false conclusions may be drawn from a single pharmacokinetic study, if the investigated medicine is metabolized by an enzyme with large inter-individual variability. Knowing the causes of variability and of the quantitative contribution of various processes might help to improve the oral formulations of drugs, might help selecting the right preclinical tests and selection criteria during clinical development, provide the basis to understand the influence of disease and to optimize established drug treatments in order to make future drug treatment safer and more efficient.
This study is designed as an add-on to the study "TWINS: Open Label Repeated Dose Study for the Evaluation of Heritability of and Genetic Influences on Drug Pharmacokinetics" (Eudra-CT: 2008-006223-31). Twins are not a random sample of the population, and they differ in their developmental environment. In this sense they are not representative for the population Thus, the results of TWINS cannot be automatically generalized but instead require validation in a representative population sample. While both studies assess pharmacologic factors important for drug response, TWINS contributes in particular data on the heritability of these processes.
- Conditions
- Genotype-related Drug Metabolism
- Being tested
- Codeine, Midazolam, pravastatin, Talinolol, torsemide
- Keywords
- pharmacokinetic/genetic, Cyp450 polymorphisms, Noninvasive functional characterization of liver heart and kidneys using MRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CodeineDrug
A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).
MidazolamDrug
A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).
pravastatinDrug
A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).
TalinololDrug
A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).
torsemideDrug
A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).
| Study group | Role | What they receive |
|---|---|---|
| Drug cocktail | Experimental | A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail). Receives: Drug: Codeine; Drug: Midazolam; Drug: pravastatin; Drug: Talinolol; Drug: torsemide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood levels and clearance (dose/AUC) of midazolam
Measured: 8 hours
Blood levels and clearance (dose/AUC) of torsemide
Measured: 8h
Blood levels and clearance (dose/AUC) of codeine
Measured: 8h
Blood levels and clearance (dose/AUC) of talinolol
Measured: 8h
Blood levels and clearance (dose/AUC) of pravastatin
Measured: 8h
Secondary outcomes (1)
determine metabolite profile
To determine metabolite profile of the phenotyping probes and to assess Pharmacokinetic parameters and/or metabolic ratios in relation to underlying genotypes as well as to validate the heritability estimates derived from TWINS.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2013 (estimated)
- Study startJan 2012
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Genotype-related Drug MetabolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matthias Schwab
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Matthias Schwab, University Hospital Tuebingen
- Investigators
- Matthias Schwab, Prof., M.D., Principal investigator, Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology and University of Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01788254
- Sponsor's protocol ID
- IKP243
- Other IDs
- 2011-002291-16
- Acronym
- IKP243
- Status last verified
- May 2015
- First submitted
- 31 Jan 2013
- Last updated
- 27 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Study for the Functional Characterization of Drug Metabolism and Transport
- ClinicalTrials.gov ID
- NCT01788254
- Acronym / sponsor ID
- IKP243 / IKP243
- Conditions
- Genotype-related Drug Metabolism
- Keywords
- pharmacokinetic/genetic, Cyp450 polymorphisms, Noninvasive functional characterization of liver heart and kidneys using MRI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Matthias SchwabUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 11 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim of this study is to comprehensively assess in healthy volunteers the metabolic processes and factors that define drug response. Sources of variability are to be investigated and factors that can alter the hepatic metabolism and the pharmacokinetics of drugs shall be quantified.
Determination of variability is important when the pharmacokinetics of new drugs is being investigated and when the concept of individualized medicine is to be further developed. It is important to identify and differentiate between pharmaceutical, physiological (e.g. liver blood flow, renal function), environmental (e.g. foods and lifestyle), and genetic sources of inter-individual variability. For instance, inaccurate or false conclusions may be drawn from a single pharmacokinetic study, if the investigated medicine is metabolized by an enzyme with large inter-individual variability. Knowing the causes of variability and of the quantitative contribution of various processes might help to improve the oral formulations of drugs, might help selecting the right preclinical tests and selection criteria during clinical development, provide the basis to understand the influence of disease and to optimize established drug treatments in order to make future drug treatment safer and more efficient.
This study is designed as an add-on to the study "TWINS: Open Label Repeated Dose Study for the Evaluation of Heritability of and Genetic Influences on Drug Pharmacokinetics" (Eudra-CT: 2008-006223-31). Twins are not a random sample of the population, and they differ in their developmental environment. In this sense they are not representative for the population Thus, the results of TWINS cannot be automatically generalized but instead require validation in a representative population sample. While both studies assess pharmacologic factors important for drug response, TWINS contributes in particular data on the heritability of these processes.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug cocktail | Experimental | Drug: Codeine, Drug: Midazolam, Drug: pravastatin, Drug: Talinolol, Drug: torsemideA single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Written informed consent obtained prior to study entry including informed consent for genetic research
- Both genders (male and female)
- Healthy adults aged ≥18 to <65 years
- Bodyweight not less than 48 kg and not more than 120 kg. BMI not less than 18 kg/m² and not greater than 33 kg/m².
- Smokers and nonsmokers. Smoking siblings will only be included if both siblings are smoking to a similar extend (+/- 10 cigarettes per day)
Key exclusion criteria (11 listed)
- Participation in a clinical trial involving the administration of medicines during the last 30 days 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 30 days prior to application of the test drugs.
- Pregnancy or lactation period
- Any relevant clinical and pathological findings at physical examination, ECG, taking blood pressure or in clinical chemistry tests (deviation of more than 10% of the normal range).
- Positive signal from urinary drug test
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CodeineA single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail). | Drug | Drug cocktail |
| MidazolamA single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail). | Drug | Drug cocktail |
| pravastatinA single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail). | Drug | Drug cocktail |
| TalinololA single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail). | Drug | Drug cocktail |
| torsemideA single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail). | Drug | Drug cocktail |
Primary outcome
Blood levels and clearance (dose/AUC) of midazolam
Time frame: 8 hours
Blood levels and clearance (dose/AUC) of torsemide
Time frame: 8h
Blood levels and clearance (dose/AUC) of codeine
Time frame: 8h
Blood levels and clearance (dose/AUC) of talinolol
Time frame: 8h
Blood levels and clearance (dose/AUC) of pravastatin
Time frame: 8h
1 secondary outcome
determine metabolite profile
Time frame: 8 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias Schwab, Prof., M.D. principal investigator
Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology and University of Tuebingen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Codeine, Midazolam and pravastatin in people with Genotype-related Drug Metabolism, run by Matthias Schwab at 2 sites 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 7 inclusion and 11 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 27 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Blood levels and clearance (dose/AUC) of midazolam (time frame: 8 hours). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 May 2015.